1268 Davila, A. M., Blachier, F., Gotteland, M., Andriamihaja, M., Benetti, P. H., Sanz, Y., & Tome, D. (2013). Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host. *Pharmacol Res*, *68*, 95-107.

1271 Dawson, L. F., Donahue, E. H., Cartman, S. T., Barton, R. H., Bundy, J., McNerney, R., Minton, N. P., & Wren, B. W. (2011). The analysis of para-cresol production and tolerance in *Clostridium difficile* 027 and 012 strains. *BMC Microbiol*, *11*, 86.

1275 De Preter, V., Geboes, K., Verbrugghe, K., De Vuyst, L., Vanhoutte, T., Huys, G., Swings, J., Pot, B., & Verbeke, K. (2004). The *in vivo* use of the stable isotope-labelled biomarkers lactose-[$^{15}$N]ureide and [$^{2}$H$_4$]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers. *Br J Nutr*, *92*, 439-446.

1280 De Preter, V., Hamer, H. M., Windey, K., & Verbeke, K. (2011). The impact of pre- and/or probiotics on human colonic metabolism: does it affect human health? *Mol Nutr Food Res*, *55*, 46-57.

1283 De Preter, V., Raemen, H., Cloetens, L., Houben, E., Rutgeerts, P., & Verbeke, K. (2008). Effect of dietary intervention with different pre- and probiotics on intestinal bacterial enzyme activities. *Eur J Clin Nutr*, *62*, 225-231.

1286 De Preter, V., Vanhoutte, T., Huys, G., Swings, J., De Vuyst, L., Rutgeerts, P., & Verbeke, K. (2007). Effects of *Lactobacillus casei Shirota*, *Bifidobacterium breve*, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans. *Am J Physiol Gastrointest Liver Physiol*, *292*, G358-368.

1290 Demigne, C., Morand, C., Levrat, M. A., Besson, C., Moundras, C., & Remesy, C. (1995). Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes. *Br J Nutr*, *74*, 209-219.
1268 Davila, A. M., Blachier, F., Gotteland, M., Andriamihaja, M., Benetti, P. H., Sanz, Y., & Tome, D. (2013). Intestinal luminal nitrogen metabolism: role of the gut microbiota and consequences for the host. *Pharmacol Res*, *68*, 95-107.

1271 Dawson, L. F., Donahue, E. H., Cartman, S. T., Barton, R. H., Bundy, J., McNerney, R., Minton, N. P., & Wren, B. W. (2011). The analysis of para-cresol production and tolerance in *Clostridium difficile* 027 and 012 strains. *BMC Microbiol*, *11*, 86.

1275 De Preter, V., Geboes, K., Verbrugghe, K., De Vuyst, L., Vanhoutte, T., Huys, G., Swings, J., Pot, B., & Verbeke, K. (2004). The *in vivo* use of the stable isotope-labelled biomarkers lactose-[$^{15}$N]ureide and [$^{2}$H$_4$]tyrosine to assess the effects of pro- and prebiotics on the intestinal flora of healthy human volunteers. *Br J Nutr*, *92*, 439-446.

1280 De Preter, V., Hamer, H. M., Windey, K., & Verbeke, K. (2011). The impact of pre- and/or probiotics on human colonic metabolism: does it affect human health? *Mol Nutr Food Res*, *55*, 46-57.

1283 De Preter, V., Raemen, H., Cloetens, L., Houben, E., Rutgeerts, P., & Verbeke, K. (2008). Effect of dietary intervention with different pre- and probiotics on intestinal bacterial enzyme activities. *Eur J Clin Nutr*, *62*, 225-231.

1286 De Preter, V., Vanhoutte, T., Huys, G., Swings, J., De Vuyst, L., Rutgeerts, P., & Verbeke, K. (2007). Effects of *Lactobacillus casei Shirota*, *Bifidobacterium breve*, and oligofructose-enriched inulin on colonic nitrogen-protein metabolism in healthy humans. *Am J Physiol Gastrointest Liver Physiol*, *292*, G358-368.

1290 Demigne, C., Morand, C., Levrat, M. A., Besson, C., Moundras, C., & Remesy, C. (1995). Effect of propionate on fatty acid and cholesterol synthesis and on acetate metabolism in isolated rat hepatocytes. *Br J Nutr*, *74*, 209-219.
1293 Diaz, E., Ferrandez, A., Prieto, M. A., & Garcia, J. L. (2001). Biodegradation of

1294 aromatic compounds by *Escherichia coli*. *Microbiol Mol Biol Rev*, *65*, 523-569,

1295 table of contents.

1296 Doerner, K. C., Mason, B. P., Kridelbaugh, D., & Loughrin, J. (2009). Fe(III) stimulates

1297 3-methylindole and 4-methylphenol production in swine lagoon enrichments and

1298 *Clostridium scatologenes* ATCC 25775. *Lett Appl Microbiol*, *48*, 118-124.

1299 EFSA Panel on Dietetic Products, N. a. A. (2012). Scientific Opinion on Dietary

1300 Reference Values for protein. *EFSA Journal*, *10*, 1-66.

1301 Eggeling, L., & Sahm, H. (2003). New ubiquitous translocators: amino acid export by

1302 *Corynebacterium glutamicum* and *Escherichia coli*. *Arch Microbiol*, *180*, 155-

1303 160.

1304 Eisenberg, T., Knauer, H., Schauer, A., Buttner, S., Ruckenstuhl, C., Carmona-

1305 Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., Fussi, H.,

1306 Deszcz, L., Hartl, R., Schraml, E., Criollo, A., Megalou, E., Weiskopf, D., Laun,

1307 P., Heeren, G., Breitenbach, M., Grubeck-Loebenstein, B., Herker, E.,

1308 Fahrenkrog, B., Frohlich, K. U., Sinner, F., Tavernarakis, N., Minois, N.,

1309 Kroemer, G., & Madeo, F. (2009). Induction of autophagy by spermidine

1310 promotes longevity. *Nat Cell Biol*, *11*, 1305-1314.

1311 Eklou-Lawson, M., Bernard, F., Neveux, N., Chaumontet, C., Bos, C., Davila-Gay, A.

1312 M., Tome, D., Cynober, L., & Blachier, F. (2009). Colonic luminal ammonia

1313 and portal blood L-glutamine and L-arginine concentrations: a possible link

1314 between colon mucosa and liver ureagenesis. *Amino Acids*, *37*, 751-760.

1315 El-Merahbi, R., Loffler, M., Mayer, A., & Sumara, G. (2015). The roles of peripheral

1316 serotonin in metabolic homeostasis. *FEBS Lett*, *589*, 1728-1734.
1293 Diaz, E., Ferrandez, A., Prieto, M. A., & Garcia, J. L. (2001). Biodegradation of

1294 aromatic compounds by *Escherichia coli*. *Microbiol Mol Biol Rev*, *65*, 523-569,

1295 table of contents.

1296 Doerner, K. C., Mason, B. P., Kridelbaugh, D., & Loughrin, J. (2009). Fe(III) stimulates

1297 3-methylindole and 4-methylphenol production in swine lagoon enrichments and

1298 *Clostridium scatologenes* ATCC 25775. *Lett Appl Microbiol*, *48*, 118-124.

1299 EFSA Panel on Dietetic Products, N. a. A. (2012). Scientific Opinion on Dietary

1300 Reference Values for protein. *EFSA Journal, 10*, 1-66.

1301 Eggeling, L., & Sahm, H. (2003). New ubiquitous translocators: amino acid export by

1302 *Corynebacterium glutamicum* and *Escherichia coli*. *Arch Microbiol*, *180*, 155-

1303 160.

1304 Eisenberg, T., Knauer, H., Schauer, A., Buttner, S., Ruckenstuhl, C., Carmona-

1305 Gutierrez, D., Ring, J., Schroeder, S., Magnes, C., Antonacci, L., Fussi, H.,

1306 Deszcz, L., Hartl, R., Schraml, E., Criollo, A., Megalou, E., Weiskopf, D., Laun,

1307 P., Heeren, G., Breitenbach, M., Grubeck-Loebenstein, B., Herker, E.,

1308 Fahrenkrog, B., Frohlich, K. U., Sinner, F., Tavernarakis, N., Minois, N.,

1309 Kroemer, G., & Madeo, F. (2009). Induction of autophagy by spermidine

1310 promotes longevity. *Nat Cell Biol*, *11*, 1305-1314.

1311 Eklou-Lawson, M., Bernard, F., Neveux, N., Chaumontet, C., Bos, C., Davila-Gay, A.

1312 M., Tome, D., Cynober, L., & Blachier, F. (2009). Colonic luminal ammonia

1313 and portal blood L-glutamine and L-arginine concentrations: a possible link

1314 between colon mucosa and liver ureagenesis. *Amino Acids*, *37*, 751-760.

1315 El-Merahbi, R., Loffler, M., Mayer, A., & Sumara, G. (2015). The roles of peripheral

1316 serotonin in metabolic homeostasis. *FEBS Lett*, *589*, 1728-1734.
1317 Evenepoel, P., Meijers, B. K., Bammens, B. R., & Verbeke, K. (2009). Uremic toxins
1318 originating from colonic microbial metabolism. *Kidney Int Suppl*, S12-19.

1319 Everard, A., Lazarevic, V., Gaia, N., Johansson, M., Stahlman, M., Backhed, F.,
1320 Delzenne, N. M., Schrenzel, J., Francois, P., & Cani, P. D. (2014). Microbiome
1321 of prebiotic-treated mice reveals novel targets involved in host response during
1322 obesity. *ISME J*, 8, 2116-2130.

1323 Feehily, C., & Karatzas, K. A. (2013). Role of glutamate metabolism in bacterial
1324 responses towards acid and other stresses. *J Appl Microbiol*, 114, 11-24.

1325 Ferrario, C., Duranti, S., Milani, C., Mancabelli, L., Lugli, G. A., Turroni, F.,
1326 Mangifesta, M., Viappiani, A., Ossiprandi, M. C., van Sinderen, D., & Ventura,
1327 M. (2015). Exploring Amino Acid Auxotrophy in *Bifidobacterium bifidum*
1328 PRL2010. *Front Microbiol*, 6, 1331.

1329 Fichman, Y., Gerdes, S. Y., Kovacs, H., Szabados, L., Zilberstein, A., & Csonka, L. N.
1330 (2014). Evolution of proline biosynthesis: enzymology, bioinformatics, genetics,
1331 and transcriptional regulation. *Biol Rev Camb Philos Soc*.

1332 Fischbach, M. A., & Sonnenburg, J. L. (2011). Eating for two: how metabolism
1333 establishes interspecies interactions in the gut. *Cell Host Microbe*, 10, 336-347.

1334 Flannigan, K. L., Agbor, T. A., Motta, J. P., Ferraz, J. G., Wang, R., Buret, A. G., &
1335 Wallace, J. L. (2015). Proresolution effects of hydrogen sulfide during colitis are
1336 mediated through hypoxia-inducible factor-1alpha. *FASEB J*, 29, 1591-1602.

1337 Fonknechten, N., Chaussonnerie, S., Tricot, S., Lajus, A., Andreesen, J. R., Perchat, N.,
1338 Pelletier, E., Gouyvenoux, M., Barbe, V., Salanoubat, M., Le Paslier, D.,
1339 Weissenbach, J., Cohen, G. N., & Kreimeyer, A. (2010). *Clostridium sticklandii*,
1340 a specialist in amino acid degradation: revisiting its metabolism through its
1341 genome sequence. *BMC Genomics*, 11, 555.
1317 Evenepoel, P., Meijers, B. K., Bammens, B. R., & Verbeke, K. (2009). Uremic toxins
1318 originating from colonic microbial metabolism. *Kidney Int Suppl*, S12-19.

1319 Everard, A., Lazarevic, V., Gaia, N., Johansson, M., Stahlman, M., Backhed, F.,
1320 Delzenne, N. M., Schrenzel, J., Francois, P., & Cani, P. D. (2014). Microbiome
1321 of prebiotic-treated mice reveals novel targets involved in host response during
1322 obesity. *ISME J*, 8, 2116-2130.

1323 Feehily, C., & Karatzas, K. A. (2013). Role of glutamate metabolism in bacterial
1324 responses towards acid and other stresses. *J Appl Microbiol*, 114, 11-24.

1325 Ferrario, C., Duranti, S., Milani, C., Mancabelli, L., Lugli, G. A., Turroni, F.,
1326 Mangifesta, M., Viappiani, A., Ossiprandi, M. C., van Sinderen, D., & Ventura,
1327 M. (2015). Exploring Amino Acid Auxotrophy in *Bifidobacterium bifidum*
1328 PRL2010. *Front Microbiol*, 6, 1331.

1329 Fichman, Y., Gerdes, S. Y., Kovacs, H., Szabados, L., Zilberstein, A., & Csonka, L. N.
1330 (2014). Evolution of proline biosynthesis: enzymology, bioinformatics, genetics,
1331 and transcriptional regulation. *Biol Rev Camb Philos Soc*.

1332 Fischbach, M. A., & Sonnenburg, J. L. (2011). Eating for two: how metabolism
1333 establishes interspecies interactions in the gut. *Cell Host Microbe*, 10, 336-347.

1334 Flannigan, K. L., Agbor, T. A., Motta, J. P., Ferraz, J. G., Wang, R., Buret, A. G., &
1335 Wallace, J. L. (2015). Proresolution effects of hydrogen sulfide during colitis are
1336 mediated through hypoxia-inducible factor-1alpha. *FASEB J*, 29, 1591-1602.

1337 Fonknechten, N., Chaussonnerie, S., Tricot, S., Lajus, A., Andreesen, J. R., Perchat, N.,
1338 Pelletier, E., Gouyvenoux, M., Barbe, V., Salanoubat, M., Le Paslier, D.,
1339 Weissenbach, J., Cohen, G. N., & Kreimeyer, A. (2010). *Clostridium sticklandii*,
1340 a specialist in amino acid degradation: revisiting its metabolism through its
1341 genome sequence. *BMC Genomics*, 11, 555.
1342 Fouque, D., Pelletier, S., Mafra, D., & Chauveau, P. (2011). Nutrition and chronic kidney disease. *Kidney Int*, *80*, 348-357.

1344 Freestone, P. (2013). Communication between bacteria and their hosts. *Scientifica* (Cairo), *2013*, 361073.

1346 Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., Takahashi, M., Fukuda, N. N., Murakami, S., Miyauchi, E., Hino, S., Atarashi, K., Onawa, S., Fujimura, Y., Lockett, T., Clarke, J. M., Topping, D. L., Tomita, M., Hori, S., Ohara, O., Morita, T., Koseki, H., Kikuchi, J., Honda, K., Hase, K., & Ohno, H. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. *Nature*, *504*, 446-450.

1353 Gamet, L., Cazenave, Y., Trocheris, V., Denis-Pouxviel, C., & Murat, J. C. (1991). Involvement of ornithine decarboxylase in the control of proliferation of the HT29 human colon cancer cell line. Effect of vasoactive intestinal peptide on enzyme activity. *Int J Cancer*, *47*, 633-638.

1357 Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J. (2009). Butyrate improves insulin sensitivity and increases energy expenditure in mice. *Diabetes*, *58*, 1509-1517.

1360 Geboes, K. P., De Hertogh, G., De Preter, V., Luypaerts, A., Bammens, B., Evenepoel, P., Ghoos, Y., Geboes, K., Rutgeerts, P., & Verbeke, K. (2006). The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon. *Br J Nutr*, *96*, 1078-1086.

1364 Geypens, B., Claus, D., Evenepoel, P., Hiele, M., Maes, B., Peeters, M., Rutgeerts, P., & Ghoos, Y. (1997). Influence of dietary protein supplements on the formation of bacterial metabolites in the colon. *Gut*, *41*, 70-76.
1342 Fouque, D., Pelletier, S., Mafra, D., & Chauveau, P. (2011). Nutrition and chronic kidney disease. *Kidney Int*, *80*, 348-357.

1344 Freestone, P. (2013). Communication between bacteria and their hosts. *Scientifica* (Cairo), 2013, 361073.

1346 Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., Takahashi, M., Fukuda, N. N., Murakami, S., Miyauchi, E., Hino, S., Atarashi, K., Onawa, S., Fujimura, Y., Lockett, T., Clarke, J. M., Topping, D. L., Tomita, M., Hori, S., Ohara, O., Morita, T., Koseki, H., Kikuchi, J., Honda, K., Hase, K., & Ohno, H. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. *Nature*, *504*, 446-450.

1353 Gamet, L., Cazenave, Y., Trocheris, V., Denis-Pouxviel, C., & Murat, J. C. (1991). Involvement of ornithine decarboxylase in the control of proliferation of the HT29 human colon cancer cell line. Effect of vasoactive intestinal peptide on enzyme activity. *Int J Cancer*, *47*, 633-638.

1357 Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J. (2009). Butyrate improves insulin sensitivity and increases energy expenditure in mice. *Diabetes*, *58*, 1509-1517.

1360 Geboes, K. P., De Hertogh, G., De Preter, V., Luypaerts, A., Bammens, B., Evenepoel, P., Ghoos, Y., Geboes, K., Rutgeerts, P., & Verbeke, K. (2006). The influence of inulin on the absorption of nitrogen and the production of metabolites of protein fermentation in the colon. *Br J Nutr*, *96*, 1078-1086.

1364 Geypens, B., Claus, D., Evenepoel, P., Hiele, M., Maes, B., Peeters, M., Rutgeerts, P., & Ghoos, Y. (1997). Influence of dietary protein supplements on the formation of bacterial metabolites in the colon. *Gut*, *41*, 70-76.
1367 Gill, S. R., Pop, M., Deboy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S.,

1368 Gordon, J. I., Relman, D. A., Fraser-Liggett, C. M., & Nelson, K. E. (2006).

1369 Metagenomic analysis of the human distal gut microbiome. *Science*, **312**, 1355-1359.

1370

1371 Godon, J. J., Delorme, C., Bardowski, J., Chopin, M. C., Ehrlich, S. D., & Renault, P.

1372 (1993). Gene inactivation in *Lactococcus lactis*: branched-chain amino acid

1373 biosynthesis. *J Bacteriol*, **175**, 4383-4390.

1374 Gostner, A., Blaut, M., Schaffer, V., Kozianowski, G., Theis, S., Klingeberg, M.,

1375 Dombrowski, Y., Martin, D., Ehrhardt, S., Taras, D., Schwiertz, A., Kleessen,

1376 B., Luhrs, H., Schauber, J., Dorbath, D., Menzel, T., & Scheppach, W. (2006).

1377 Effect of isomalt consumption on faecal microflora and colonic metabolism in

1378 healthy volunteers. *Br J Nutr*, **95**, 40-50.

1379 Gupta, N. K., Thaker, A. I., Kanuri, N., Riehl, T. E., Rowley, C. W., Stenson, W. F., &

1380 Ciorba, M. A. (2012). Serum analysis of tryptophan catabolism pathway:

1381 correlation with Crohn's disease activity. *Inflamm Bowel Dis*, **18**, 1214-1220.

1382 Halmos, E. P., & Gibson, P. R. (2015). Dietary management of IBD--insights and

1383 advice. *Nat Rev Gastroenterol Hepatol*, **12**, 133-146.

1384 Hamer, H. M., Jonkers, D., Venema, K., Vanhoutvin, S., Troost, F. J., & Brummer, R.

1385 J. (2008). Review article: the role of butyrate on colonic function. *Aliment

1386 *Pharmacol Ther*, **27**, 104-119.

1387 Hanfrey, C. C., Pearson, B. M., Hazeldine, S., Lee, J., Gaskin, D. J., Woster, P. M.,

1388 Phillips, M. A., & Michael, A. J. (2011). Alternative spermidine biosynthetic

1389 route is critical for growth of *Campylobacter jejuni* and is the dominant

1390 polyamine pathway in human gut microbiota. *J Biol Chem*, **286**, 43301-43312.
1367 Gill, S. R., Pop, M., Deboy, R. T., Eckburg, P. B., Turnbaugh, P. J., Samuel, B. S.,

1368 Gordon, J. I., Relman, D. A., Fraser-Liggett, C. M., & Nelson, K. E. (2006).

1369 Metagenomic analysis of the human distal gut microbiome. *Science*, **312**, 1355-1359.

1370

1371 Godon, J. J., Delorme, C., Bardowski, J., Chopin, M. C., Ehrlich, S. D., & Renault, P.

1372 (1993). Gene inactivation in *Lactococcus lactis*: branched-chain amino acid

1373 biosynthesis. *J Bacteriol*, **175**, 4383-4390.

1374 Gostner, A., Blaut, M., Schaffer, V., Kozianowski, G., Theis, S., Klingeberg, M.,

1375 Dombrowski, Y., Martin, D., Ehrhardt, S., Taras, D., Schwiertz, A., Kleessen,

1376 B., Luhrs, H., Schauber, J., Dorbath, D., Menzel, T., & Scheppach, W. (2006).

1377 Effect of isomalt consumption on faecal microflora and colonic metabolism in

1378 healthy volunteers. *Br J Nutr*, **95**, 40-50.

1379 Gupta, N. K., Thaker, A. I., Kanuri, N., Riehl, T. E., Rowley, C. W., Stenson, W. F., &

1380 Ciorba, M. A. (2012). Serum analysis of tryptophan catabolism pathway:

1381 correlation with Crohn's disease activity. *Inflamm Bowel Dis*, **18**, 1214-1220.

1382 Halmos, E. P., & Gibson, P. R. (2015). Dietary management of IBD--insights and

1383 advice. *Nat Rev Gastroenterol Hepatol*, **12**, 133-146.

1384 Hamer, H. M., Jonkers, D., Venema, K., Vanhoutvin, S., Troost, F. J., & Brummer, R.

1385 J. (2008). Review article: the role of butyrate on colonic function. *Aliment*

1386 *Pharmacol Ther*, **27**, 104-119.

1387 Hanfrey, C. C., Pearson, B. M., Hazeldine, S., Lee, J., Gaskin, D. J., Woster, P. M.,

1388 Phillips, M. A., & Michael, A. J. (2011). Alternative spermidine biosynthetic

1389 route is critical for growth of *Campylobacter jejuni* and is the dominant

1390 polyamine pathway in human gut microbiota. *J Biol Chem*, **286**, 43301-43312.
1391 Hart, A. R., Luben, R., Olsen, A., Tjonneland, A., Linseisen, J., Nagel, G., Berglund, G., Lindgren, S., Grip, O., Key, T., Appleby, P., Bergmann, M. M., Boeing, H., Hallmans, G., Danielsson, A., Palmqvist, R., Sjodin, H., Hagglund, G., Overvad, K., Palli, D., Masala, G., Riboli, E., Kennedy, H., Welch, A., Khaw, K. T., Day, N., & Bingham, S. (2008). Diet in the aetiology of ulcerative colitis: a European prospective cohort study. *Digestion, 77*, 57-64.

1397 Heinken, A., & Thiele, I. (2015). Systems biology of host-microbe metabolomics. *Wiley Interdiscip Rev Syst Biol Med, 7*, 195-219.

1399 Helling, R. B. (1994). Why does *Escherichia coli* have two primary pathways for synthesis of glutamate? *Journal of Bacteriology, 4664-4668*.

1401 Hughes, R., Kurth, M. J., McGilligan, V., McGlynn, H., & Rowland, I. (2008). Effect of colonic bacterial metabolites on Caco-2 cell paracellular permeability in vitro. *Nutr Cancer, 60*, 259-266.

1404 Hughes, R., Magee, E. A., & Bingham, S. (2000). Protein degradation in the large intestine: relevance to colorectal cancer. *Curr Issues Intest Microbiol, 1*, 51-58.

1406 Ijssennagger, N., Belzer, C., Hooiveld, G. J., Dekker, J., van Mil, S. W., Muller, M., Kleerebezem, M., & van der Meer, R. (2015). Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon. *Proc Natl Acad Sci U S A, 112*, 10038-10043.

1410 Irsfeld, M., Spadafore, M., & Pruss, B. M. (2013). beta-phenylethylamine, a small molecule with a large impact. *Webmedcentral, 4(9)*.

1412 Jantchou, P., Morois, S., Clavel-Chapelon, F., Boutron-Ruault, M. C., & Carbonnel, F. (2010). Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study. *Am J Gastroenterol, 105*, 2195-2201.
1391 Hart, A. R., Luben, R., Olsen, A., Tjonneland, A., Linseisen, J., Nagel, G., Berglund, G., Lindgren, S., Grip, O., Key, T., Appleby, P., Bergmann, M. M., Boeing, H., Hallmans, G., Danielsson, A., Palmqvist, R., Sjodin, H., Hagglund, G., Overvad, K., Palli, D., Masala, G., Riboli, E., Kennedy, H., Welch, A., Khaw, K. T., Day, N., & Bingham, S. (2008). Diet in the aetiology of ulcerative colitis: a European prospective cohort study. *Digestion, 77*, 57-64.

1397 Heinken, A., & Thiele, I. (2015). Systems biology of host-microbe metabolomics. *Wiley Interdiscip Rev Syst Biol Med, 7*, 195-219.

1399 Helling, R. B. (1994). Why does *Escherichia coli* have two primary pathways for synthesis of glutamate? *Journal of Bacteriology, 4664-4668*.

1401 Hughes, R., Kurth, M. J., McGilligan, V., McGlynn, H., & Rowland, I. (2008). Effect of colonic bacterial metabolites on Caco-2 cell paracellular permeability in vitro. *Nutr Cancer, 60*, 259-266.

1404 Hughes, R., Magee, E. A., & Bingham, S. (2000). Protein degradation in the large intestine: relevance to colorectal cancer. *Curr Issues Intest Microbiol, 1*, 51-58.

1406 Ijssennagger, N., Belzer, C., Hooiveld, G. J., Dekker, J., van Mil, S. W., Muller, M., Kleerebezem, M., & van der Meer, R. (2015). Gut microbiota facilitates dietary heme-induced epithelial hyperproliferation by opening the mucus barrier in colon. *Proc Natl Acad Sci U S A, 112*, 10038-10043.

1410 Irsfeld, M., Spadafore, M., & Pruss, B. M. (2013). beta-phenylethylamine, a small molecule with a large impact. *Webmedcentral, 4(9)*.

1412 Jantchou, P., Morois, S., Clavel-Chapelon, F., Boutron-Ruault, M. C., & Carbonnel, F. (2010). Animal protein intake and risk of inflammatory bowel disease: The E3N prospective study. *Am J Gastroenterol, 105*, 2195-2201.
1415 Jowett, S. L., Seal, C. J., Pearce, M. S., Phillips, E., Gregory, W., Barton, J. R., &

1416 Welfare, M. R. (2004). Influence of dietary factors on the clinical course of

1417 ulcerative colitis: a prospective cohort study. *Gut*, 53, 1479-1484.

1418 Juraschek, S. P., Appel, L. J., Anderson, C. A., & Miller, E. R., 3rd. (2013). Effect of a

1419 high-protein diet on kidney function in healthy adults: results from the

1420 OmniHeart trial. *Am J Kidney Dis*, 61, 547-554.

1421 Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2014).

1422 Data, information, knowledge and principle: back to metabolism in KEGG.

1423 *Nucleic Acids Res*, **42**, D199-205.

1424 Karatzas, K. A., Brennan, O., Heavin, S., Morrissey, J., & O'Byrne, C. P. (2010).

1425 Intracellular accumulation of high levels of gamma-aminobutyrate by *Listeria*

1426 *monocytogenes* 10403S in response to low pH: uncoupling of gamma-

1427 aminobutyrate synthesis from efflux in a chemically defined medium. *Appl*

1428 *Environ Microbiol*, **76**, 3529-3537.

1429 Kim, E., Coelho, D., & Blachier, F. (2013). Review of the association between meat

1430 consumption and risk of colorectal cancer. *Nutr Res*, **33**, 983-994.

1431 Kim, J., Hetzel, M., Boiangiu, C. D., & Buckel, W. (2004). Dehydration of (R)-2-

1432 hydroxyacyl-CoA to enoyl-CoA in the fermentation of alpha-amino acids by

1433 anaerobic bacteria. *FEMS Microbiol Rev*, **28**, 455-468.

1434 Kim, J. N., Henriksen, E. D., Cann, I. K., & Mackie, R. I. (2014). Nitrogen utilization

1435 and metabolism in *Ruminococcus albus* 8. *Appl Environ Microbiol*, **80**, 3095-

1436 3102.

1437 Koppe, L., Pillon, N. J., Vella, R. E., Croze, M. L., Pelletier, C. C., Chambert, S.,

1438 Massy, Z., Glorieux, G., Vanholder, R., Dugenet, Y., Soula, H. A., Fouque, D.,
1415 Jowett, S. L., Seal, C. J., Pearce, M. S., Phillips, E., Gregory, W., Barton, J. R., &

1416 Welfare, M. R. (2004). Influence of dietary factors on the clinical course of

1417 ulcerative colitis: a prospective cohort study. *Gut*, 53, 1479-1484.

1418 Juraschek, S. P., Appel, L. J., Anderson, C. A., & Miller, E. R., 3rd. (2013). Effect of a

1419 high-protein diet on kidney function in healthy adults: results from the

1420 OmniHeart trial. *Am J Kidney Dis*, 61, 547-554.

1421 Kanehisa, M., Goto, S., Sato, Y., Kawashima, M., Furumichi, M., & Tanabe, M. (2014).

1422 Data, information, knowledge and principle: back to metabolism in KEGG.

1423 *Nucleic Acids Res*, 42, D199-205.

1424 Karatzas, K. A., Brennan, O., Heavin, S., Morrissey, J., & O'Byrne, C. P. (2010).

1425 Intracellular accumulation of high levels of gamma-aminobutyrate by *Listeria*

1426 *monocytogenes* 10403S in response to low pH: uncoupling of gamma-

1427 aminobutyrate synthesis from efflux in a chemically defined medium. *Appl*

1428 *Environ Microbiol*, 76, 3529-3537.

1429 Kim, E., Coelho, D., & Blachier, F. (2013). Review of the association between meat

1430 consumption and risk of colorectal cancer. *Nutr Res*, 33, 983-994.

1431 Kim, J., Hetzel, M., Boiangiu, C. D., & Buckel, W. (2004). Dehydration of (R)-2-

1432 hydroxyacyl-CoA to enoyl-CoA in the fermentation of alpha-amino acids by

1433 anaerobic bacteria. *FEMS Microbiol Rev*, 28, 455-468.

1434 Kim, J. N., Henriksen, E. D., Cann, I. K., & Mackie, R. I. (2014). Nitrogen utilization

1435 and metabolism in *Ruminococcus albus* 8. *Appl Environ Microbiol*, 80, 3095-

1436 3102.

1437 Koppe, L., Pillon, N. J., Vella, R. E., Croze, M. L., Pelletier, C. C., Chambert, S.,

1438 Massy, Z., Glorieux, G., Vanholder, R., Dugenet, Y., Soula, H. A., Fouque, D.,
1439 & Soulage, C. O. (2013). p-Cresyl sulfate promotes insulin resistance associated
1440 with CKD. *J Am Soc Nephrol*, 24, 88-99.

1441 Kredich, N. M. (1996). Biosynthesis of cysteine. In F. C. Neidhardt, Curtiss II, J. L.
1442 Ingraham, E. C. C. Lin, B. L. Low, B. Magasanik, W. S. Reznikoff, M. Riley,
1443 M. Schaechter & J. E. Umbarger (Eds.), *Escherichia coli and Salmonella:
cellular and molecular biology* (2nd ed., pp. 514-527). Washington, D. C.: ASM
1444 Press.

1446 Kulis-Horn, R. K., Persicke, M., & Kalinowski, J. (2014). Histidine biosynthesis, its
1447 regulation and biotechnological application in *Corynebacterium glutamicum*.
1448 *Microb Biotechnol*, 7, 5-25.

1449 Kuroda, M., Ohta, T., Uchiyama, I., Baba, T., Yuzawa, H., Kobayashi, I., Cui, L.,
1450 Oguchi, A., Aoki, K., Nagai, Y., Lian, J., Ito, T., Kanamori, M., Matsumaru, H.,
1451 Maruyama, A., Murakami, H., Hosoyama, A., Mizutani-Ui, Y., Takahashi, N.
1452 K., Sawano, T., Inoue, R., Kaito, C., Sekimizu, K., Hirakawa, H., Kuhara, S.,
1453 Goto, S., Yabuzaki, J., Kanehisa, M., Yamashita, A., Oshima, K., Furuya, K.,
1454 Yoshino, C., Shiba, T., Hattori, M., Ogasawara, N., Hayashi, H., & Hiramatsu,
1455 K. (2001). Whole genome sequencing of meticillin-resistant *Staphylococcus
1456 aureus*. *Lancet*, 357, 1225-1240.

1457 Lan, A., Andriamihaja, M., Blouin, J. M., Liu, X., Descatoire, V., Desclee de
1458 Maredsous, C., Davila, A. M., Walker, F., Tome, D., & Blachier, F. (2015).
1459 High-protein diet differently modifies intestinal goblet cell characteristics and
1460 mucosal cytokine expression in ileum and colon. *J Nutr Biochem*, 26, 91-98.

1461 Landete, J. M., Arena, M. E., Pardo, I., Manca de Nadra, M. C., & Ferrer, S. (2008).
1462 Comparative survey of putrescine production from agmatine deamination in
1463 different bacteria. *Food Microbiol*, 25, 882-887.
1439 & Soulage, C. O. (2013). p-Cresyl sulfate promotes insulin resistance associated
1440 with CKD. *J Am Soc Nephrol*, 24, 88-99.

1441 Kredich, N. M. (1996). Biosynthesis of cysteine. In F. C. Neidhardt, Curtiss II, J. L.
1442 Ingraham, E. C. C. Lin, B. L. Low, B. Magasanik, W. S. Reznikoff, M. Riley,
1443 M. Schaechter & J. E. Umbarger (Eds.), *Escherichia coli and Salmonella:
cellular and molecular biology* (2nd ed., pp. 514-527). Washington, D. C.: ASM
1444 Press.

1446 Kulis-Horn, R. K., Persicke, M., & Kalinowski, J. (2014). Histidine biosynthesis, its
1447 regulation and biotechnological application in *Corynebacterium glutamicum*.
1448 *Microb Biotechnol*, 7, 5-25.

1449 Kuroda, M., Ohta, T., Uchiyama, I., Baba, T., Yuzawa, H., Kobayashi, I., Cui, L.,
1450 Oguchi, A., Aoki, K., Nagai, Y., Lian, J., Ito, T., Kanamori, M., Matsumaru, H.,
1451 Maruyama, A., Murakami, H., Hosoyama, A., Mizutani-Ui, Y., Takahashi, N.
1452 K., Sawano, T., Inoue, R., Kaito, C., Sekimizu, K., Hirakawa, H., Kuhara, S.,
1453 Goto, S., Yabuzaki, J., Kanehisa, M., Yamashita, A., Oshima, K., Furuya, K.,
1454 Yoshino, C., Shiba, T., Hattori, M., Ogasawara, N., Hayashi, H., & Hiramatsu,
1455 K. (2001). Whole genome sequencing of meticillin-resistant *Staphylococcus
1456 aureus*. *Lancet*, 357, 1225-1240.

1457 Lan, A., Andriamihaja, M., Blouin, J. M., Liu, X., Descatoire, V., Desclee de
1458 Maredsous, C., Davila, A. M., Walker, F., Tome, D., & Blachier, F. (2015).
1459 High-protein diet differently modifies intestinal goblet cell characteristics and
1460 mucosal cytokine expression in ileum and colon. *J Nutr Biochem*, 26, 91-98.

1461 Landete, J. M., Arena, M. E., Pardo, I., Manca de Nadra, M. C., & Ferrer, S. (2008).
1462 Comparative survey of putrescine production from agmatine deamination in
1463 different bacteria. *Food Microbiol*, 25, 882-887.
1464 Landete, J. M., De las Rivas, B., Marcobal, A., & Munoz, R. (2008). Updated molecular knowledge about histamine biosynthesis by bacteria. *Crit Rev Food Sci Nutr, 48*, 697-714.

1467 Laparra, J. M., & Sanz, Y. (2010). Interactions of gut microbiota with functional food components and nutraceuticals. *Pharmacol Res, 61*, 219-225.

1469 Le Gall, G., Noor, S. O., Ridgway, K., Scovell, L., Jamieson, C., Johnson, I. T., Colquhoun, I. J., Kemsley, E. K., & Narbad, A. (2011). Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. *J Proteome Res, 10*, 4208-4218.

1473 Lecerf, J. M., Depeint, F., Clerc, E., Dugenet, Y., Niamba, C. N., Rhazi, L., Cayzeele, A., Abdelnour, G., Jaruga, A., Younes, H., Jacobs, H., Lambrey, G., Abdelnour, A. M., & Pouillart, P. R. (2012). Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties. *Br J Nutr*, 108, 1847-1858.

1479 Lee, J., Sperandio, V., Frantz, D. E., Longgood, J., Camilli, A., Phillips, M. A., & Michael, A. J. (2009). An alternative polyamine biosynthetic pathway is widespread in bacteria and essential for biofilm formation in *Vibrio cholerae*. *J Biol Chem*, 284, 9899-9907.

1483 Leschelle, X., Goubern, M., Andriamihaja, M., Blottiere, H. M., Couplan, E., Gonzalez-Barroso, M. D., Petit, C., Pagniez, A., Chaumontet, C., Mignotte, B., Bouillaud, F., & Blachier, F. (2005). Adaptative metabolic response of human colonic epithelial cells to the adverse effects of the luminal compound sulfide. *Biochim Biophys Acta*, 1725, 201-212.
1464 Landete, J. M., De las Rivas, B., Marcobal, A., & Munoz, R. (2008). Updated molecular knowledge about histamine biosynthesis by bacteria. *Crit Rev Food Sci Nutr, 48*, 697-714.

1467 Laparra, J. M., & Sanz, Y. (2010). Interactions of gut microbiota with functional food components and nutraceuticals. *Pharmacol Res, 61*, 219-225.

1469 Le Gall, G., Noor, S. O., Ridgway, K., Scovell, L., Jamieson, C., Johnson, I. T., Colquhoun, I. J., Kemsley, E. K., & Narbad, A. (2011). Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. *J Proteome Res, 10*, 4208-4218.

1473 Lecerf, J. M., Depeint, F., Clerc, E., Dugenet, Y., Niamba, C. N., Rhazi, L., Cayzeele, A., Abdelnour, G., Jaruga, A., Younes, H., Jacobs, H., Lambrey, G., Abdelnour, A. M., & Pouillart, P. R. (2012). Xylo-oligosaccharide (XOS) in combination with inulin modulates both the intestinal environment and immune status in healthy subjects, while XOS alone only shows prebiotic properties. *Br J Nutr*, 108, 1847-1858.

1479 Lee, J., Sperandio, V., Frantz, D. E., Longgood, J., Camilli, A., Phillips, M. A., & Michael, A. J. (2009). An alternative polyamine biosynthetic pathway is widespread in bacteria and essential for biofilm formation in *Vibrio cholerae*. *J Biol Chem, 284*, 9899-9907.

1483 Leschelle, X., Goubern, M., Andriamihaja, M., Blottiere, H. M., Couplan, E., Gonzalez-Barroso, M. D., Petit, C., Pagniez, A., Chaumontet, C., Mignotte, B., Bouillaud, F., & Blachier, F. (2005). Adaptative metabolic response of human colonic epithelial cells to the adverse effects of the luminal compound sulfide. *Biochim Biophys Acta*, 1725, 201-212.
1488 Linares, D. M., Fernandez, M., Martin, M. C., & Alvarez, M. A. (2009). Tyramine

1489 biosynthesis in *Enterococcus durans* is transcriptionally regulated by the

1490 extracellular pH and tyrosine concentration. *Microb Biotechnol*, 2, 625-633.

1491 Liu, M., Bayjanov, J. R., Renckens, B., Nauta, A., & Siezen, R. J. (2010). The

1492 proteolytic system of lactic acid bacteria revisited: a genomic comparison. *BMC*

1493 *Genomics*, 11, 36.

1494 Liu, X., Blouin, J. M., Santacruz, A., Lan, A., Andriamihaja, M., Wilkanowicz, S.,

1495 Benetti, P. H., Tome, D., Sanz, Y., Blachier, F., & Davila, A. M. (2014). High-

1496 protein diet modifies colonic microbiota and luminal environment but not

1497 colonocyte metabolism in the rat model: the increased luminal bulk connection.

1498 *Am J Physiol Gastrointest Liver Physiol*, 307, G459-470.

1499 Liu, Y., White, R. H., & Whitman, W. B. (2010). Methanococci use the

1500 diaminopimelate aminotransferase (DapL) pathway for lysine biosynthesis. *J*

1501 *Bacteriol*, 192, 3304-3310.

1502 Macfarlane, G. T., Cummings, J. H., & Allison, C. (1986). Protein degradation by

1503 human intestinal bacteria. *J Gen Microbiol*, 132, 1647-1656.

1504 Macfarlane, G. T., Cummings, J. H., Macfarlane, S., & Gibson, G. R. (1989). Influence

1505 of retention time on degradation of pancreatic enzymes by human colonic

1506 bacteria grown in a 3-stage continuous culture system. *J Appl Bacteriol*, 67, 520-

1507 527.

1508 Macfarlane, G. T., Gibson, G. R., & Cummings, J. H. (1992). Comparison of

1509 fermentation reactions in different regions of the human colon. *J Appl Bacteriol*,

1510 72, 57-64.

1511 Macfarlane, G. T., & Macfarlane, S. (2012). Bacteria, colonic fermentation, and

1512 gastrointestinal health. *J AOAC Int*, 95, 50-60.
1488 Linares, D. M., Fernandez, M., Martin, M. C., & Alvarez, M. A. (2009). Tyramine

1489 biosynthesis in *Enterococcus durans* is transcriptionally regulated by the

1490 extracellular pH and tyrosine concentration. *Microb Biotechnol*, 2, 625-633.

1491 Liu, M., Bayjanov, J. R., Renckens, B., Nauta, A., & Siezen, R. J. (2010). The

1492 proteolytic system of lactic acid bacteria revisited: a genomic comparison. *BMC*

1493 *Genomics*, 11, 36.

1494 Liu, X., Blouin, J. M., Santacruz, A., Lan, A., Andriamihaja, M., Wilkanowicz, S.,

1495 Benetti, P. H., Tome, D., Sanz, Y., Blachier, F., & Davila, A. M. (2014). High-

1496 protein diet modifies colonic microbiota and luminal environment but not

1497 colonocyte metabolism in the rat model: the increased luminal bulk connection.

1498 *Am J Physiol Gastrointest Liver Physiol*, 307, G459-470.

1499 Liu, Y., White, R. H., & Whitman, W. B. (2010). Methanococci use the

1500 diaminopimelate aminotransferase (DapL) pathway for lysine biosynthesis. *J*

1501 *Bacteriol*, 192, 3304-3310.

1502 Macfarlane, G. T., Cummings, J. H., & Allison, C. (1986). Protein degradation by

1503 human intestinal bacteria. *J Gen Microbiol*, 132, 1647-1656.

1504 Macfarlane, G. T., Cummings, J. H., Macfarlane, S., & Gibson, G. R. (1989). Influence

1505 of retention time on degradation of pancreatic enzymes by human colonic

1506 bacteria grown in a 3-stage continuous culture system. *J Appl Bacteriol*, 67, 520-

1507 527.

1508 Macfarlane, G. T., Gibson, G. R., & Cummings, J. H. (1992). Comparison of

1509 fermentation reactions in different regions of the human colon. *J Appl Bacteriol*,

1510 72, 57-64.

1511 Macfarlane, G. T., & Macfarlane, S. (2012). Bacteria, colonic fermentation, and

1512 gastrointestinal health. *J AOAC Int*, 95, 50-60.
1513 Magee, E. A., Richardson, C. J., Hughes, R., & Cummings, J. H. (2000). Contribution of dietary protein to sulfide production in the large intestine: an *in vitro* and a controlled feeding study in humans. *Am J Clin Nutr*, 72, 1488-1494.

1516 Marc, F., Weigel, P., C., L., Almeras, Y., M., S., Glansdorff, N., & Sakanyan, V. (2000). Characterization and kinetic mechanism of mono- and bifunctional ornithine acetyltransferases from thermophilic microorganisms. *Eur J Biochem*, 267, 5217-5226.

1520 Marckmann, P., Osther, P., Pedersen, A. N., & Jespersen, B. (2015). High-protein diets and renal health. *J Ren Nutr*, 25, 1-5.

1522 Marcobal, A., De las Rivas, B., Landete, J. M., Tabera, L., & Munoz, R. (2012). Tyramine and phenylethylamine biosynthesis by food bacteria. *Crit Rev Food Sci Nutr*, 52, 448-467.

1525 Mayeur, C., Veuillet, G., Michaud, M., Raul, F., Blottiere, H. M., & Blachier, F. (2005). Effects of agmatine accumulation in human colon carcinoma cells on polyamine metabolism, DNA synthesis and the cell cycle. *Biochim Biophys Acta*, 1745, 111-123.

1529 McIntosh, G. H., & Le Leu, R. K. (2001). The influence of dietary proteins on colon cancer risk. *Nutr Res*, 21, 1053-1066.

1531 Meijers, B. K., & Evenepoel, P. (2011). The gut-kidney axis: indoxyl sulfate, *p*-cresyl sulfate and CKD progression. *Nephrol Dial Transplant*, 26, 759-761.

1533 Metges, C. C. (2000). Contribution of microbial amino acids to amino acid homeostasis of the host. *J Nutr*, 130, 1857S-1864S.

1535 Meyer, T. W., & Hostetter, T. H. (2012). Uremic solutes from colon microbes. *Kidney Int*, 81, 949-954.
1513 Magee, E. A., Richardson, C. J., Hughes, R., & Cummings, J. H. (2000). Contribution of dietary protein to sulfide production in the large intestine: an *in vitro* and a controlled feeding study in humans. *Am J Clin Nutr*, 72, 1488-1494.

1516 Marc, F., Weigel, P., C., L., Almeras, Y., M., S., Glansdorff, N., & Sakanyan, V. (2000). Characterization and kinetic mechanism of mono- and bifunctional ornithine acetyltransferases from thermophilic microorganisms. *Eur J Biochem*, 267, 5217-5226.

1520 Marckmann, P., Osther, P., Pedersen, A. N., & Jespersen, B. (2015). High-protein diets and renal health. *J Ren Nutr*, 25, 1-5.

1522 Marcobal, A., De las Rivas, B., Landete, J. M., Tabera, L., & Munoz, R. (2012). Tyramine and phenylethylamine biosynthesis by food bacteria. *Crit Rev Food Sci Nutr*, 52, 448-467.

1525 Mayeur, C., Veuillet, G., Michaud, M., Raul, F., Blottiere, H. M., & Blachier, F. (2005). Effects of agmatine accumulation in human colon carcinoma cells on polyamine metabolism, DNA synthesis and the cell cycle. *Biochim Biophys Acta*, 1745, 111-123.

1529 McIntosh, G. H., & Le Leu, R. K. (2001). The influence of dietary proteins on colon cancer risk. *Nutr Res*, 21, 1053-1066.

1531 Meijers, B. K., & Evenepoel, P. (2011). The gut-kidney axis: indoxyl sulfate, *p*-cresyl sulfate and CKD progression. *Nephrol Dial Transplant*, 26, 759-761.

1533 Metges, C. C. (2000). Contribution of microbial amino acids to amino acid homeostasis of the host. *J Nutr*, 130, 1857S-1864S.

1535 Meyer, T. W., & Hostetter, T. H. (2012). Uremic solutes from colon microbes. *Kidney Int*, 81, 949-954.
1537 Millichap, J. G., & Yee, M. M. (2003). The diet factor in pediatric and adolescent
1538 migraine. *Pediatr Neurol*, 28, 9-15.

1539 Mimoun, S., Andriamihaja, M., Chaumontet, C., Atanasiu, C., Benamouzig, R., Blouin,
1540 J. M., Tome, D., Bouillaud, F., & Blachier, F. (2012). Detoxification of H₂S by
1541 differentiated colonic epithelial cells: implication of the sulfide oxidizing unit
1542 and of the cell respiratory capacity. *Antioxid Redox Signal*, 17, 1-10.

1543 Min, B., Pelaschier, J. T., Graham, D. E., Tumbula-Hansen, D., & Soll, D. (2002).
1544 Transfer RNA-dependent amino acid biosynthesis: an essential route to
1545 asparagine formation. *Proc Natl Acad Sci U S A*, 99, 2678-2683.

1546 Minguet, E. G., Vera-Sirera, F., Marina, A., Carbonell, J., & Blazquez, M. A. (2008).
1547 Evolutionary diversification in polyamine biosynthesis. *Mol Biol Evol*, 25, 2119-
1548 2128.

1549 Molenaar, D., Bosscher, J. S., ten Brink, B., Driessen, A. J., & Konings, W. N. (1993).
1550 Generation of a proton motive force by histidine decarboxylation and
1551 electrogenic histidine/histamine antiport in *Lactobacillus buchneri*. *J Bacteriol*,
1552 175, 2864-2870.

1553 Mouille, B., Delpal, S., Mayeur, C., & Blachier, F. (2003). Inhibition of human colon
carcinoma cell growth by ammonia: a non-cytotoxic process associated with
polyamine synthesis reduction. *Biochim Biophys Acta*, 1624, 88-97.

1556 Mouille, B., Robert, V., & Blachier, F. (2004). Adaptive increase of ornithine
1557 production and decrease of ammonia metabolism in rat colonocytes after
1558 hyperproteic diet ingestion. *Am J Physiol Gastrointest Liver Physiol*, 287, G344-
1559 351.
1537 Millichap, J. G., & Yee, M. M. (2003). The diet factor in pediatric and adolescent
1538 migraine. *Pediatr Neurol*, *28*, 9-15.

1539 Mimoun, S., Andriamihaja, M., Chaumontet, C., Atanasiu, C., Benamouzig, R., Blouin,
1540 J. M., Tome, D., Bouillaud, F., & Blachier, F. (2012). Detoxification of H₂S by
1541 differentiated colonic epithelial cells: implication of the sulfide oxidizing unit
1542 and of the cell respiratory capacity. *Antioxid Redox Signal*, *17*, 1-10.

1543 Min, B., Pelaschier, J. T., Graham, D. E., Tumbula-Hansen, D., & Soll, D. (2002).
1544 Transfer RNA-dependent amino acid biosynthesis: an essential route to
1545 asparagine formation. *Proc Natl Acad Sci U S A*, *99*, 2678-2683.

1546 Minguet, E. G., Vera-Sirera, F., Marina, A., Carbonell, J., & Blazquez, M. A. (2008).
1547 Evolutionary diversification in polyamine biosynthesis. *Mol Biol Evol*, *25*, 2119-
1548 2128.

1549 Molenaar, D., Bosscher, J. S., ten Brink, B., Driessen, A. J., & Konings, W. N. (1993).
1550 Generation of a proton motive force by histidine decarboxylation and
1551 electrogenic histidine/histamine antiport in *Lactobacillus buchneri*. *J Bacteriol*,
1552 *175*, 2864-2870.

1553 Mouille, B., Delpal, S., Mayeur, C., & Blachier, F. (2003). Inhibition of human colon
carcinoma cell growth by ammonia: a non-cytotoxic process associated with
polyamine synthesis reduction. *Biochim Biophys Acta*, *1624*, 88-97.

1556 Mouille, B., Robert, V., & Blachier, F. (2004). Adaptive increase of ornithine
1557 production and decrease of ammonia metabolism in rat colonocytes after
1558 hyperproteic diet ingestion. *Am J Physiol Gastrointest Liver Physiol*, *287*, G344-
1559 351.
1560 Mu, C., Yang, Y., Luo, Z., & Zhu, W. (2015). Metabolomic analysis reveals distinct profiles in the plasma and urine of rats fed a high-protein diet. *Amino Acids*, 47, 1225-1238.

1561 Musch, M. W., Bookstein, C., Xie, Y., Sellin, J. H., & Chang, E. B. (2001). SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells. *Am J Physiol Gastrointest Liver Physiol*, 280, G687-693.

1562 Nakada, Y., & Itoh, Y. (2003). Identification of the putrescine biosynthetic genes in *Pseudomonas aeruginosa* and characterization of agmatine deiminase and N-carbamoylputrescine amidohydrolase of the arginine decarboxylase pathway. *Microbiology*, 149, 707-714.

1563 Neis, E. P., Dejong, C. H., & Rensen, S. S. (2015). The role of microbial amino acid metabolism in host metabolism. *Nutrients*, 7, 2930-2946.

1564 Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., Rochon, J., Gallup, D., Ilkayeva, O., Wenner, B. R., Yancy, W. S., Jr., Eisenson, H., Musante, G., Surwit, R. S., Millington, D. S., Butler, M. D., & Svetkey, L. P. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. *Cell Metab*, 9, 311-326.

1565 Nichols, B. P. (1996). Evolution of genes and enzymes of tryptophan biosynthesis. In F. C. Neidhardt (Ed.), *Escherichia coli and Salmonella: cellular and molecular biology* (Vol. 2, pp. 2638-2648). Washington DC: ASM.

1566 Nolling, J., Breton, G., Omelchenko, M. V., Makarova, K. S., Zeng, Q., Gibson, R., Lee, H. M., Dubois, J., Qiu, D., Hitti, J., Wolf, Y. I., Tatusov, R. L., Sabathe, F., Doucette-Stamm, L., Soucaille, P., Daly, M. J., Bennett, G. N., Koonin, E. V., &
1560 Mu, C., Yang, Y., Luo, Z., & Zhu, W. (2015). Metabolomic analysis reveals distinct profiles in the plasma and urine of rats fed a high-protein diet. *Amino Acids*, 47, 1225-1238.

1563 Musch, M. W., Bookstein, C., Xie, Y., Sellin, J. H., & Chang, E. B. (2001). SCFA increase intestinal Na absorption by induction of NHE3 in rat colon and human intestinal C2/bbe cells. *Am J Physiol Gastrointest Liver Physiol*, 280, G687-693.

1566 Nakada, Y., & Itoh, Y. (2003). Identification of the putrescine biosynthetic genes in *Pseudomonas aeruginosa* and characterization of agmatine deiminase and N-carbamoylputrescine amidohydrolase of the arginine decarboxylase pathway. *Microbiology*, 149, 707-714.

1570 Neis, E. P., Dejong, C. H., & Rensen, S. S. (2015). The role of microbial amino acid metabolism in host metabolism. *Nutrients*, 7, 2930-2946.

1572 Newgard, C. B., An, J., Bain, J. R., Muehlbauer, M. J., Stevens, R. D., Lien, L. F., Haqq, A. M., Shah, S. H., Arlotto, M., Slentz, C. A., Rochon, J., Gallup, D., Ilkayeva, O., Wenner, B. R., Yancy, W. S., Jr., Eisenson, H., Musante, G., Surwit, R. S., Millington, D. S., Butler, M. D., & Svetkey, L. P. (2009). A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. *Cell Metab*, 9, 311-326.

1578 Nichols, B. P. (1996). Evolution of genes and enzymes of tryptophan biosynthesis. In F. C. Neidhardt (Ed.), *Escherichia coli and Salmonella: cellular and molecular biology* (Vol. 2, pp. 2638-2648). Washington DC: ASM.

1581 Nolling, J., Breton, G., Omelchenko, M. V., Makarova, K. S., Zeng, Q., Gibson, R., Lee, H. M., Dubois, J., Qiu, D., Hitti, J., Wolf, Y. I., Tatusov, R. L., Sabathe, F., Doucette-Stamm, L., Soucaille, P., Daly, M. J., Bennett, G. N., Koonin, E. V., &
1584 Smith, D. R. (2001). Genome sequence and comparative analysis of the solvent-producing bacterium *Clostridium acetobutylicum*. *J Bacteriol*, **183**, 4823-4838.

1585 Nyangale, E. P., Mottram, D. S., & Gibson, G. R. (2012). Gut microbial activity, implications for health and disease: the potential role of metabolite analysis. *J Proteome Res*, **11**, 5573-5585.

1589 O'Mahony, S. M., Clarke, G., Borre, Y. E., Dinan, T. G., & Cryan, J. F. (2015).

1590 Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. *Behav Brain Res*, **277**, 32-48.

1592 Oikawa, T. (2007). Alanine, aspartate, and asparagine metabolism in microorganisms.
1593 In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 273-288). Berlin
1594 Heidelberg: Springer-Verlag.

1595 Osborne, D. L., & Seidel, E. R. (1990). Gastrointestinal luminal polyamines: cellular accumulation and enterohepatic circulation. *Am J Physiol*, **258**, G576-584.

1597 Pabst, O., & Bernhardt, G. (2010). The puzzle of intestinal lamina propria dendritic cells and macrophages. *Eur J Immunol*, **40**, 2107-2111.

1599 Panina, E. M., Vitreschak, A. G., Mironov, A. A., & Gelfand, M. S. (2003). Regulation of biosynthesis and transport of aromatic amino acids in low-GC Gram-positive bacteria. *FEMS Microbiol Lett*, **222**, 211-220.

1602 Papillard-Marechal, S., Sznajder, M., Hurtado-Nedelec, M., Alibay, Y., Martin-Schmitt, C., Dehoux, M., Westerman, M., Beaumont, C., Chevallier, B., Puy, H., & Stheneur, C. (2012). Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation. *Am J Clin Nutr*, **95**, 548-554.

1607 Pátek, M. (2007). Branched-Chain Amino Acids. In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 129-162). Berlin Heidelberg: Springer-Verlag.
1584 Smith, D. R. (2001). Genome sequence and comparative analysis of the solvent-producing bacterium *Clostridium acetobutylicum*. *J Bacteriol*, **183**, 4823-4838.

1585 Nyangale, E. P., Mottram, D. S., & Gibson, G. R. (2012). Gut microbial activity, implications for health and disease: the potential role of metabolite analysis. *J Proteome Res*, **11**, 5573-5585.

1589 O'Mahony, S. M., Clarke, G., Borre, Y. E., Dinan, T. G., & Cryan, J. F. (2015).

1590 Serotonin, tryptophan metabolism and the brain-gut-microbiome axis. *Behav Brain Res*, **277**, 32-48.

1592 Oikawa, T. (2007). Alanine, aspartate, and asparagine metabolism in microorganisms.
1593 In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 273-288). Berlin
1594 Heidelberg: Springer-Verlag.

1595 Osborne, D. L., & Seidel, E. R. (1990). Gastrointestinal luminal polyamines: cellular accumulation and enterohepatic circulation. *Am J Physiol*, **258**, G576-584.

1597 Pabst, O., & Bernhardt, G. (2010). The puzzle of intestinal lamina propria dendritic cells and macrophages. *Eur J Immunol*, **40**, 2107-2111.

1599 Panina, E. M., Vitreschak, A. G., Mironov, A. A., & Gelfand, M. S. (2003). Regulation of biosynthesis and transport of aromatic amino acids in low-GC Gram-positive bacteria. *FEMS Microbiol Lett*, **222**, 211-220.

1602 Papillard-Marechal, S., Sznajder, M., Hurtado-Nedelec, M., Alibay, Y., Martin-Schmitt, C., Dehoux, M., Westerman, M., Beaumont, C., Chevallier, B., Puy, H., & Stheneur, C. (2012). Iron metabolism in patients with anorexia nervosa: elevated serum hepcidin concentrations in the absence of inflammation. *Am J Clin Nutr*, **95**, 548-554.

1607 Pátek, M. (2007). Branched-Chain Amino Acids. In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 129-162). Berlin Heidelberg: Springer-Verlag.
1609 Patel, K. P., Luo, F. J., Plummer, N. S., Hostetter, T. H., & Meyer, T. W. (2012). The production of *p*-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. *Clin J Am Soc Nephrol*, 7, 982-988.

1612 Patte, J. C. (1996). Biosynthesis of threonine and lysine. In F. C. Neidhardt (Ed.), *Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology* (Vol. 1, pp. 528–541). Washington, DC: ASM Press.

1615 Pedersen, G., Brynskov, J., & Saermark, T. (2002). Phenol toxicity and conjugation in human colonic epithelial cells. *Scand J Gastroenterol*, 37, 74-79.

1617 Pessione, E. (2012). Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows. *Front Cell Infect Microbiol*, 2, 86.

1619 Pesta, D. H., & Samuel, V. T. (2014). A high-protein diet for reducing body fat: mechanisms and possible caveats. *Nutr Metab (Lond)*, 11, 53.

1621 Peters-Wendisch, P., Stolz, M., Etterich, H., Kennerknecht, N., Sahm, H., & Eggeling, L. (2005). Metabolic engineering of *Corynebacterium glutamicum* for L-serine production. *Appl Environ Microbiol*, 71, 7139-7144.

1624 Pitcher, M. C., & Cummings, J. H. (1996). Hydrogen sulphide: a bacterial toxin in ulcerative colitis? *Gut*, 39, 1-4.

1626 Pittard, J. (1996). Biosynthesis of the aromatic amino acids. In F. C. Neidhardt (Ed.), *Escherichia coli and Salmonella: cellular and molecular biology* (Vol. 1, pp. 458-484). Washington DC: ASM.

1629 Poesen, R., Mutsaers, H. A., Windey, K., van den Broek, P. H., Verweij, V., Augustijns, P., Kuypers, D., Jansen, J., Evenepoel, P., Verbeke, K., Meijers, B., & Masereeuw, R. (2015). The influence of dietary protein intake on mammalian tryptophan and phenolic metabolites. *PLoS One*, 10, e0140820.
1609 Patel, K. P., Luo, F. J., Plummer, N. S., Hostetter, T. H., & Meyer, T. W. (2012). The production of *p*-cresol sulfate and indoxyl sulfate in vegetarians versus omnivores. *Clin J Am Soc Nephrol*, 7, 982-988.

1612 Patte, J. C. (1996). Biosynthesis of threonine and lysine. In F. C. Neidhardt (Ed.), *Escherichia coli and Salmonella typhimurium: Cellular and Molecular Biology* (Vol. 1, pp. 528–541). Washington, DC: ASM Press.

1615 Pedersen, G., Brynskov, J., & Saermark, T. (2002). Phenol toxicity and conjugation in human colonic epithelial cells. *Scand J Gastroenterol*, 37, 74-79.

1617 Pessione, E. (2012). Lactic acid bacteria contribution to gut microbiota complexity: lights and shadows. *Front Cell Infect Microbiol*, 2, 86.

1619 Pesta, D. H., & Samuel, V. T. (2014). A high-protein diet for reducing body fat: mechanisms and possible caveats. *Nutr Metab (Lond)*, 11, 53.

1621 Peters-Wendisch, P., Stolz, M., Etterich, H., Kennerknecht, N., Sahm, H., & Eggeling, L. (2005). Metabolic engineering of *Corynebacterium glutamicum* for L-serine production. *Appl Environ Microbiol*, 71, 7139-7144.

1624 Pitcher, M. C., & Cummings, J. H. (1996). Hydrogen sulphide: a bacterial toxin in ulcerative colitis? *Gut*, 39, 1-4.

1626 Pittard, J. (1996). Biosynthesis of the aromatic amino acids. In F. C. Neidhardt (Ed.), *Escherichia coli and Salmonella: cellular and molecular biology* (Vol. 1, pp. 458-484). Washington DC: ASM.

1629 Poesen, R., Mutsaers, H. A., Windey, K., van den Broek, P. H., Verweij, V., Augustijns, P., Kuypers, D., Jansen, J., Evenepoel, P., Verbeke, K., Meijers, B., & Masereeuw, R. (2015). The influence of dietary protein intake on mammalian tryptophan and phenolic metabolites. *PLoS One*, 10, e0140820.
1633 Polo, L. M., Gil-Ortiz, F., Cantin, A., & Rubio, V. (2012). New insight into the
1634 transcarbamylase family: the structure of putrescine transcarbamylase, a key
1635 catalyst for fermentative utilization of agmatine. *PLoS One*, 7, e31528.

1636 Pridmore, R. D., Berger, B., Desiere, F., Vilanova, D., Barretto, C., Pittet, A. C.,
1637 Zwahlen, M. C., Rouvet, M., Altermann, E., Barrangou, R., Mollet, B.,
1638 Mercenier, A., Klaenhammer, T., Arigoni, F., & Schell, M. A. (2004). The
1639 genome sequence of the probiotic intestinal bacterium *Lactobacillus johnsonii*
1640 NCC 533. *Proc Natl Acad Sci U S A*, 101, 2512-2517.

1641 Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T.,
1642 Pons, N., Levenez, F., Yamada, T., Mende, D. R., Li, J., Xu, J., Li, S., Li, D.,
1643 Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan,
1644 M., Batto, J. M., Hansen, T., Le Paslier, D., Linneberg, A., Nielsen, H. B.,
1645 Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li,
1646 S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J.,
1647 Brunak, S., Dore, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J.,
1648 Weissenbach, J., Meta, H. I. T. C., Bork, P., Ehrlich, S. D., & Wang, J. (2010).
1649 A human gut microbial gene catalogue established by metagenomic sequencing.
1650 *Nature*, 464, 59-65.

1651 Ramakrishna, B. S., Roberts-Thomson, I. C., Pannall, P. R., & Roediger, W. E. (1991).
1652 Impaired sulphation of phenol by the colonic mucosa in quiescent and active
1653 ulcerative colitis. *Gut*, 32, 46-49.

1654 Rampelli, S., Candela, M., Turroni, S., Biagi, E., Collino, S., Franceschi, C., O'Toole, P.
1655 W., & Brigidi, P. (2013). Functional metagenomic profiling of intestinal
1656 microbiome in extreme ageing. *Aging (Albany NY)*, 5, 902-912.
1633 Polo, L. M., Gil-Ortiz, F., Cantin, A., & Rubio, V. (2012). New insight into the
1634 transcarbamylase family: the structure of putrescine transcarbamylase, a key
1635 catalyst for fermentative utilization of agmatine. *PLoS One*, 7, e31528.

1636 Pridmore, R. D., Berger, B., Desiere, F., Vilanova, D., Barretto, C., Pittet, A. C.,
1637 Zwahlen, M. C., Rouvet, M., Altermann, E., Barrangou, R., Mollet, B.,
1638 Mercenier, A., Klaenhammer, T., Arigoni, F., & Schell, M. A. (2004). The
1639 genome sequence of the probiotic intestinal bacterium *Lactobacillus johnsonii*
1640 NCC 533. *Proc Natl Acad Sci U S A*, 101, 2512-2517.

1641 Qin, J., Li, R., Raes, J., Arumugam, M., Burgdorf, K. S., Manichanh, C., Nielsen, T.,
1642 Pons, N., Levenez, F., Yamada, T., Mende, D. R., Li, J., Xu, J., Li, S., Li, D.,
1643 Cao, J., Wang, B., Liang, H., Zheng, H., Xie, Y., Tap, J., Lepage, P., Bertalan,
1644 M., Batto, J. M., Hansen, T., Le Paslier, D., Linneberg, A., Nielsen, H. B.,
1645 Pelletier, E., Renault, P., Sicheritz-Ponten, T., Turner, K., Zhu, H., Yu, C., Li,
1646 S., Jian, M., Zhou, Y., Li, Y., Zhang, X., Li, S., Qin, N., Yang, H., Wang, J.,
1647 Brunak, S., Dore, J., Guarner, F., Kristiansen, K., Pedersen, O., Parkhill, J.,
1648 Weissenbach, J., Meta, H. I. T. C., Bork, P., Ehrlich, S. D., & Wang, J. (2010).
1649 A human gut microbial gene catalogue established by metagenomic sequencing.
1650 *Nature*, 464, 59-65.

1651 Ramakrishna, B. S., Roberts-Thomson, I. C., Pannall, P. R., & Roediger, W. E. (1991).
1652 Impaired sulphation of phenol by the colonic mucosa in quiescent and active
1653 ulcerative colitis. *Gut*, 32, 46-49.

1654 Rampelli, S., Candela, M., Turroni, S., Biagi, E., Collino, S., Franceschi, C., O'Toole, P.
1655 W., & Brigidi, P. (2013). Functional metagenomic profiling of intestinal
1656 microbiome in extreme ageing. *Aging (Albany NY)*, 5, 902-912.
1657 Rand, W. M., Pellett, P. L., & Young, V. R. (2003). Meta-analysis of nitrogen balance
1658 studies for estimating protein requirements in healthy adults. *Am J Clin Nutr*, 77,
1659 109-127.

1660 Rawlings, N. D., Waller, M., Barrett, A. J., & Bateman, A. (2014). MEROPS: the
1661 database of proteolytic enzymes, their substrates and inhibitors. *Nucleic Acids
1662 Res*, 42, D503-509.

1663 Rechkemmer, G., Ronnau, K., & von Engelhardt, W. (1988). Fermentation of
1664 polysaccharides and absorption of short chain fatty acids in the mammalian
1665 hindgut. *Comp Biochem Physiol A Comp Physiol*, 90, 563-568.

1666 Reiffenstein, R. J., Hulbert, W. C., & Roth, S. H. (1992). Toxicology of hydrogen
1667 sulfide. *Annu Rev Pharmacol Toxicol*, 32, 109-134.

1668 Reigstad, C. S., Salmonson, C. E., Rainey, J. F., 3rd, Szurszewski, J. H., Linden, D. R.,
1669 Sonnenburg, J. L., Farrugia, G., & Kashyap, P. C. (2015). Gut microbes promote
1670 colonic serotonin production through an effect of short-chain fatty acids on
1671 enterochromaffin cells. *FASEB J*, 29, 1395-1403.

1672 Reitzer, L. J., & Magasanik, B. (1987). Ammonium assimilation and the biosynthesis of
1673 glutamine, glutamate, aspartate, asparagine, L-alanine, and D-alanine. In J. L. I.
1674 F.C.Neidhardt, K. B. Low, B. Magasanik, M. Schaechter, and H. E. Umbarger
1675 (Ed.), *Escherichia coli and Salmonella typhimurium: cellular and molecular
1676 biology* (pp. 302-320). Washington, D.C.: American Society for Microbiology.

1677 Remesy, C., Fafournoux, P., & Demigne, C. (1983). Control of hepatic utilization of
1678 serine, glycine and threonine in fed and starved rats. *J Nutr*, 113, 28-39.

1679 Rodionov, D. A., Vitreschak, A. G., Mironov, A. A., & Gelfand, M. S. (2004).
1680 Comparative genomics of the methionine metabolism in Gram-positive bacteria:
1681 a variety of regulatory systems. *Nucleic Acids Res*, 32, 3340-3353.
1657 Rand, W. M., Pellett, P. L., & Young, V. R. (2003). Meta-analysis of nitrogen balance studies for estimating protein requirements in healthy adults. *Am J Clin Nutr*, 77, 109-127.

1660 Rawlings, N. D., Waller, M., Barrett, A. J., & Bateman, A. (2014). MEROPS: the database of proteolytic enzymes, their substrates and inhibitors. *Nucleic Acids Res*, 42, D503-509.

1663 Rechkemmer, G., Ronnau, K., & von Engelhardt, W. (1988). Fermentation of polysaccharides and absorption of short chain fatty acids in the mammalian hindgut. *Comp Biochem Physiol A Comp Physiol*, 90, 563-568.

1666 Reiffenstein, R. J., Hulbert, W. C., & Roth, S. H. (1992). Toxicology of hydrogen sulfide. *Annu Rev Pharmacol Toxicol*, 32, 109-134.

1668 Reigstad, C. S., Salmonson, C. E., Rainey, J. F., 3rd, Szurszewski, J. H., Linden, D. R., Sonnenburg, J. L., Farrugia, G., & Kashyap, P. C. (2015). Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. *FASEB J*, 29, 1395-1403.

1672 Reitzer, L. J., & Magasanik, B. (1987). Ammonium assimilation and the biosynthesis of glutamine, glutamate, aspartate, asparagine, L-alanine, and D-alanine. In J. L. I. F.C.Neidhardt, K. B. Low, B. Magasanik, M. Schaechter, and H. E. Umbarger (Ed.), *Escherichia coli and Salmonella typhimurium: cellular and molecular biology* (pp. 302-320). Washington, D.C.: American Society for Microbiology.

1677 Remesy, C., Fafournoux, P., & Demigne, C. (1983). Control of hepatic utilization of serine, glycine and threonine in fed and starved rats. *J Nutr*, 113, 28-39.

1679 Rodionov, D. A., Vitreschak, A. G., Mironov, A. A., & Gelfand, M. S. (2004). Comparative genomics of the methionine metabolism in Gram-positive bacteria: a variety of regulatory systems. *Nucleic Acids Res*, 32, 3340-3353.
1682 Rossi, M., Johnson, D. W., Morrison, M., Pascoe, E., Coombes, J. S., Forbes, J. M., McWhinney, B. C., Ungerer, J. P., Dimeski, G., & Campbell, K. L. (2014).
1683 SYNbiotics Easing Renal failure by improving Gut microbiology (SYNERGY): a protocol of placebo-controlled randomised cross-over trial. *BMC Nephrol*, 15, 106.

1687 Russell, W. R., Gratz, S. W., Duncan, S. H., Holtrop, G., Ince, J., Scobbie, L., Duncan, G., Johnstone, A. M., Lobley, G. E., Wallace, R. J., Duthie, G. G., & Flint, H. J. (2011). High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. *Am J Clin Nutr*, 93, 1062-1072.

1692 Saier, M. H., Jr. (2000). Families of transmembrane transporters selective for amino acids and their derivatives. *Microbiology*, 146 ( Pt 8 ), 1775-1795.

1694 Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M., & Gordon, J. I. (2008). Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. *Proc Natl Acad Sci U S A*, 105, 16767-16772.

1699 Sanders, J. W., Leenhouts, K., Burghoorn, J., Brands, J. R., Venema, G., & Kok, J. (1998). A chloride-inducible acid resistance mechanism in *Lactococcus lactis* and its regulation. *Mol Microbiol*, 27, 299-310.

1702 Santesso, N., Akl, E. A., Bianchi, M., Mente, A., Mustafa, R., Heels-Ansdell, D., & Schunemann, H. J. (2012). Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis. *Eur J Clin Nutr*, 66, 780-788.
1682 Rossi, M., Johnson, D. W., Morrison, M., Pascoe, E., Coombes, J. S., Forbes, J. M., McWhinney, B. C., Ungerer, J. P., Dimeski, G., & Campbell, K. L. (2014).
1683 SYNbiotics Easing Renal failure by improving Gut microbiology (SYNERGY): a protocol of placebo-controlled randomised cross-over trial. BMC Nephrol, 15, 106.
1684
1685
1686
1687 Russell, W. R., Gratz, S. W., Duncan, S. H., Holtrop, G., Ince, J., Scobbie, L., Duncan, G., Johnstone, A. M., Lobley, G. E., Wallace, R. J., Duthie, G. G., & Flint, H. J. (2011). High-protein, reduced-carbohydrate weight-loss diets promote metabolite profiles likely to be detrimental to colonic health. Am J Clin Nutr, 93, 1062-1072.
1689
1690
1691
1692 Saier, M. H., Jr. (2000). Families of transmembrane transporters selective for amino acids and their derivatives. Microbiology, 146 (Pt 8), 1775-1795.
1693
1694 Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M., & Gordon, J. I.
1695
1696
1697
1698
(2008). Effects of the gut microbiota on host adiposity are modulated by the short-chain fatty-acid binding G protein-coupled receptor, Gpr41. Proc Natl Acad Sci U S A, 105, 16767-16772.
1699
1700
1701
Sanders, J. W., Leenhouts, K., Burghoorn, J., Brands, J. R., Venema, G., & Kok, J. (1998). A chloride-inducible acid resistance mechanism in Lactococcus lactis and its regulation. Mol Microbiol, 27, 299-310.
1702
1703
1704
1705
Santesso, N., Akl, E. A., Bianchi, M., Mente, A., Mustafa, R., Heels-Ansdell, D., & Schunemann, H. J. (2012). Effects of higher- versus lower-protein diets on health outcomes: a systematic review and meta-analysis. Eur J Clin Nutr, 66, 780-788.
1706 Schell, M. A., Karmirantzou, M., Snel, B., Vilanova, D., Berger, B., Pessi, G., Zwahlen, M. C., Desiere, F., Bork, P., Delley, M., Pridmore, R. D., & Arigoni, F. (2002).
1707 The genome sequence of *Bifidobacterium longum* reflects its adaptation to the human gastrointestinal tract. *Proc Natl Acad Sci U S A*, 99, 14422-14427.
1708
1709 Selmer, T., & Andrei, P. I. (2001). *p*-Hydroxyphenylacetate decarboxylase from *Clostridium difficile*. A novel glycyl radical enzyme catalysing the formation of *p*-cresol. *Eur J Biochem*, 268, 1363-1372.
1710
1711
1712 Shimizu, H., & Hirasawa, T. (2007). Production of glutamate and glutamate-related amino acids: molecular mechanism analysis and metabolic engineering. In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 1-38). Berlin Heidelberg: Springer-Verlag.
1713
1714
1715
1716 Shimizu, T., Ohtani, K., Hirakawa, H., Ohshima, K., Yamashita, A., Shiba, T., Ogasawara, N., Hattori, M., Kuhara, S., & Hayashi, H. (2002). Complete genome sequence of *Clostridium perfringens*, an anaerobic flesh-eater. *Proc Natl Acad Sci U S A*, 99, 996-1001.
1717
1718
1719
1720 Shoda, R., Matsueda, K., Yamato, S., & Umeda, N. (1996). Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. *Am J Clin Nutr*, 63, 741-745.
1721
1722
1723
1724 Smith, E. A., & Macfarlane, G. T. (1996). Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism. *J Appl Bacteriol*, 81, 288-302.
1725
1726
1727
1728
1706 Schell, M. A., Karmirantzou, M., Snel, B., Vilanova, D., Berger, B., Pessi, G., Zwahlen, M. C., Desiere, F., Bork, P., Delley, M., Pridmore, R. D., & Arigoni, F. (2002).
1707 The genome sequence of *Bifidobacterium longum* reflects its adaptation to the human gastrointestinal tract. *Proc Natl Acad Sci U S A*, 99, 14422-14427.
1708
1709 Selmer, T., & Andrei, P. I. (2001). *p*-Hydroxyphenylacetate decarboxylase from *Clostridium difficile*. A novel glycyl radical enzyme catalysing the formation of *p*-cresol. *Eur J Biochem*, 268, 1363-1372.
1710
1711
1712 Shimizu, H., & Hirasawa, T. (2007). Production of glutamate and glutamate-related amino acids: molecular mechanism analysis and metabolic engineering. In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 1-38). Berlin Heidelberg: Springer-Verlag.
1713
1714
1715
1716 Shimizu, T., Ohtani, K., Hirakawa, H., Ohshima, K., Yamashita, A., Shiba, T., Ogasawara, N., Hattori, M., Kuhara, S., & Hayashi, H. (2002). Complete genome sequence of *Clostridium perfringens*, an anaerobic flesh-eater. *Proc Natl Acad Sci U S A*, 99, 996-1001.
1717
1718
1719
1720 Shoda, R., Matsueda, K., Yamato, S., & Umeda, N. (1996). Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. *Am J Clin Nutr*, 63, 741-745.
1721
1722
1723
1724 Smith, E. A., & Macfarlane, G. T. (1996). Enumeration of human colonic bacteria producing phenolic and indolic compounds: effects of pH, carbohydrate availability and retention time on dissimilatory aromatic amino acid metabolism. *J Appl Bacteriol*, 81, 288-302.
1725
1726
1727
1728
1729 Smith, E. A., & Macfarlane, G. T. (1997). Formation of phenolic and indolic compounds by anaerobic bacteria in the human large intestine. *Microb Ecol, 33*, 180-188.

1732 Sprenger, G. A. (2007). Aromatic amino acids. In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 93-127). Berlin Heidelberg: Springer-Verlag.

1734 Sridharan, G. V., Choi, K., Klemashevich, C., Wu, C., Prabakaran, D., Pan, L. B., Steinmeyer, S., Mueller, C., Yousofshahi, M., Alaniz, R. C., Lee, K., & Jayaraman, A. (2014). Prediction and quantification of bioactive microbiota metabolites in the mouse gut. *Nat Commun, 5*, 5492.

1738 Steiner, H. Y., Naider, F., & Becker, J. M. (1995). The PTR family: a new group of peptide transporters. *Mol Microbiol, 16*, 825-834.

1740 Steinert, R. E., Beglinger, C., & Langhans, W. (2015). Intestinal GLP-1 and satiation: from man to rodents and back. *Int J Obes (Lond)*.

1742 Stolz, M., Peters-Wendisch, P., Etterich, H., Gerharz, T., Faurie, R., Sahm, H., Fersterra, H., & Eggeling, L. (2007). Reduced folate supply as a key to enhanced L-serine production by *Corynebacterium glutamicum*. *Appl Environ Microbiol*, 73, 750-755.

1746 Sudhamsu, J., & Crane, B. R. (2009). Bacterial nitric oxide synthases: what are they good for? *Trends Microbiol, 17*, 212-218.

1748 Szabo, C., Coletta, C., Chao, C., Modis, K., Szczesny, B., Papapetropoulos, A., & Hellmich, M. R. (2013). Tumor-derived hydrogen sulfide, produced by cystathionine-beta-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer. *Proc Natl Acad Sci U S A*, 110, 12474-12479.

1752 Tabor, C. W., & Tabor, H. (1985). Polyamines in microorganisms. *Microbiol Rev*, 49, 81-99.
1729 Smith, E. A., & Macfarlane, G. T. (1997). Formation of phenolic and indolic compounds by anaerobic bacteria in the human large intestine. *Microb Ecol, 33*, 180-188.

1732 Sprenger, G. A. (2007). Aromatic amino acids. In V. F. Wendisch (Ed.), *Amino Acid Biosynthesis* (pp. 93-127). Berlin Heidelberg: Springer-Verlag.

1734 Sridharan, G. V., Choi, K., Klemashevich, C., Wu, C., Prabakaran, D., Pan, L. B., Steinmeyer, S., Mueller, C., Yousofshahi, M., Alaniz, R. C., Lee, K., & Jayaraman, A. (2014). Prediction and quantification of bioactive microbiota metabolites in the mouse gut. *Nat Commun, 5*, 5492.

1738 Steiner, H. Y., Naider, F., & Becker, J. M. (1995). The PTR family: a new group of peptide transporters. *Mol Microbiol, 16*, 825-834.

1740 Steinert, R. E., Beglinger, C., & Langhans, W. (2015). Intestinal GLP-1 and satiation: from man to rodents and back. *Int J Obes (Lond).*

1742 Stolz, M., Peters-Wendisch, P., Etterich, H., Gerharz, T., Faurie, R., Sahm, H., Fersterra, H., & Eggeling, L. (2007). Reduced folate supply as a key to enhanced L-serine production by *Corynebacterium glutamicum*. *Appl Environ Microbiol*, 73, 750-755.

1746 Sudhamsu, J., & Crane, B. R. (2009). Bacterial nitric oxide synthases: what are they good for? *Trends Microbiol, 17*, 212-218.

1748 Szabo, C., Coletta, C., Chao, C., Modis, K., Szczesny, B., Papapetropoulos, A., & Hellmich, M. R. (2013). Tumor-derived hydrogen sulfide, produced by cystathionine-beta-synthase, stimulates bioenergetics, cell proliferation, and angiogenesis in colon cancer. *Proc Natl Acad Sci U S A, 110*, 12474-12479.

1752 Tabor, C. W., & Tabor, H. (1985). Polyamines in microorganisms. *Microbiol Rev, 49*, 81-99.
1754 Thomas, C. M., Hong, T., van Pijkeren, J. P., Hemarajata, P., Trinh, D. V., Hu, W.,
1755 Britton, R. A., Kalkum, M., & Versalovic, J. (2012). Histamine derived from
1756 probiotic *Lactobacillus reuteri* suppresses TNF via modulation of PKA and
1757 ERK signaling. *PLoS One*, 7, e31951.

1758 Toden, S., Belobrajdic, D. P., Bird, A. R., Topping, D. L., & Conlon, M. A. (2010).
1759 Effects of dietary beef and chicken with and without high amylose maize starch
1760 on blood malondialdehyde, interleukins, IGF-I, insulin, leptin, MMP-2, and
1761 TIMP-2 concentrations in rats. *Nutr Cancer*, 62, 454-465.

1762 Toden, S., Bird, A. R., Topping, D. L., & Conlon, M. A. (2005). Resistant starch
1763 attenuates colonic DNA damage induced by higher dietary protein in rats. *Nutr
1764 Cancer*, 51, 45-51.

1765 Tremaroli, V., & Backhed, F. (2012). Functional interactions between the gut
1766 microbiota and host metabolism. *Nature*, 489, 242-249.

1767 Trivedi, V., Gupta, A., Jala, V. R., Saravanan, P., Rao, G. S., Rao, N. A., Savithri, H. S.,
1768 & Subramanya, H. S. (2002). Crystal structure of binary and ternary complexes
1769 of serine hydroxymethyltransferase from *Bacillus stearothermophilus*: insights
1770 into the catalytic mechanism. *J Biol Chem*, 277, 17161-17169.

1771 Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E.,
1772 Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., Egholm, M., Henrissat,
1773 B., Heath, A. C., Knight, R., & Gordon, J. I. (2009). A core gut microbiome in
1774 obese and lean twins. *Nature*, 457, 480-484.

1775 Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon,
1776 J. I. (2006). An obesity-associated gut microbiome with increased capacity for
1777 energy harvest. *Nature*, 444, 1027-1031.
1754 Thomas, C. M., Hong, T., van Pijkeren, J. P., Hemarajata, P., Trinh, D. V., Hu, W.,
1755 Britton, R. A., Kalkum, M., & Versalovic, J. (2012). Histamine derived from
1756 probiotic *Lactobacillus reuteri* suppresses TNF via modulation of PKA and
1757 ERK signaling. *PLoS One*, 7, e31951.

1758 Toden, S., Belobrajdic, D. P., Bird, A. R., Topping, D. L., & Conlon, M. A. (2010).
1759 Effects of dietary beef and chicken with and without high amylose maize starch
1760 on blood malondialdehyde, interleukins, IGF-I, insulin, leptin, MMP-2, and
1761 TIMP-2 concentrations in rats. *Nutr Cancer*, 62, 454-465.

1762 Toden, S., Bird, A. R., Topping, D. L., & Conlon, M. A. (2005). Resistant starch
1763 attenuates colonic DNA damage induced by higher dietary protein in rats. *Nutr
1764 Cancer*, 51, 45-51.

1765 Tremaroli, V., & Backhed, F. (2012). Functional interactions between the gut
1766 microbiota and host metabolism. *Nature*, 489, 242-249.

1767 Trivedi, V., Gupta, A., Jala, V. R., Saravanan, P., Rao, G. S., Rao, N. A., Savithri, H. S.,
1768 & Subramanya, H. S. (2002). Crystal structure of binary and ternary complexes
1769 of serine hydroxymethyltransferase from *Bacillus stearothermophilus*: insights
1770 into the catalytic mechanism. *J Biol Chem*, 277, 17161-17169.

1771 Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E.,
1772 Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., Egholm, M., Henrissat,
1773 B., Heath, A. C., Knight, R., & Gordon, J. I. (2009). A core gut microbiome in
1774 obese and lean twins. *Nature*, 457, 480-484.

1775 Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon,
1776 J. I. (2006). An obesity-associated gut microbiome with increased capacity for
1777 energy harvest. *Nature*, 444, 1027-1031.
1778 Umbarger, H. E. (1978). Amino acid biosynthesis and its regulation. *Annu Rev*

1779 *Biochem*, **47**, 532-606.

1780 Umbarger, H. E. (1996). Biosynthesis of the branched-chain amino acids. In F. C.

1781 Neidhardt, J. L. Ingraham, B. L. Low, B. Magasanik, M. Schaechter & H. E.

1782 Umbarger (Eds.), *Escherichia coli and Salmonella typhimurium* (pp. 442–457).

1783 Washington, DC: ASM Press.

1784 Vanholder, R., & Glorieux, G. (2015). The intestine and the kidneys: a bad marriage

1785 can be hazardous. *Clin Kidney J*, **8**, 168-179.

1786 Vanholder, R., Schepers, E., Pletinck, A., Nagler, E. V., & Glorieux, G. (2014). The

1787 uremic toxicity of indoxyl sulfate and *p*-cresyl sulfate: a systematic review. *J Am*

1788 *Soc Nephrol*, **25**, 1897-1907.

1789 Vaziri, N. D., Liu, S. M., Lau, W. L., Khazaeli, M., Nazertehrani, S., Farzaneh, S. H.,

1790 Kieffer, D. A., Adams, S. H., & Martin, R. J. (2014). High amylose resistant

1791 starch diet ameliorates oxidative stress, inflammation, and progression of

1792 chronic kidney disease. *PLoS One*, **9**, e114881.

1793 Vaziri, N. D., Wong, J., Pahl, M., Piceno, Y. M., Yuan, J., DeSantis, T. Z., Ni, Z.,

1794 Nguyen, T. H., & Andersen, G. L. (2013). Chronic kidney disease alters

1795 intestinal microbial flora. *Kidney Int*, **83**, 308-315.

1796 Vaziri, N. D., Yuan, J., & Norris, K. (2013). Role of urea in intestinal barrier

1797 dysfunction and disruption of epithelial tight junction in chronic kidney disease.

1798 *Am J Nephrol*, **37**, 1-6.

1799 Venkatesh, M., Mukherjee, S., Wang, H., Li, H., Sun, K., Benechet, A. P., Qiu, Z.,

1800 Maher, L., Redinbo, M. R., Phillips, R. S., Fleet, J. C., Kortagere, S., Mukherjee,

1801 P., Fasano, A., Le Ven, J., Nicholson, J. K., Dumas, M. E., Khanna, K. M., &

1802 Mani, S. (2014). Symbiotic bacterial metabolites regulate gastrointestinal barrier
1778 Umbarger, H. E. (1978). Amino acid biosynthesis and its regulation. *Annu Rev*

1779 *Biochem*, **47**, 532-606.

1780 Umbarger, H. E. (1996). Biosynthesis of the branched-chain amino acids. In F. C.

1781 Neidhardt, J. L. Ingraham, B. L. Low, B. Magasanik, M. Schaechter & H. E.

1782 Umbarger (Eds.), *Escherichia coli and Salmonella typhimurium* (pp. 442–457).

1783 Washington, DC: ASM Press.

1784 Vanholder, R., & Glorieux, G. (2015). The intestine and the kidneys: a bad marriage

1785 can be hazardous. *Clin Kidney J*, **8**, 168-179.

1786 Vanholder, R., Schepers, E., Pletinck, A., Nagler, E. V., & Glorieux, G. (2014). The

1787 uremic toxicity of indoxyl sulfate and *p*-cresyl sulfate: a systematic review. *J Am*

1788 *Soc Nephrol*, **25**, 1897-1907.

1789 Vaziri, N. D., Liu, S. M., Lau, W. L., Khazaeli, M., Nazertehrani, S., Farzaneh, S. H.,

1790 Kieffer, D. A., Adams, S. H., & Martin, R. J. (2014). High amylose resistant

1791 starch diet ameliorates oxidative stress, inflammation, and progression of

1792 chronic kidney disease. *PLoS One*, **9**, e114881.

1793 Vaziri, N. D., Wong, J., Pahl, M., Piceno, Y. M., Yuan, J., DeSantis, T. Z., Ni, Z.,

1794 Nguyen, T. H., & Andersen, G. L. (2013). Chronic kidney disease alters

1795 intestinal microbial flora. *Kidney Int*, **83**, 308-315.

1796 Vaziri, N. D., Yuan, J., & Norris, K. (2013). Role of urea in intestinal barrier

1797 dysfunction and disruption of epithelial tight junction in chronic kidney disease.

1798 *Am J Nephrol*, **37**, 1-6.

1799 Venkatesh, M., Mukherjee, S., Wang, H., Li, H., Sun, K., Benechet, A. P., Qiu, Z.,

1800 Maher, L., Redinbo, M. R., Phillips, R. S., Fleet, J. C., Kortagere, S., Mukherjee,

1801 P., Fasano, A., Le Ven, J., Nicholson, J. K., Dumas, M. E., Khanna, K. M., &

1802 Mani, S. (2014). Symbiotic bacterial metabolites regulate gastrointestinal barrier
1803 function via the xenobiotic sensor PXR and Toll-like receptor 4. *Immunity*, 41,
1804 296-310.

1805 Vitreschak, A. G., Lyubetskaya, E. V., Shirshin, M. A., Gelfand, M. S., & Lyubetsky, V. A. (2004). Attenuation regulation of amino acid biosynthetic operons in proteobacteria: comparative genomics analysis. *FEMS Microbiol Lett*, 234, 357-370.

1809 Wall, R., Ross, R. P., & Stanton, C. (2014). Bacterial neuroactive compounds produced by psychobiotics. In M. Lyte & J. F. Cryan (Eds.), *Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease* (Vol. 817). New York: Springer.

1813 Wang, T. J., Larson, M. G., Vasan, R. S., Cheng, S., Rhee, E. P., McCabe, E., Lewis, G. D., Fox, C. S., Jacques, P. F., Fernandez, C., O'Donnell, C. J., Carr, S. A., Mootha, V. K., Florez, J. C., Souza, A., Melander, O., Clish, C. B., & Gerszten, R. E. (2011). Metabolite profiles and the risk of developing diabetes. *Nat Med*, 17, 448-453.

1818 Watanabe, H., Miyamoto, Y., Honda, D., Tanaka, H., Wu, Q., Endo, M., Noguchi, T., Kadowaki, D., Ishima, Y., Kotani, S., Nakajima, M., Kataoka, K., Kim-Mitsuyama, S., Tanaka, M., Fukagawa, M., Otagiri, M., & Maruyama, T. (2013). *p*-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. *Kidney Int*, 83, 582-592.

1823 Westerterp-Plantenga, M. S., Nieuwenhuizen, A., Tome, D., Soenen, S., & Westerterp, K. R. (2009). Dietary protein, weight loss, and weight maintenance. *Annu Rev Nutr*, 29, 21-41.
1803 function via the xenobiotic sensor PXR and Toll-like receptor 4. *Immunity*, 41,
1804 296-310.

1805 Vitreschak, A. G., Lyubetskaya, E. V., Shirshin, M. A., Gelfand, M. S., & Lyubetsky, V. A. (2004). Attenuation regulation of amino acid biosynthetic operons in proteobacteria: comparative genomics analysis. *FEMS Microbiol Lett*, 234, 357-370.

1809 Wall, R., Ross, R. P., & Stanton, C. (2014). Bacterial neuroactive compounds produced by psychobiotics. In M. Lyte & J. F. Cryan (Eds.), *Microbial Endocrinology: The Microbiota-Gut-Brain Axis in Health and Disease* (Vol. 817). New York: Springer.

1813 Wang, T. J., Larson, M. G., Vasan, R. S., Cheng, S., Rhee, E. P., McCabe, E., Lewis, G. D., Fox, C. S., Jacques, P. F., Fernandez, C., O'Donnell, C. J., Carr, S. A., Mootha, V. K., Florez, J. C., Souza, A., Melander, O., Clish, C. B., & Gerszten, R. E. (2011). Metabolite profiles and the risk of developing diabetes. *Nat Med*, 17, 448-453.

1818 Watanabe, H., Miyamoto, Y., Honda, D., Tanaka, H., Wu, Q., Endo, M., Noguchi, T., Kadowaki, D., Ishima, Y., Kotani, S., Nakajima, M., Kataoka, K., Kim-Mitsuyama, S., Tanaka, M., Fukagawa, M., Otagiri, M., & Maruyama, T. (2013). *p*-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. *Kidney Int*, 83, 582-592.

1823 Westerterp-Plantenga, M. S., Nieuwenhuizen, A., Tome, D., Soenen, S., & Westerterp, K. R. (2009). Dietary protein, weight loss, and weight maintenance. *Annu Rev Nutr*, 29, 21-41.
1826 Widner, B., Leblhuber, F., Walli, J., Tilz, G. P., Demel, U., & Fuchs, D. (1999).

1827 Degradation of tryptophan in neurodegenerative disorders. *Adv Exp Med Biol,* 467, 133-138.

1828

1829 Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., &

1830 Siuzdak, G. (2009). Metabolomics analysis reveals large effects of gut

1831 microflora on mammalian blood metabolites. *Proc Natl Acad Sci U S A,* 106,

1832 3698-3703.

1833 Williams, B. B., Van Benschoten, A. H., Cimermancic, P., Donia, M. S., Zimmermann,

1834 M., Taketani, M., Ishihara, A., Kashyap, P. C., Fraser, J. S., & Fischbach, M. A.

1835 (2014). Discovery and characterization of gut microbiota decarboxylases that

1836 can produce the neurotransmitter tryptamine. *Cell Host Microbe,* 16, 495-503.

1837 Windey, K., De Preter, V., Louat, T., Schuit, F., Herman, J., Vansant, G., & Verbeke,

1838 K. (2012). Modulation of protein fermentation does not affect fecal water

1839 toxicity: a randomized cross-over study in healthy subjects. *PLoS One,* 7,

1840 e52387.

1841 Wong, J., Piceno, Y. M., Desantis, T. Z., Pahl, M., Andersen, G. L., & Vaziri, N. D.

1842 (2014). Expansion of urease- and uricase-containing, indole- and p-cresol-

1843 forming and contraction of short-chain fatty acid-producing intestinal microbiota

1844 in ESRD. *Am J Nephrol,* 39, 230-237.

1845 Wu, G., Fanzo, J., Miller, D. D., Pingali, P., Post, M., Steiner, J. L., & Thalacker-

1846 Mercer, A. E. (2014). Production and supply of high-quality food protein for

1847 human consumption: sustainability, challenges, and innovations. *Ann N Y Acad

1848 *Sci,* 1321, 1-19.
1826 Widner, B., Leblhuber, F., Walli, J., Tilz, G. P., Demel, U., & Fuchs, D. (1999).

1827 Degradation of tryptophan in neurodegenerative disorders. *Adv Exp Med Biol,* 467, 133-138.

1828

1829 Wikoff, W. R., Anfora, A. T., Liu, J., Schultz, P. G., Lesley, S. A., Peters, E. C., &

1830 Siuzdak, G. (2009). Metabolomics analysis reveals large effects of gut

1831 microflora on mammalian blood metabolites. *Proc Natl Acad Sci U S A,* 106,

1832 3698-3703.

1833 Williams, B. B., Van Benschoten, A. H., Cimermancic, P., Donia, M. S., Zimmermann,

1834 M., Taketani, M., Ishihara, A., Kashyap, P. C., Fraser, J. S., & Fischbach, M. A.

1835 (2014). Discovery and characterization of gut microbiota decarboxylases that

1836 can produce the neurotransmitter tryptamine. *Cell Host Microbe,* 16, 495-503.

1837 Windey, K., De Preter, V., Louat, T., Schuit, F., Herman, J., Vansant, G., & Verbeke,

1838 K. (2012). Modulation of protein fermentation does not affect fecal water

1839 toxicity: a randomized cross-over study in healthy subjects. *PLoS One,* 7,

1840 e52387.

1841 Wong, J., Piceno, Y. M., Desantis, T. Z., Pahl, M., Andersen, G. L., & Vaziri, N. D.

1842 (2014). Expansion of urease- and uricase-containing, indole- and p-cresol-

1843 forming and contraction of short-chain fatty acid-producing intestinal microbiota

1844 in ESRD. *Am J Nephrol,* 39, 230-237.

1845 Wu, G., Fanzo, J., Miller, D. D., Pingali, P., Post, M., Steiner, J. L., & Thalacker-

1846 Mercer, A. E. (2014). Production and supply of high-quality food protein for

1847 human consumption: sustainability, challenges, and innovations. *Ann N Y Acad

1848 *Sci,* 1321, 1-19.
1849 Wutzke, K. D., Lotz, M., & Zipprich, C. (2010). The effect of pre- and probiotics on the colonic ammonia metabolism in humans as measured by lactose-[¹⁵N₂]ureide. *Eur J Clin Nutr*, 64, 1215-1221.

1852 Wycherley, T. P., Moran, L. J., Clifton, P. M., Noakes, M., & Brinkworth, G. D. (2012). Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. *Am J Clin Nutr*, 96, 1281-1298.

1856 Xie, G., Keyhani, N. O., Bonner, C. A., & Jensen, R. A. (2003). Ancient origin of the tryptophan operon and the dynamics of evolutionary change. *Microbiol Mol Biol Rev*, 67, 303-342, table of contents.

1859 Xu, Y., Labedan, B., & Glansdorff, N. (2007). Surprising arginine biosynthesis: a reappraisal of the enzymology and evolution of the pathway in microorganisms. *Microbiol Mol Biol Rev*, 71, 36-47.

1862 Yamamoto, I., Saito, H., & Ishimoto, M. (1987). Regulation of synthesis and reversible inactivation *in vivo* of dual coenzyme-specific glutamate dehydrogenase in *Bacteroides fragilis*. *J Gen Microbiol*, 133, 2773-2780.

1865 Yamamoto, T., Hinoi, E., Fujita, H., Iezaki, T., Takahata, Y., Takamori, M., & Yoneda, Y. (2012). The natural polyamines spermidine and spermine prevent bone loss through preferential disruption of osteoclastic activation in ovariectomized mice. *Br J Pharmacol*, 166, 1084-1096.

1869 Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. *Cell*, 161, 264-276.
1849 Wutzke, K. D., Lotz, M., & Zipprich, C. (2010). The effect of pre- and probiotics on the colonic ammonia metabolism in humans as measured by lactose-[¹⁵N₂]ureide. *Eur J Clin Nutr*, 64, 1215-1221.

1852 Wycherley, T. P., Moran, L. J., Clifton, P. M., Noakes, M., & Brinkworth, G. D. (2012). Effects of energy-restricted high-protein, low-fat compared with standard-protein, low-fat diets: a meta-analysis of randomized controlled trials. *Am J Clin Nutr*, 96, 1281-1298.

1856 Xie, G., Keyhani, N. O., Bonner, C. A., & Jensen, R. A. (2003). Ancient origin of the tryptophan operon and the dynamics of evolutionary change. *Microbiol Mol Biol Rev*, 67, 303-342, table of contents.

1859 Xu, Y., Labedan, B., & Glansdorff, N. (2007). Surprising arginine biosynthesis: a reappraisal of the enzymology and evolution of the pathway in microorganisms. *Microbiol Mol Biol Rev*, 71, 36-47.

1862 Yamamoto, I., Saito, H., & Ishimoto, M. (1987). Regulation of synthesis and reversible inactivation *in vivo* of dual coenzyme-specific glutamate dehydrogenase in *Bacteroides fragilis*. *J Gen Microbiol*, 133, 2773-2780.

1865 Yamamoto, T., Hinoi, E., Fujita, H., Iezaki, T., Takahata, Y., Takamori, M., & Yoneda, Y. (2012). The natural polyamines spermidine and spermine prevent bone loss through preferential disruption of osteoclastic activation in ovariectomized mice. *Br J Pharmacol*, 166, 1084-1096.

1869 Yano, J. M., Yu, K., Donaldson, G. P., Shastri, G. G., Ann, P., Ma, L., Nagler, C. R., Ismagilov, R. F., Mazmanian, S. K., & Hsiao, E. Y. (2015). Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. *Cell*, 161, 264-276.
1872 Yu, L., Blaser, M., Andrei, P. I., Pierik, A. J., & Selmer, T. (2006). 4-Hydroxyphenylacetate decarboxylases: properties of a novel subclass of glycyl radical enzyme systems. *Biochemistry*, 45, 9584-9592.

1875 Yu, X. J., Walker, D. H., Liu, Y., & Zhang, L. (2009). Amino acid biosynthesis deficiency in bacteria associated with human and animal hosts. *Infect Genet Evol*, 9, 514-517.

1878 Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D'Angelo, C., Massi-Benedetti, C., Fallarino, F., Carvalho, A., Puccetti, P., & Romani, L. (2013). Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. *Immunity*, 39, 372-385.

1883

1884

1885

1886

1887

1888

1889

1890

1891

1892

1893

1894

1895

1896
1872 Yu, L., Blaser, M., Andrei, P. I., Pierik, A. J., & Selmer, T. (2006). 4-Hydroxyphenylacetate decarboxylases: properties of a novel subclass of glycyl radical enzyme systems. *Biochemistry*, 45, 9584-9592.

1875 Yu, X. J., Walker, D. H., Liu, Y., & Zhang, L. (2009). Amino acid biosynthesis deficiency in bacteria associated with human and animal hosts. *Infect Genet Evol*, 9, 514-517.

1878 Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D'Angelo, C., Massi-Benedetti, C., Fallarino, F., Carvalho, A., Puccetti, P., & Romani, L. (2013). Tryptophan catabolites from microbiota engage aryl hydrocarbon receptor and balance mucosal reactivity via interleukin-22. *Immunity*, 39, 372-385.

1883

1884

1885

1886

1887

1888

1889

1890

1891

1892

1893

1894

1895

1896
1897 **Figure Captions**

1898 **Figure 1: Prokaryotic biosynthetic enzymatic pathways of (A) glutamate and (B) serine amino acid families.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1899
1900
1901
1902
1903
1904

**Figure 2: Prokaryotic biosynthetic enzymatic pathways of the aspartic acid amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1905
1906
1907
1908
1909
1910
1911

**Figure 3: Prokaryotic biosynthetic enzymatic pathways of the pyruvate amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1912
1913
1914
1915
1916
1917
1918

**Figure 4: Prokaryotic biosynthetic enzymatic pathways of the aromatic acid amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1919
1920
1921

**Figure 4: Prokaryotic biosynthetic enzymatic pathways of the aromatic acid amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.
1897 **Figure Captions**

1898 **Figure 1: Prokaryotic biosynthetic enzymatic pathways of (A) glutamate and (B) serine amino acid families.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1899
1900
1901
1902
1903
1904

**Figure 2: Prokaryotic biosynthetic enzymatic pathways of the aspartic acid amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1905
1906
1907
1908
1909
1910
1911

**Figure 3: Prokaryotic biosynthetic enzymatic pathways of the pyruvate amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1912
1913
1914
1915
1916
1917
1918

**Figure 4: Prokaryotic biosynthetic enzymatic pathways of the aromatic acid amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1919
1920
1921

**Figure 4: Prokaryotic biosynthetic enzymatic pathways of the aromatic acid amino acid family.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.
1922 paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1925

1926 **Figure 5: Prokaryotic biosynthetic enzymatic pathway of histidine.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1927

1928

1929

1930

1931

1932

1933 **Figure 6: High protein diet effects with potential involvement of gut microbiota metabolism.** Left side: Peptides are degraded by the intestinal microbiota which release amino acid derived metabolites in the lumen. Gut bacteria can also produce amino acids. Right side: Host-functions affected by a high-protein diet demonstrated in human and animal studies (capital letters and bold). High protein diets increase the amount of protein available for fermentation by gut microbiota, which may mediate some of the effects of high protein diets on host physiology. Candidate bacterial amino acid derived metabolites for each effect of high protein diet are proposed. (Illustrations are from Servier Medical Art)

1934

1935

1936

1937

1938

1939

1940

1941

1942

1943 **Table 1: Gut microbiota-produced metabolites from amino acid catabolism that have potential effects on host physiology and health.** Genetic pathways for each metabolite are described along with enzymes and respective genes for each step in metabolic pathways. Gene names identified in the bacterium *E. coli* are highlighted in
1922 paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1925

1926 **Figure 5: Prokaryotic biosynthetic enzymatic pathway of histidine.** Enzymes with associated gene names compiled from the KEGG database are provided for each step in reaction pathways. Gene names include orthologous and paralogous gene groups among different bacterial taxa. Intermediate metabolites (yellow boxes) from the most common reaction pathways are provided for each end product amino acid (blue boxes) from each enzymatic family.

1927

1928

1929

1930

1931

1932

1933 **Figure 6: High protein diet effects with potential involvement of gut microbiota metabolism.** Left side: Peptides are degraded by the intestinal microbiota which release amino acid derived metabolites in the lumen. Gut bacteria can also produce amino acids. Right side: Host-functions affected by a high-protein diet demonstrated in human and animal studies (capital letters and bold). High protein diets increase the amount of protein available for fermentation by gut microbiota, which may mediate some of the effects of high protein diets on host physiology. Candidate bacterial amino acid derived metabolites for each effect of high protein diet are proposed. (Illustrations are from Servier Medical Art)

1934

1935

1936

1937

1938

1939

1940

1941

1942

1943 **Table 1: Gut microbiota-produced metabolites from amino acid catabolism that have potential effects on host physiology and health.** Genetic pathways for each metabolite are described along with enzymes and respective genes for each step in metabolic pathways. Gene names identified in the bacterium *E. coli* are highlighted in
1947 bold. Gene names include orthologous and paralogous gene groups among different

1948 bacterial taxa. All gene names are compiled from KEGG database except where noted.

1949 Amino acid abbreviations refer to glutamate (Glu); tryptophan (Tryp); histidine (His);

1950 tyrosine (Tyr); arginine (Arg); phenylalanine (Phe); cysteine (Cys); methionine (Met);

1951 lysine (Lys).
1947 bold. Gene names include orthologous and paralogous gene groups among different

1948 bacterial taxa. All gene names are compiled from KEGG database except where noted.

1949 Amino acid abbreviations refer to glutamate (Glu); tryptophan (Tryp); histidine (His);

1950 tyrosine (Tyr); arginine (Arg); phenylalanine (Phe); cysteine (Cys); methionine (Met);

1951 lysine (Lys).
<table><thead><tr><th>Metabolite</th><th>Amino Acid</th><th>Step</th><th>Substrate(s)</th><th>Product(s)</th><th>Enzyme (Enzyme Commission Number)</th><th>Gene(s)</th></tr></thead><tbody><tr><td colspan="7"><strong>Neuroactive compounds</strong></td></tr><tr><td>GABA</td><td>Glut</td><td>1</td><td>L-Glutamate</td><td>γ-Aminobutanoate, CO<sub>2</sub></td><td>Glutamate decarboxylase (4.1.1.15)</td><td>gadA, gadB</td></tr><tr><td>Serotonin (5-hydroxytryptamine)</td><td>Tryp</td><td>1</td><td>L-Tryptophan, Tetrahydrobiopterin, O<sub>2</sub></td><td>5-Hydroxy-L-tryptophan, Dihydrobiopterin, H<sub>2</sub>O</td><td>Tryptophan 5-monooxygenase (1.14.16.4)</td><td>No genes found in prokaryotes</td></tr><tr><td>Histamine (pathway 1)</td><td>His</td><td>1</td><td>L-Histidine</td><td>Serotonin, CO<sub>2</sub></td><td>Aromatic-L-amino-acid decarboxylase (4.1.1.28)</td><td>ddc, dcd, dcd1</td></tr><tr><td>Histamine (pathway 2)</td><td>His</td><td>1</td><td>L-Histidine</td><td>Histamine, CO<sub>2</sub></td><td>Histidine decarboxylase (4.1.1.22)</td><td>hdc, hdcA, angH, pmsA, basG, dchS, vlmD</td></tr><tr><td>L-DOPA</td><td>Tyr</td><td>1</td><td>L-Tyrosine, O<sub>2</sub></td><td>3,4-Dihydroxy-L-phenylalanine, (DOPA), H<sub>2</sub>O</td><td>Aromatic-L-amino-acid decarboxylase (4.1.1.28)</td><td>ddc, dcd1</td></tr><tr><td></td><td></td><td>2</td><td>2 N(ω)-Hydroxyarginine, NADH, H<sup>+</sup>,</td><td>2 Nitric oxide, 2 L-Citrulline,</td><td>Tyrosinase (1.14.18.1)</td><td>melO, melC1, melC2</td></tr></tbody></table>
<table><thead><tr><th>Metabolite</th><th>Amino Acid</th><th>Step</th><th>Substrate(s)</th><th>Product(s)</th><th>Enzyme (Enzyme Commission Number)</th><th>Gene(s)</th></tr></thead><tbody><tr><td colspan="7"><strong>Neuroactive compounds</strong></td></tr><tr><td>GABA</td><td>Glut</td><td>1</td><td>L-Glutamate</td><td>γ-Aminobutanoate, CO<sub>2</sub></td><td>Glutamate decarboxylase (4.1.1.15)</td><td>gadA, gadB</td></tr><tr><td>Serotonin (5-hydroxytryptamine)</td><td>Tryp</td><td>1</td><td>L-Tryptophan, Tetrahydrobiopterin, O<sub>2</sub></td><td>5-Hydroxy-L-tryptophan, Dihydrobiopterin, H<sub>2</sub>O</td><td>Tryptophan 5-monooxygenase (1.14.16.4)</td><td>No genes found in prokaryotes</td></tr><tr><td>Histamine (pathway 1)</td><td>His</td><td>1</td><td>L-Histidine</td><td>Serotonin, CO<sub>2</sub></td><td>Aromatic-L-amino-acid decarboxylase (4.1.1.28)</td><td>ddc, dcd, dcd1</td></tr><tr><td>Histamine (pathway 2)</td><td>His</td><td>1</td><td>L-Histidine</td><td>Histamine, CO<sub>2</sub></td><td>Histidine decarboxylase (4.1.1.22)</td><td>hdc, hdcA, angH, pmsA, basG, dchS, vlmD</td></tr><tr><td>L-DOPA</td><td>Tyr</td><td>1</td><td>L-Tyrosine, O<sub>2</sub></td><td>3,4-Dihydroxy-L-phenylalanine, (DOPA), H<sub>2</sub>O</td><td>Aromatic-L-amino-acid decarboxylase (4.1.1.28)</td><td>ddc, dcd1</td></tr><tr><td></td><td></td><td>2</td><td>2 N(ω)-Hydroxyarginine, NADH, H<sup>+</sup>,</td><td>2 Nitric oxide, 2 L-Citrulline,</td><td>Tyrosinase (1.14.18.1)</td><td>melO, melC1, melC2</td></tr></tbody></table>
<table><tbody><tr><td></td><td></td><td>O<sub>2</sub></td><td>NAD<sup>+</sup>, 2 H<sub>2</sub>O</td><td>(1.14.13.165)</td><td>sdaAB, txtD</td></tr><tr><td>Tyramine (pathway 1)</td><td>Tyr</td><td>1</td><td>L-Tyrosine</td><td>Tyramine, CO<sub>2</sub></td><td>Tyrosine decarboxylase<br>(4.1.1.25)</td></tr><tr><td>Tyramine (pathway 2)</td><td>Tyr</td><td>1</td><td>L-Tyrosine</td><td>Tyramine, CO<sub>2</sub></td><td>Aromatic-L-amino-acid<br>decarboxylase (4.1.1.28)</td></tr><tr><td>Nitric Oxide</td><td>Arg</td><td>1</td><td>L-Arginine, NADH (or NADPH), H<sup>+</sup>,<br>O<sub>2</sub></td><td>N(ω)-Hydroxyarginine, NAD<sup>+</sup><br>(or NADP<sup>+</sup>), H<sub>2</sub>O</td><td>Nitric-oxide synthase<br>(1.14.13.165)</td></tr><tr><td>Tryptamine</td><td>Tryp</td><td>1</td><td>L-Tryptophan</td><td>Tryptamine, CO<sub>2</sub></td><td>Aromatic-L-amino-acid<br>decarboxylase (4.1.1.28)</td></tr><tr><td>Phenylethylamine</td><td>Phe</td><td>1</td><td>L-Phenylalanine</td><td>Phenethylamine, CO<sub>2</sub></td><td>Aromatic-L-amino-acid<br>decarboxylase (4.1.1.28)</td></tr><tr><td colspan="6"><strong>Sulfide-containing metabolites</strong></td></tr><tr><td>H<sub>2</sub>S (pathway 1)</td><td>Cys</td><td>1</td><td>L-Cysteine, H<sub>2</sub>O</td><td>H<sub>2</sub>S, Pyruvate, Ammonia</td><td>Cysteine desulfhydrase<br>(4.4.1.1)</td></tr><tr><td>H<sub>2</sub>S (pathway 2)</td><td>Cys</td><td>1</td><td>L-Cysteine, H<sub>2</sub>O</td><td>H<sub>2</sub>S, Pyruvate, Ammonia</td><td>Cystathionine beta-lyase</td></tr></tbody></table>
<table><thead><tr><th></th><th></th><th></th><th></th><th></th><th></th><th></th></tr></thead><tbody><tr><td></td><td></td><td>O<sub>2</sub></td><td>NAD<sup>+</sup>, 2 H<sub>2</sub>O</td><td>(1.14.13.165)</td><td>sdaAB, txtD</td><td></td></tr><tr><td>Tyramine (pathway 1)</td><td>Tyr</td><td>1</td><td>L-Tyrosine</td><td>Tyramine, CO<sub>2</sub></td><td>Tyrosine decarboxylase<br>(4.1.1.25)</td><td>tyrDC, tdcA, mfnA,<br>mfnA, gadD, gadB</td></tr><tr><td>Tyramine (pathway 2)</td><td>Tyr</td><td>1</td><td>L-Tyrosine</td><td>Tyramine, CO<sub>2</sub></td><td>Aromatic-L-amino-acid<br>decarboxylase (4.1.1.28)</td><td>ddc, dcd, dcd1</td></tr><tr><td>Nitric Oxide</td><td>Arg</td><td>1</td><td>L-Arginine, NADH (or NADPH), H<sup>+</sup>,<br>O<sub>2</sub></td><td>N(ω)-Hydroxyarginine, NAD<sup>+</sup><br>(or NADP<sup>+</sup>), H<sub>2</sub>O</td><td>Nitric-oxide synthase<br>(1.14.13.165)</td><td>nos, nosA, yflM, rplB,<br>sdaAB, txtD</td></tr><tr><td>Tryptamine</td><td>Tryp</td><td>1</td><td>L-Tryptophan</td><td>Tryptamine, CO<sub>2</sub></td><td>Aromatic-L-amino-acid<br>decarboxylase (4.1.1.28)</td><td>ddc, dcd1, ddc</td></tr><tr><td>Phenylethylamine</td><td>Phe</td><td>1</td><td>L-Phenylalanine</td><td>Phenethylamine, CO<sub>2</sub></td><td>Aromatic-L-amino-acid<br>decarboxylase (4.1.1.28)</td><td>ddc, dcd1, ddc, tyrDC</td></tr><tr><td colspan="7"><strong>Sulfide-containing metabolites</strong></td></tr><tr><td>H<sub>2</sub>S (pathway 1)</td><td>Cys</td><td>1</td><td>L-Cysteine, H<sub>2</sub>O</td><td>H<sub>2</sub>S, Pyruvate, Ammonia</td><td>Cysteine desulfhydrase<br>(4.4.1.1)</td><td>cysA, metB, metC, yrhB,<br>mccB,</td></tr><tr><td>H<sub>2</sub>S (pathway 2)</td><td>Cys</td><td>1</td><td>L-Cysteine, H<sub>2</sub>O</td><td>H<sub>2</sub>S, Pyruvate, Ammonia</td><td>Cystathionine beta-lyase</td><td>metC, metB, malY, patB</td></tr></tbody></table>
<table><tbody><tr><td>Methanethiol</td><td>Met</td><td>1</td><td>L-Methionine, H<sub>2</sub>O</td><td>Methanethiol, Ammonia, 2-Oxobutanoate</td><td>Methionine-gamma-lyase<br>(4.4.1.11)</td><td>mdeA, megL, metB, metZ</td></tr><tr><td colspan="7"><strong>Aromatic compounds</strong></td></tr><tr><td>Phenol</td><td>Tyr</td><td>1</td><td>L-Tyrosine, H<sub>2</sub>O</td><td>Phenol, Pyruvate, Ammonia</td><td>Tyrosine phenol-lyase<br>(4.1.99.2)</td><td>tpl</td></tr><tr><td>p-cresol</td><td>Tyr</td><td>1</td><td>L-Tyrosine</td><td>unknown</td><td>unknown</td><td>Pathway unknown<br>(Dawson et al., 2011)</td></tr><tr><td></td><td></td><td>2</td><td>unknown</td><td>unknown</td><td>unknown</td><td></td></tr><tr><td></td><td></td><td>3</td><td>4-hydroxyphenylacetate, H<sup>+</sup></td><td>4-methylphenol (p-cresol), CO<sub>2</sub></td><td>4-hydroxyphenylacetate<br>decarboxylase (4.1.1.83)</td><td>hpdB, hpdC, hpdA (Yu<br>et al., 2006)</td></tr><tr><td>Indole</td><td>Tryp</td><td>1</td><td>L-Tryptophan, H<sub>2</sub>O</td><td>Indole, Pyruvate, Ammonia</td><td>Tryptophanase (4.1.99.1)</td><td>tnaA</td></tr><tr><td colspan="7"><strong>Polyamines</strong></td></tr><tr><td>Agmatine</td><td>Arg</td><td>1</td><td>L-Arginine</td><td>Agmatine, CO<sub>2</sub></td><td>Arginine decarboxylase<br>(4.1.1.19)</td><td>speA, adiA, cad, pdaD,<br>aaxB</td></tr><tr><td>Putrescine (pathway 1)</td><td>Arg</td><td>1</td><td>L-Arginine</td><td>Agmatine, CO<sub>2</sub></td><td>Arginine decarboxylase</td><td>speA, adiA, cad, pdaD,</td></tr></tbody></table>
<table><tbody><tr><td>Methanethiol</td><td>Met</td><td>1</td><td>L-Methionine, H₂O</td><td>Methanethiol, Ammonia, 2-Oxobutanoate</td><td>Methionine-gamma-lyase<br>(4.4.1.11)</td><td>mdeA, megL, metB, metZ</td></tr><tr><td colspan="7"><strong>Aromatic compounds</strong></td></tr><tr><td>Phenol</td><td>Tyr</td><td>1</td><td>L-Tyrosine, H₂O</td><td>Phenol, Pyruvate, Ammonia</td><td>Tyrosine phenol-lyase<br>(4.1.99.2)</td><td>tpl</td></tr><tr><td>p-cresol</td><td>Tyr</td><td>1</td><td>L-Tyrosine</td><td>unknown</td><td>unknown</td><td>Pathway unknown<br>(Dawson et al., 2011)</td></tr><tr><td></td><td></td><td>2</td><td>unknown</td><td>unknown</td><td>unknown</td><td></td></tr><tr><td></td><td></td><td>3</td><td>4-hydroxyphenylacetate, H⁺</td><td>4-methylphenol (p-cresol), CO₂</td><td>4-hydroxyphenylacetate<br>decarboxylase (4.1.1.83)</td><td>hpdB, hpdC, hpdA (Yu<br>et al., 2006)</td></tr><tr><td>Indole</td><td>Tryp</td><td>1</td><td>L-Tryptophan, H₂O</td><td>Indole, Pyruvate, Ammonia</td><td>Tryptophanase (4.1.99.1)</td><td>tnaA</td></tr><tr><td colspan="7"><strong>Polyamines</strong></td></tr><tr><td>Agmatine</td><td>Arg</td><td>1</td><td>L-Arginine</td><td>Agmatine, CO₂</td><td>Arginine decarboxylase<br>(4.1.1.19)</td><td>speA, adiA, cad, pdaD,<br>aaxB</td></tr><tr><td>Putrescine (pathway 1)</td><td>Arg</td><td>1</td><td>L-Arginine</td><td>Agmatine, CO₂</td><td>Arginine decarboxylase</td><td>speA, adiA, cad, pdaD,</td></tr></tbody></table>
<table><tbody><tr><td></td><td></td><td>2</td><td>Agmatine, H<sub>2</sub>O</td><td>Putrescine, Urea</td><td>Agmatinase (3.5.3.11)<br>(4.1.1.19)</td><td>aaxB<br>speB, speB1, speB2, pah, gbh</td></tr><tr><td rowspan="3">Putrescine (pathway 2)</td><td rowspan="3">Arg</td><td>1</td><td>L-Arginine</td><td>Agmatine, CO<sub>2</sub></td><td>Arginine decarboxylase<br>(4.1.1.19)</td><td>speA, adiA, cad, pdaD, aaxB</td></tr><tr><td>2</td><td>Agmatine, H<sub>2</sub>O</td><td>N-Carbamoylputrescine,<br>Ammonia</td><td>Agmatine deiminase<br>(3.5.3.12)</td><td>aguA, aguA1, aguA2</td></tr><tr><td>3</td><td>N-Carbamoylputrescine, H<sub>2</sub>O</td><td>Putrescine, CO<sub>2</sub>, Ammonia</td><td>N-carbamoylputrescine<br>amidase (3.5.1.53)</td><td>aguB</td></tr><tr><td rowspan="2">Putrescine (pathway 3)</td><td rowspan="2">Arg</td><td>1</td><td>L-Arginine, H<sub>2</sub>O</td><td>L-Ornithine, Urea</td><td>Arginase (3.5.3.1)</td><td>rocF</td></tr><tr><td>2</td><td>L-Ornithine</td><td>Putrescine, CO<sub>2</sub></td><td>Ornithine decarboxylase<br>(4.1.1.17)</td><td>speC, speF</td></tr><tr><td>Spermidine (pathway 1)</td><td>Arg</td><td>1</td><td>S-Adenosylmethioninamine,<br>putrescine</td><td>5'-Methylthioadenosine,<br>Spermidine</td><td>Spermidine synthase<br>(2.5.1.16)</td><td>speE</td></tr><tr><td rowspan="2">Spermidine (pathway 2)</td><td rowspan="2">Arg</td><td>1</td><td>L-aspartate 4-semialdehyde,<br>putrescine, NADPH, H<sup>+</sup></td><td>carboxyspermidine, H<sub>2</sub>O,<br>NADP<sup>+</sup></td><td>Carboxynorspermidine<br>synthase (1.5.1.43)</td><td>cansdh</td></tr><tr><td>2</td><td>carboxyspermidine</td><td>spermidine, CO<sub>2</sub></td><td>Carboxynorspermidine<br>decarboxylase (4.1.1.96)</td><td>nspC, cansdc</td></tr></tbody></table>
<table><tbody><tr><td></td><td></td><td>2</td><td>Agmatine, H<sub>2</sub>O</td><td>Putrescine, Urea</td><td>Agmatinase (3.5.3.11)<br>(4.1.1.19)</td><td>aaxB<br>speB, speB1, speB2, pah, gbh</td></tr><tr><td rowspan="3">Putrescine (pathway 2)</td><td rowspan="3">Arg</td><td>1</td><td>L-Arginine</td><td>Agmatine, CO<sub>2</sub></td><td>Arginine decarboxylase<br>(4.1.1.19)</td><td>speA, adiA, cad, pdaD, aaxB</td></tr><tr><td>2</td><td>Agmatine, H<sub>2</sub>O</td><td>N-Carbamoylputrescine,<br>Ammonia</td><td>Agmatine deiminase<br>(3.5.3.12)</td><td>aguA, aguA1, aguA2</td></tr><tr><td>3</td><td>N-Carbamoylputrescine, H<sub>2</sub>O</td><td>Putrescine, CO<sub>2</sub>, Ammonia</td><td>N-carbamoylputrescine<br>amidase (3.5.1.53)</td><td>aguB</td></tr><tr><td rowspan="2">Putrescine (pathway 3)</td><td rowspan="2">Arg</td><td>1</td><td>L-Arginine, H<sub>2</sub>O</td><td>L-Ornithine, Urea</td><td>Arginase (3.5.3.1)</td><td>rocF</td></tr><tr><td>2</td><td>L-Ornithine</td><td>Putrescine, CO<sub>2</sub></td><td>Ornithine decarboxylase<br>(4.1.1.17)</td><td>speC, speF</td></tr><tr><td>Spermidine (pathway 1)</td><td>Arg</td><td>1</td><td>S-Adenosylmethioninamine,<br>putrescine</td><td>5'-Methylthioadenosine,<br>Spermidine</td><td>Spermidine synthase<br>(2.5.1.16)</td><td>speE</td></tr><tr><td rowspan="2">Spermidine (pathway 2)</td><td rowspan="2">Arg</td><td>1</td><td>L-aspartate 4-semialdehyde,<br>putrescine, NADPH, H<sup>+</sup></td><td>carboxyspermidine, H<sub>2</sub>O,<br>NADP<sup>+</sup></td><td>Carboxynorspermidine<br>synthase (1.5.1.43)</td><td>cansdh</td></tr><tr><td>2</td><td>carboxyspermidine</td><td>spermidine, CO<sub>2</sub></td><td>Carboxynorspermidine<br>decarboxylase (4.1.1.96)</td><td>nspC, cansdc</td></tr></tbody></table>
<table><tr><td>Spermine</td><td>Arg 1</td><td>S-Adenosylmethioninamine, Spermidine</td><td>5'-Methylthioadenosine, Spermine</td><td>Spermine synthase (2.5.1.22)</td><td>SMS (not found in prokaryotes)</td></tr><tr><td>Cadaverine</td><td>Lys 1</td><td>L-Lysine</td><td>Cadaverine, CO<sub>2</sub></td><td>Lysine decarboxylase (4.1.1.18)</td><td>ldcC, cadA, speA, cad</td></tr></table>
<table><tr><td>Spermine</td><td>Arg 1</td><td>S-Adenosylmethioninamine, Spermidine</td><td>5'-Methylthioadenosine, Spermine</td><td>Spermine synthase (2.5.1.22)</td><td>SMS (not found in prokaryotes)</td></tr><tr><td>Cadaverine</td><td>Lys 1</td><td>L-Lysine</td><td>Cadaverine, CO<sub>2</sub></td><td>Lysine decarboxylase (4.1.1.18)</td><td>ldcC, cadA, speA, cad</td></tr></table>
1953
1953