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von Martels, J. Z., Sadabad, M. S., Bourgonje, A. R., Blokzijl, T., Dijkstra, G., Faber, K. N., et al. (2017). The role of gut microbiota in health and disease: *in vitro* modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut. *Anaerobe* 44, 3–12. doi: 10.1016/j.anaerobe.2017.01.001

von Martels, J. Z. H. (2019). *Towards Novel Biomarkers And Rational Nutritional Interventions In Inflammatory Bowel Disease*. Groningen: University of Groningen.

Vrancken, G., Gregory, A. C., Huys, G. R., Faust, K., and Raes, J. (2019). Synthetic ecology of the human gut microbiota. *Nat. Rev. Microbiol.* 17, 754–763. doi: 10.1038/s41579-019-0264-8

Walsh, J., Griffin, B. T., Clarke, G., and Hyland, N. P. (2018). Drug–gut microbiota interactions: implications for neuropharmacology. *Br. J. Pharmacol.* 175, 4415– 4429. doi: 10.1111/bph.14366

Wang, Y., Lv, Y., Cai, J., Schwarz, S., Cui, L., Hu, Z., et al. (2015). A novel gene, optrA, that confers transferable resistance to oxazolidinones and phenicols and its presence in *Enterococcus faecalis* and *Enterococcus faecium* of human and animal origin. *J. Antimicrob. Chemother.* 70, 2182–2190. doi: 10.1093/jac/ dky116

Wasielewski, H., Alcock, J., and Aktipis, A. (2016). Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health. *Ann. N. Y. Acad. Sci.* 1372, 20–28. doi: 10.1111/nyas.13118

Whittle, G., Shoemaker, N. B., and Salyers, A. A. (2002). The role of *Bacteroides* conjugative transposons in the dissemination of antibiotic resistance genes. *Cell. Mol. Life Sci.* 59, 2044–2054. doi: 10.1007/s00018020004

Wilson, I. D., and Nicholson, J. K. (2017). Gut microbiome interactions with drug metabolism, efficacy, and toxicity. *Transl. Res.* 179, 204–222. doi: 10.1016/j.trsl. 2016.08.002

Yaffe, E., and Relman, D. A. (2020). Tracking microbial evolution in the human gut using Hi-C reveals extensive horizontal gene transfer, persistence and adaptation. *Nat. Microbiol.* 5, 343–353. doi: 10.1038/s41564-019-0625-0

Zihler, A., Gagnon, M., Chassard, C., Hegland, A., Stevens, M. J., Braegger, C. P., et al. (2010). Unexpected consequences of administering bacteriocinogenic probiotic strains for *Salmonella* populations, revealed by an *in vitro* colonic model of the child gut. *Microbiology* 156, 3342–3353. doi: 10.1099/mic.0. 042036-0

Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R., and Goodman, A. L. (2019). Mapping human microbiome drug metabolism by gut bacteria and their genes. *Nature* 570, 462–467. doi: 10.1038/s41586-019-1291-3

Zou, L., Spanogiannopoulos, P., Pieper, L. M., Chien, H.-C., Cai, W., Khuri, N., et al. (2020). Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives. *Proc. Natl. Acad. Sci.* 117, 16009–16018. doi: 10.1073/pnas.1920483117
Schumacher, U. K., and Single, B. (1998). Susceptibility of the anaerobic gram-negative non-sporulating rod, *Bilophila wadsworthia* to beta-lactams, beta-lactamase inhibitors, meropenem, metronidaz. *Zentralblatt Für Bakteriol.* 287, 421-425. doi: 10.1016/S0934-8840(98)80179-5

Selber-Hnatiw, S., Sultana, T., Tse, W., Abdollahi, N., Abdullah, S., Al Rahbani, J., et al. (2020). Metabolic networks of the human gut microbiota. *Microbiology* 166, 96-119. doi: 10.1099/mic.0.000853

Senghor, B., Sokhna, C., Ruimy, R., and Lagier, J.-C. (2018). Gut microbiota diversity according to dietary habits and geographical provenance. *Hum. Microbiome J.* 8, 1-9. doi: 10.1016/j.humic.2018.01.001

Shah, P., Fritz, J. V., Glaab, E., Desai, M. S., Greenhalgh, K., Frachet, A., et al. (2016). A microfluidics-based *in vitro* model of the gastrointestinal human–microbe interface. *Nat. Commun.* 7, 1–15. doi: 10.1038/ncomms11535

Shen, Z.-H., Zhu, C.-X., Quan, Y.-S., Yang, Z.-Y., Wu, S., Luo, W.-W., et al. (2018). Relationship between intestinal microbiota and ulcerative colitis: mechanisms and clinical application of probiotics and fecal microbiota transplantation. *World J. Gastroenterol.* 24, 5–14. doi: 10.3748/wjg.v24.i1.5

Silverman, J. D., Durand, H. K., Bloom, R. J., Mukherjee, S., and David, L. A. (2018). Dynamic linear models guide design and analysis of microbiota studies within artificial human guts. *Microbiome* 6, 1–20.

Singh, S. B., Young, K., and Silver, L. L. (2017). What is an “ideal” antibiotic? Discovery challenges and path forward. *Biochem. Pharmacol.* 133, 63–73. doi: 10.1016/j.bcp.2017.01.003

Song, Y., Liu, C., Lee, J., Bolaños, M., Vaisanen, M.-L., and Finegold, S. M. (2005). *Bacteroides goldsteinii* sp. nov." Isolated from clinical specimens of human intestinal origin. *J. Clin. Microbiol.* 43, 4522–4527. doi: 10.1128/JCM.43.9.4522-4527.2005

Sousa, T., Paterson, R., Moore, V., Carlsson, A., Abrahamsson, B., and Basit, A. W. (2008). The gastrointestinal microbiota as a site for the biotransformation of drugs. *Int. J. Pharm.* 363, 1–25. doi: 10.1016/j.ijpharm.2008.07.009

Stojanov, S., Berlec, A., and Strukelj, B. (2020). The influence of probiotics on the *Firmicutes/Bacteroidetes* ratio in the treatment of obesity and inflammatory bowel disease. *Microorganisms* 8:1715. doi: 10.3390/microorganisms811715

Sun, C., Chen, L., and Shen, Z. (2019). Mechanisms of gastrointestinal microflora on drug metabolism in clinical practice. *Saudi Pharm. J.* 27, 1146–1156. doi: 10.1016/j.jpaps.2019.09.011

Sung, J., Kim, S., Cabatbat, J. J. T., Jang, S., Jin, Y.-S., Jung, G. Y., et al. (2017). Global metabolic interaction network of the human gut microbiota for context-specific community-scale analysis. *Nat. Commun.* 8, 1–12. doi: 10.1038/ncomms153 93

Tap, J., Mondot, S., Levenez, F., Pelletier, E., Caron, C., Furet, J.-P., et al. (2009). Towards the human intestinal microbiota phylogenetic core. *Environ. Microbiol.* 11, 2574–2584. doi: 10.1111/j.1462-2920.2009.01982.x

Teng, L.-J., Hsueh, P.-R., Tsai, J.-C., Liaw, S.-J., Ho, S.-W., and Luh, K.-T. (2002). High incidence of cefoxitin and clindamycin resistance among anaerobes in Taiwan. *Antimicrob. Agents Chemother.* 46, 2908–2913. doi: 10.1128/AAC.46. 9.2908-2913.2002

Tilkorn, F. K. M. T., Frickmann, H., Simon, I. S., Schwanbeck, J., Horn, S., Zimmermann, O., et al. (2020). Antimicrobial resistance patterns in *Clostridioides difficile* strains isolated from neonates in Germany. *Antibiotics* 9:481. doi: 10.3390/antibiotics9080481

Tobío, M., Sánchez, A., Vila, A., Soriano, I., Evora, C., Vila-Jato, J. L., et al. (2000). The role of PEG on the stability in digestive fluids and *in vivo* fate of PEG-PLA nanoparticles following oral administration. *Colloids Surf. B Biointerfaces* 18, 315-323. doi: 10.1016/S0927-7765(99)00157-5

Tramontano, M., Andrejev, S., Pruteanu, M., Klünemann, M., Kuhn, M., Galardini, M., et al. (2018). Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies. *Nat. Microbiol.* 3, 514–522. doi: 10.1038/s41564-018- 0123-9

Tsang, J. O.-L., Zhou, J., Zhao, X., Li, C., Zou, Z., Yin, F., et al. (2021). Development of three-dimensional human intestinal organoids as a physiologically relevant model for characterizing the viral replication kinetics and antiviral susceptibility of enteroviruses. *Biomedicines* 9:88. doi: 10.3390/biomedicines90100 88

Tsitko, I., Wiik-Miettinen, F., Mattila, O., Rosa-Sibakov, N., Seppänen-Laakso, T., Maukonen, J., et al. (2019). A small *in vitro* fermentation model for screening the gut microbiota effects of different fiber preparations. *Int. J. Mol. Sci.* 20:1925. doi: 10.3390/ijms20081925

Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., et al. (2009). A core gut microbiome in obese and lean twins. *Nature* 457, 480–484. doi: 10.1038/nature07540

Uzigai, N., Murakami, K., Ulit, M. V., Antonio, L. S., Shirotori, M., Morikawa, H., et al. (2011). The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration. *Phytomedicine* 18, 575–578. doi: 10.1016/j.phymed.2010.10.019

Van den Abbeele, P., Grootaert, C., Marzorati, M., Possemiers, S., Verstraete, W., Gérard, P., et al. (2010). Microbial community development in a dynamic gut model is reproducible, colon region specific, and selective for Bacteroidetes and *Clostridium* cluster IX. *Appl. Environ. Microbiol.* 76, 5237–5246. doi: 10.1128/AEM.00759-10

Venema, K., and Van den Abbeele, P. (2013). Experimental models of the gut microbiome. *Best Pract. Res. Clin. Gastroenterol.* 27, 115–126. doi: 10.1016/j. bpg.2013.03.002

Venturelli, O. S., Carr, A. C., Fisher, G., Hsu, R. H., Lau, R., Bowen, B. P., et al. (2018). Deciphering microbial interactions in synthetic human gut microbiome communities. *Mol. Syst. Biol.* 14:e8157. doi: 10.15252/msb.20178157

Vich Vila, A., Collij, V., Sanna, S., Sinha, T., Imhann, F., Bourgonje, A. R., et al. (2020). Impact of commonly used drugs on the composition and metabolic function of the gut microbiota. *Nat. Commun.* 11, 1–11. doi: 10.1038/s41467- 019-14177-z

Villa, M. M., Bloom, R. J., Silverman, J. D., Durand, H. K., Jiang, S., Wu, A., et al. (2020). Interindividual variation in dietary carbohydrate metabolism by gut Bacteria revealed with droplet microfluidic culture. *M systems* 5:e0864-19. doi: 10.1128/mSystems.00864-19

von Martels, J. Z., Sadabad, M. S., Bourgonje, A. R., Blokzijl, T., Dijkstra, G., Faber, K. N., et al. (2017). The role of gut microbiota in health and disease: *in vitro* modeling of host-microbe interactions at the aerobe-anaerobe interphase of the human gut. *Anaerobe* 44, 3–12. doi: 10.1016/j.anaerobe.2017.01.001

von Martels, J. Z. H. (2019). *Towards Novel Biomarkers And Rational Nutritional Interventions In Inflammatory Bowel Disease*. Groningen: University of Groningen.

Vrancken, G., Gregory, A. C., Huys, G. R., Faust, K., and Raes, J. (2019). Synthetic ecology of the human gut microbiota. *Nat. Rev. Microbiol.* 17, 754–763. doi: 10.1038/s41579-019-0264-8

Walsh, J., Griffin, B. T., Clarke, G., and Hyland, N. P. (2018). Drug–gut microbiota interactions: implications for neuropharmacology. *Br. J. Pharmacol.* 175, 4415– 4429. doi: 10.1111/bph.14366

Wang, Y., Lv, Y., Cai, J., Schwarz, S., Cui, L., Hu, Z., et al. (2015). A novel gene, *optrA*, that confers transferable resistance to oxazolidinones and phenicols and its presence in *Enterococcus faecalis* and *Enterococcus faecium* of human and animal origin. *J. Antimicrob. Chemother.* 70, 2182–2190. doi: 10.1093/jac/ dky116

Wasielewski, H., Alcock, J., and Aktipis, A. (2016). Resource conflict and cooperation between human host and gut microbiota: implications for nutrition and health. *Ann. N. Y. Acad. Sci.* 1372, 20–28. doi: 10.1111/nyas.13118

Whittle, G., Shoemaker, N. B., and Salyers, A. A. (2002). The role of *Bacteroides* conjugative transposons in the dissemination of antibiotic resistance genes. *Cell. Mol. Life Sci.* 59, 2044–2054. doi: 10.1007/s00018020004

Wilson, I. D., and Nicholson, J. K. (2017). Gut microbiome interactions with drug metabolism, efficacy, and toxicity. *Transl. Res.* 179, 204–222. doi: 10.1016/j.trsl. 2016.08.002

Yaffe, E., and Relman, D. A. (2020). Tracking microbial evolution in the human gut using Hi-C reveals extensive horizontal gene transfer, persistence and adaptation. *Nat. Microbiol.* 5, 343–353. doi: 10.1038/s41564-019-0625-0

Zihler, A., Gagnon, M., Chassard, C., Hegland, A., Stevens, M. J., Braegger, C. P., et al. (2010). Unexpected consequences of administering bacteriocinogenic probiotic strains for *Salmonella* populations, revealed by an *in vitro* colonic model of the child gut. *Microbiology* 156, 3342–3353. doi: 10.1099/mic.0. 042036-0

Zimmermann, M., Zimmermann-Kogadeeva, M., Wegmann, R., and Goodman, A. L. (2019). Mapping human microbiome drug metabolism by gut bacteria and their genes. *Nature* 570, 462–467. doi: 10.1038/s41586-019-1291-3

Zou, L., Spanogiannopoulos, P., Pieper, L. M., Chien, H.-C., Cai, W., Khuri, N., et al. (2020). Bacterial metabolism rescues the inhibition of intestinal drug absorption by food and drug additives. *Proc. Natl. Acad. Sci.* 117, 16009–16018. doi: 10.1073/pnas.1920483117
Zuo, T., Wong, S. H., Cheung, C. P., Lam, K., Lui, R., Cheung, K., et al. (2018). Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in *Clostridium difficile* infection. *Nat. Commun.* 9, 1–11. doi: 10.1038/s41467-018-06103-6

**Conflict of Interest:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

**Publisher's Note:** All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of

the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Copyright © 2022 El Houari, Ecale, Mercier, Crapart, Laparre, Soulard, Ramnath, Berjeaud, Rodier and Crépin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Zuo, T., Wong, S. H., Cheung, C. P., Lam, K., Lui, R., Cheung, K., et al. (2018). Gut fungal dysbiosis correlates with reduced efficacy of fecal microbiota transplantation in *Clostridium difficile* infection. *Nat. Commun.* 9, 1–11. doi: 10.1038/s41467-018-06103-6

**Conflict of Interest:** The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

**Publisher's Note:** All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of

the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Copyright © 2022 El Houari, Ecale, Mercier, Crapart, Laparre, Soulard, Ramnath, Berjeaud, Rodier and Crépin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.