<figure><img src="image_77.png" /></figure>

7. Bradley KC, Finsterbusch K, Schnepf D, Crotta S, Llorian M, Davidson S, Fuchs SY, Staeheli P, Wack A. Microbiota-driven tonic interferon signals in lung stromal cells protect from influenza virus infection. Cell Rep. 2019;28(1):245-256.e4. doi:10.1016/j.celrep.2019.05.105.

8. Stefan KL, Kim MV, Iwasaki A, Kasper DL. Commensal microbiota modulation of natural resistance to virus infection. Cell. 2020;183(5):1312-1324.e10. doi:10.1016/j.cell.2020.10.047.

9. Wang J, Li F, Wei H, Lian Z-X, Sun R, Tian Z. Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation. J Exp Med. 2014;211(12):2397-2410. doi:10.1084/jem.20140625.

10. Deriu E, Boxx GM, He X, Pan C, Benavidez SD, Cen L, Rozengurt N, Shi W, Cheng G, Tsolis RM. Influenza virus affects intestinal microbiota and secondary salmonella infection in the gut through type I interferons. PloS Pathog. 2016;12(5):e1005572. doi:10.1371/journal.ppat.1005572.

11. Yildiz S, Mazel-Sanchez B, Kandasamy M, Manicassamy B, Schmolke M. Influenza a virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis. Microbiome. 2018;6(1):9. doi:10.1186/s40168-017-0386-z.

12. Sencio V, Barthelemy A, Tavares LP, Machado MG, Soulard D, Cuinat C, Queiroz-Junior CM, Noordine M-L, Salomé-Desnoulez S, Deryuter L. et al. Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production. Cell Rep. 2020;30(9):2934-2947.e6. doi:10.1016/j.celrep.2020.02.013.

13. Hu X, Zhao Y, Yang Y, Gong W, Sun X, Yang L, Zhang Q, Jin M. Akkermansia muciniphila improves host defense against influenza virus infection. Front Microbiol. 2020;11:586476. doi:10.3389/fmicb.2020.586476.

14. Zhang Q, Hu J, Feng J-W, Hu X-T, Wang T, Gong W-X, Huang K, Guo Y-X, Zou Z, Lin X. et al. Influenza infection elicits an expansion of gut population of endogenous bifidobacterium animalis which protects mice against infection. Genome Biol. 2020;21(1):99. doi:10.1186/s13059-020-02007-1.

15. Gierse LC, Meene A, Schultz D, Schwaiger T, Schröder C, Mücke P, Zühlke D, Hinzke T, Wang H, Methling K. et al. Influenza a H1N1 induced disturbance of the respiratory and fecal microbiome of German landrace pigs - a multi-omics characterization. Microbiol Spectr. 2021;9(2):e00182-21. doi:10.1128/Spectrum.00182-21.

16. Sencio V, Gallerand A, Machado MG, Deruyter L, Heumel S, Soulard D, Barthelemy J, Cuinat C, Vieira AT, Barthelemy A. et al. Influenza virus infection impairs the gut's barrier properties and favors secondary enteric bacterial infection through reduced

production of short-chain fatty acids. Infect Immun. 2021;89(9). doi:10.1128/IAI.00734-20.

17. Qin N, Zheng B, Yao J, Guo L, Zuo J, Wu L, Zhou J, Liu L, Guo J, Ni S. et al. Influence of H7N9 virus infection and associated treatment on human gut microbiota. Sci Rep. 2015;5(1):14771. doi:10.1038/srep14771.

18. Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, Guo F, Zhang X, Luo R, Huang C. et al. Alterations of the gut microbiota in patients with coronavirus disease 2019 or H1N1 influenza. Clin Infect Dis. 2020;71(10):2669-2678. doi:10.1093/cid/ciaa709.

19. Al Khatib HA, Mathew S, Smatti MK, Eltai NO, Pathan SA, Al Thani AA, Coyle PV, Al Maslamani MA, Yassine HM. Profiling of intestinal microbiota in patients infected with respiratory influenza a and B viruses. Pathogens. 2021;10(6):761. doi:10.3390/pathogens10060761.

20. Fuentes S, den Hartog G, Nanlohy NM, Wijnands L, Ferreira JA, Nicolaie MA, Pennings JLA, Jacobi R, de Wit J, van Beek J. et al. Associations of faecal microbiota with influenza-like illness in participants aged 60 years or older: an observational study. Lancet Healthy Longevi. 2021;2(1):e13-e23. doi:10.1016/S2666-7568(20)30034-9.

21. Tessler M, Neumann JS, Afshinnekoo E, Pineda M, Hersch R, Velho LFM, Segovia BT, Lansac-Toha FA, Lemke M, DeSalle R. et al. Large-scale differences in microbial biodiversity discovery between 16S amplicon and shotgun sequencing. Sci Rep. 2017;7(1):6589. doi:10.1038/s41598-017-06665-3.

22. Brumfield KD, Huq A, Colwell RR, Olds JL, Leddy MB, Gyarmati P. Microbial resolution of whole genome shotgun and 16S amplicon metagenomic sequencing using publicly available NEON data. PLoS One. 2020;15(2):e0228899. doi:10.1371/journal.pone.0228899.

23. Nayfach S, Pollard KS. Toward accurate and quantitative comparative metagenomics. Cell. 2016;166(5):1103-1116. doi:10.1016/j.cell.2016.08.007.

24. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of akkermansia muciniphila. Front Microbiol. 2017;8:1765. doi:10.3389/fmicb.2017.01765.

25. Aramaki T, Blanc-Mathieu R, Endo H, Ohkubo K, Kanehisa M, Goto S, Ogata H, Valencia A. KofamKOALA: KEGG ortholog assignment based on profile HMM and adaptive score threshold. Bioinformatics. 2020;36(7):2251-2252. doi:10.1093/bioinformatics/btz859.

26. Trompette A, Gollwitzer ES, Pattaroni C, Lopez-Mejia IC, Riva E, Pernot J, Ubags N, Fajas L, Nicod LP, Marsland BJ. Dietary fiber confers protection against flu by shaping Ly6c+ patrolling monocyte hematopoiesis and CD8+ T cell metabolism. Immunity. 2018;48(5):992-1005.e8. doi:10.1016/j.immuni.2018.04.022.

27. Gowda D, Li Y, Gowda B, Ohno SG, Chiba M, H Hui S-P. Determination of short-chain fatty acids by N,N-dimethylethylenediamine derivatization combined with liquid chromatography/mass spectrometry
<figure><img src="image_76.png" /></figure>

7. Bradley KC, Finsterbusch K, Schnepf D, Crotta S, Llorian M, Davidson S, Fuchs SY, Staeheli P, Wack A. Microbiota-driven tonic interferon signals in lung stromal cells protect from influenza virus infection. Cell Rep. 2019;28(1):245-256.e4. doi:10.1016/j.celrep.2019.05.105.

8. Stefan KL, Kim MV, Iwasaki A, Kasper DL. Commensal microbiota modulation of natural resistance to virus infection. Cell. 2020;183(5):1312-1324.e10. doi:10.1016/j.cell.2020.10.047.

9. Wang J, Li F, Wei H, Lian Z-X, Sun R, Tian Z. Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation. J Exp Med. 2014;211(12):2397-2410. doi:10.1084/jem.20140625.

10. Deriu E, Boxx GM, He X, Pan C, Benavidez SD, Cen L, Rozengurt N, Shi W, Cheng G, Tsolis RM. Influenza virus affects intestinal microbiota and secondary salmonella infection in the gut through type I interferons. PloS Pathog. 2016;12(5):e1005572. doi:10.1371/journal.ppat.1005572.

11. Yildiz S, Mazel-Sanchez B, Kandasamy M, Manicassamy B, Schmolke M. Influenza a virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis. Microbiome. 2018;6(1):9. doi:10.1186/s40168-017-0386-z.

12. Sencio V, Barthelemy A, Tavares LP, Machado MG, Soulard D, Cuinat C, Queiroz-Junior CM, Noordine M-L, Salomé-Desnoulez S, Deryuter L. et al. Gut dysbiosis during influenza contributes to pulmonary pneumococcal superinfection through altered short-chain fatty acid production. Cell Rep. 2020;30(9):2934-2947.e6. doi:10.1016/j.celrep.2020.02.013.

13. Hu X, Zhao Y, Yang Y, Gong W, Sun X, Yang L, Zhang Q, Jin M. Akkermansia muciniphila improves host defense against influenza virus infection. Front Microbiol. 2020;11:586476. doi:10.3389/fmicb.2020.586476.

14. Zhang Q, Hu J, Feng J-W, Hu X-T, Wang T, Gong W-X, Huang K, Guo Y-X, Zou Z, Lin X. et al. Influenza infection elicits an expansion of gut population of endogenous bifidobacterium animalis which protects mice against infection. Genome Biol. 2020;21(1):99. doi:10.1186/s13059-020-02007-1.

15. Gierse LC, Meene A, Schultz D, Schwaiger T, Schröder C, Mücke P, Zühlke D, Hinzke T, Wang H, Methling K. et al. Influenza a H1N1 induced disturbance of the respiratory and fecal microbiome of German landrace pigs - a multi-omics characterization. Microbiol Spectr. 2021;9(2):e00182-21. doi:10.1128/Spectrum.00182-21.

16. Sencio V, Gallerand A, Machado MG, Deruyter L, Heumel S, Soulard D, Barthelemy J, Cuinat C, Vieira AT, Barthelemy A. et al. Influenza virus infection impairs the gut's barrier properties and favors secondary enteric bacterial infection through reduced

production of short-chain fatty acids. Infect Immun. 2021;89(9). doi:10.1128/IAI.00734-20.

17. Qin N, Zheng B, Yao J, Guo L, Zuo J, Wu L, Zhou J, Liu L, Guo J, Ni S. et al. Influence of H7N9 virus infection and associated treatment on human gut microbiota. Sci Rep. 2015;5(1):14771. doi:10.1038/srep14771.

18. Gu S, Chen Y, Wu Z, Chen Y, Gao H, Lv L, Guo F, Zhang X, Luo R, Huang C. et al. Alterations of the gut microbiota in patients with coronavirus disease 2019 or H1N1 influenza. Clin Infect Dis. 2020;71(10):2669-2678. doi:10.1093/cid/ciaa709.

19. Al Khatib HA, Mathew S, Smatti MK, Eltai NO, Pathan SA, Al Thani AA, Coyle PV, Al Maslamani MA, Yassine HM. Profiling of intestinal microbiota in patients infected with respiratory influenza a and B viruses. Pathogens. 2021;10(6):761. doi:10.3390/pathogens10060761.

20. Fuentes S, den Hartog G, Nanlohy NM, Wijnands L, Ferreira JA, Nicolaie MA, Pennings JLA, Jacobi R, de Wit J, van Beek J. et al. Associations of faecal microbiota with influenza-like illness in participants aged 60 years or older: an observational study. Lancet Healthy Longevi. 2021;2(1):e13-e23. doi:10.1016/S2666-7568(20)30034-9.

21. Tessler M, Neumann JS, Afshinnekoo E, Pineda M, Hersch R, Velho LFM, Segovia BT, Lansac-Toha FA, Lemke M, DeSalle R. et al. Large-scale differences in microbial biodiversity discovery between 16S amplicon and shotgun sequencing. Sci Rep. 2017;7(1):6589. doi:10.1038/s41598-017-06665-3.

22. Brumfield KD, Huq A, Colwell RR, Olds JL, Leddy MB, Gyarmati P. Microbial resolution of whole genome shotgun and 16S amplicon metagenomic sequencing using publicly available NEON data. PLoS One. 2020;15(2):e0228899. doi:10.1371/journal.pone.0228899.

23. Nayfach S, Pollard KS. Toward accurate and quantitative comparative metagenomics. Cell. 2016;166(5):1103-1116. doi:10.1016/j.cell.2016.08.007.

24. Cani PD, de Vos WM. Next-generation beneficial microbes: the case of akkermansia muciniphila. Front Microbiol. 2017;8:1765. doi:10.3389/fmicb.2017.01765.

25. Aramaki T, Blanc-Mathieu R, Endo H, Ohkubo K, Kanehisa M, Goto S, Ogata H, Valencia A. KofamKOALA: KEGG ortholog assignment based on profile HMM and adaptive score threshold. Bioinformatics. 2020;36(7):2251-2252. doi:10.1093/bioinformatics/btz859.

26. Trompette A, Gollwitzer ES, Pattaroni C, Lopez-Mejia IC, Riva E, Pernot J, Ubags N, Fajas L, Nicod LP, Marsland BJ. Dietary fiber confers protection against flu by shaping Ly6c+ patrolling monocyte hematopoiesis and CD8+ T cell metabolism. Immunity. 2018;48(5):992-1005.e8. doi:10.1016/j.immuni.2018.04.022.

27. Gowda D, Li Y, Gowda B, Ohno SG, Chiba M, H Hui S-P. Determination of short-chain fatty acids by N,N-dimethylethylenediamine derivatization combined with liquid chromatography/mass spectrometry
<figure><img src="image_78.png" /></figure>

and their implication in influenza virus infection. *Anal Bioanal Chem.* 2022;414(22):6419-6430. doi:10.1007/s00216-022-04217-x.

28. Zeisel SH, Warrier M. Trimethylamine N -oxide, the microbiome, and heart and kidney disease. *Annu Rev Nutr.* 2017;37:157-181. doi:10.1146/annurev-nutr-071816-064732.

29. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. *Proc Natl Acad Sci USA.* 2009;106:3698-3703. doi:10.1073/pnas.0812874106.

30. Long SL, Gahan CGM, Joyce SA. Interactions between gut bacteria and bile in health and disease. *Mol Aspects Med.* 2017;56:54-65. doi:10.1016/j.mam.2017.06.002.

31. Rios-Covian D, González S, Nogacka AM, Arboleya S, Salazar N, Gueimonde M, de Los Reyes-Gavilán CG. An overview on fecal branched short-chain fatty acids along human life and as related with body mass index: associated dietary and anthropometric factors. *Front Microbiol.* 2020;11:973. doi:10.3389/fmicb.2020.00973.

32. Jiang H, Chen C, Gao J. Extensive summary of the important roles of indole propionic acid, a gut microbial metabolite in host health and disease. *Nutrients.* 2022;15:151. doi:10.3390/nu15010151.

33. Zhang B, Jiang M, Zhao J, Song Y, Du W, Shi J. The mechanism underlying the influence of indole-3-propionic acid: a relevance to metabolic disorders. *Front Endocrinol.* 2022;13. doi:10.3389/fendo.2022.841703.

34. Zhou X, Wu X, Wu Y, Yang L, Shi E, Ding W, Chen L, Shi X, Feng X, Su C. et al. Indole-3-propionic acid, a gut microbiota metabolite, protects against the development of postoperative delirium. *Annals Of Surgery.* 2023. doi:10.1097/SLA.0000000000005886. *Publish Ahead of Print*.

35. Serger E, Luengo-Gutierrez L, Chadwick JS, Kong G, Zhou L, Crawford G, Danzi MC, Myridakis A, Brandis A, Bello AT. et al. The gut metabolite indole-3-propionate promotes nerve regeneration and repair. *Nature.* 2022;607(7919):585-592. doi:10.1038/s41586-022-04884-x.

36. Cani PD, Depommier C, Derrien M, Everard A, de Vos WM. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. *Nat Rev Gastroenterol Hepatol.* 2022;19(10):625-637. doi:10.1038/s41575-022-00631-9.

37. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. *Int J Syst Evol Microbiol.* 2004;54(5):1469-1476. doi:10.1099/ijs.0.02873-0.

38. Groves HT, Cuthbertson L, James P, Moffatt MF, Cox MJ, Tregoning JS. Respiratory disease following viral lung infection alters the murine gut microbiota. *Front Immunol.* 2018;9:182. doi:10.3389/fimmu.2018.00182.

39. Schwabkey ZI, Wiesnoski DH, Chang C-C, Tsai W-B, Pham D, Ahmed SS, Hayase T, Ortega Turrubiates MR, El-Himri RK, Sanchez CA. et al. Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment. *Sci Transl Med.* 2022;14 (671):eabo3445. doi:10.1126/scitranslmed.abo3445.

40. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM. et al. Cross-talk between akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. *Proc Natl Acad Sci USA.* 2013;110(22):9066-9071. doi:10.1073/pnas.1219451110.

41. Seregin SS, Golovchenko N, Schaf B, Chen J, Pudlo NA, Mitchell J, Baxter NT, Zhao L, Schloss PD, Martens EC. et al. NLRP6 protects Il10-/- mice from colitis by limiting colonization of akkermansia muciniphila. *Cell Rep.* 2017;19(4):733-745. doi:10.1016/j.celrep.2017.03.080.

42. Li X, Li L, Li Y, Zhou R, Li B, Gu X, Fu S, Jin B, Zuo X, Li Y. Complete genome sequencing of peyer's patches-derived lactobacillus taiwanensis CLG01, a potential probiotic with antibacterial and immunomodulatory activity. *BMC Microbiol.* 2021;21(1):68. doi:10.1186/s12866-021-02127-z.

43. Mu Q, Tavella VJ, Luo XM. Role of lactobacillus reuteri in human health and diseases. *Front Microbiol.* 2018;9:757. doi:10.3389/fmicb.2018.00757.

44. Szajewska H, Gyrczuk E, Horvath A. Lactobacillus reuteri DSM 17938 for the management of infantile colic in breastfed infants: a randomized, double-blind, placebo-controlled trial. *J Pediatr.* 2013;162 (2):257-262. doi:10.1016/j.jpeds.2012.08.004.

45. Cheng J, Laitila A, Ouwehand AC. Bifidobacterium animalis subsp. lactis HN019 effects on gut health: a review. *Front Nutr.* 2021;8:790561. doi:10.3389/fnut. 2021.790561.

46. Uusitupa H-M, Rasinkangas P, Lehtinen MJ, Mäkelä SM, Airaksinen K, Anglenius H, Ouwehand AC, Maukonen J. Bifidobacterium animalis subsp. lactis 420 for metabolic health: review of the research. *Nutrients.* 2020;12(4):892. doi:10.3390/nu12040892.

47. Haak BW, Littmann ER, Chaubard J-L, Pickard AJ, Fontana E, Adhi F, Gyaltshen Y, Ling L, Morjaria SM, Peled JU. et al. Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT. *Blood.* 2018;131:2978-2986. doi:10.1182/blood-2018-01-828996.

48. Moriyama M, Ichinohe T. High ambient temperature dampens adaptive immune responses to influenza A virus infection. *Proc Natl Acad Sci USA.* 2019;116:3118-3125. doi:10.1073/pnas.1815029116.

49. von Gerichten J, Lamprecht D, Opálka L, Soulard D, Marsching C, Pilz R, Sencio V, Herzer S, Galy B, Nordström V. et al. Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation. *J Lipid Res.* 2019;60:1892-1904. doi:10.1194/jlr.RA119000236.
<figure><img src="image_77.png" /></figure>

and their implication in influenza virus infection. *Anal Bioanal Chem.* 2022;414(22):6419-6430. doi:10.1007/s00216-022-04217-x.

28. Zeisel SH, Warrier M. Trimethylamine N -oxide, the microbiome, and heart and kidney disease. *Annu Rev Nutr.* 2017;37:157-181. doi:10.1146/annurev-nutr-071816-064732.

29. Wikoff WR, Anfora AT, Liu J, Schultz PG, Lesley SA, Peters EC, Siuzdak G. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. *Proc Natl Acad Sci USA.* 2009;106:3698-3703. doi:10.1073/pnas.0812874106.

30. Long SL, Gahan CGM, Joyce SA. Interactions between gut bacteria and bile in health and disease. *Mol Aspects Med.* 2017;56:54-65. doi:10.1016/j.mam.2017.06.002.

31. Rios-Covian D, González S, Nogacka AM, Arboleya S, Salazar N, Gueimonde M, de Los Reyes-Gavilán CG. An overview on fecal branched short-chain fatty acids along human life and as related with body mass index: associated dietary and anthropometric factors. *Front Microbiol.* 2020;11:973. doi:10.3389/fmicb.2020.00973.

32. Jiang H, Chen C, Gao J. Extensive summary of the important roles of indole propionic acid, a gut microbial metabolite in host health and disease. *Nutrients.* 2022;15:151. doi:10.3390/nu15010151.

33. Zhang B, Jiang M, Zhao J, Song Y, Du W, Shi J. The mechanism underlying the influence of indole-3-propionic acid: a relevance to metabolic disorders. *Front Endocrinol.* 2022;13. doi:10.3389/fendo.2022.841703.

34. Zhou X, Wu X, Wu Y, Yang L, Shi E, Ding W, Chen L, Shi X, Feng X, Su C. et al. Indole-3-propionic acid, a gut microbiota metabolite, protects against the development of postoperative delirium. *Annals Of Surgery.* 2023. doi:10.1097/SLA.0000000000005886. *Publish Ahead of Print*.

35. Serger E, Luengo-Gutierrez L, Chadwick JS, Kong G, Zhou L, Crawford G, Danzi MC, Myridakis A, Brandis A, Bello AT. et al. The gut metabolite indole-3-propionate promotes nerve regeneration and repair. *Nature.* 2022;607(7919):585-592. doi:10.1038/s41586-022-04884-x.

36. Cani PD, Depommier C, Derrien M, Everard A, de Vos WM. Akkermansia muciniphila: paradigm for next-generation beneficial microorganisms. *Nat Rev Gastroenterol Hepatol.* 2022;19(10):625-637. doi:10.1038/s41575-022-00631-9.

37. Derrien M, Vaughan EE, Plugge CM, de Vos WM. Akkermansia muciniphila gen. nov., sp. nov., a human intestinal mucin-degrading bacterium. *Int J Syst Evol Microbiol.* 2004;54(5):1469-1476. doi:10.1099/ijs.0.02873-0.

38. Groves HT, Cuthbertson L, James P, Moffatt MF, Cox MJ, Tregoning JS. Respiratory disease following viral lung infection alters the murine gut microbiota. *Front Immunol.* 2018;9:182. doi:10.3389/fimmu.2018.00182.

39. Schwabkey ZI, Wiesnoski DH, Chang C-C, Tsai W-B, Pham D, Ahmed SS, Hayase T, Ortega Turrubiates MR, El-Himri RK, Sanchez CA. et al. Diet-derived metabolites and mucus link the gut microbiome to fever after cytotoxic cancer treatment. *Sci Transl Med.* 2022;14 (671):eabo3445. doi:10.1126/scitranslmed.abo3445.

40. Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM. et al. Cross-talk between akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. *Proc Natl Acad Sci USA.* 2013;110(22):9066-9071. doi:10.1073/pnas.1219451110.

41. Seregin SS, Golovchenko N, Schaf B, Chen J, Pudlo NA, Mitchell J, Baxter NT, Zhao L, Schloss PD, Martens EC. et al. NLRP6 protects Il10-/- mice from colitis by limiting colonization of akkermansia muciniphila. *Cell Rep.* 2017;19(4):733-745. doi:10.1016/j.celrep.2017.03.080.

42. Li X, Li L, Li Y, Zhou R, Li B, Gu X, Fu S, Jin B, Zuo X, Li Y. Complete genome sequencing of peyer's patches-derived lactobacillus taiwanensis CLG01, a potential probiotic with antibacterial and immunomodulatory activity. *BMC Microbiol.* 2021;21(1):68. doi:10.1186/s12866-021-02127-z.

43. Mu Q, Tavella VJ, Luo XM. Role of lactobacillus reuteri in human health and diseases. *Front Microbiol.* 2018;9:757. doi:10.3389/fmicb.2018.00757.

44. Szajewska H, Gyrczuk E, Horvath A. Lactobacillus reuteri DSM 17938 for the management of infantile colic in breastfed infants: a randomized, double-blind, placebo-controlled trial. *J Pediatr.* 2013;162 (2):257-262. doi:10.1016/j.jpeds.2012.08.004.

45. Cheng J, Laitila A, Ouwehand AC. Bifidobacterium animalis subsp. lactis HN019 effects on gut health: a review. *Front Nutr.* 2021;8:790561. doi:10.3389/fnut. 2021.790561.

46. Uusitupa H-M, Rasinkangas P, Lehtinen MJ, Mäkelä SM, Airaksinen K, Anglenius H, Ouwehand AC, Maukonen J. Bifidobacterium animalis subsp. lactis 420 for metabolic health: review of the research. *Nutrients.* 2020;12(4):892. doi:10.3390/nu12040892.

47. Haak BW, Littmann ER, Chaubard J-L, Pickard AJ, Fontana E, Adhi F, Gyaltshen Y, Ling L, Morjaria SM, Peled JU. et al. Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT. *Blood.* 2018;131:2978-2986. doi:10.1182/blood-2018-01-828996.

48. Moriyama M, Ichinohe T. High ambient temperature dampens adaptive immune responses to influenza A virus infection. *Proc Natl Acad Sci USA.* 2019;116:3118-3125. doi:10.1073/pnas.1815029116.

49. von Gerichten J, Lamprecht D, Opálka L, Soulard D, Marsching C, Pilz R, Sencio V, Herzer S, Galy B, Nordström V. et al. Bacterial immunogenic α-galactosylceramide identified in the murine large intestine: dependency on diet and inflammation. *J Lipid Res.* 2019;60:1892-1904. doi:10.1194/jlr.RA119000236.
<figure><img src="image_79.png" /></figure>

50. Groves HT, Higham SL, Moffatt MF, Cox MJ, Tregoning JS, Bomberger JM. Respiratory viral infection alters the gut microbiota by inducing inappetence. mBio. 2020;11(1). doi:10.1128/mBio.03236-19.

51. Lamas B, Richard ML, Leducq V, Pham H-P, Michel M-L, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016;22(6):598-605. doi:10.1038/nm.4102.

52. Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao C-C, Patel B, Yan R, Blain M. et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016;22(6):586-597. doi:10.1038/nm.4106.

53. Uebanso T, Shimohata T, Mawatari K, Takahashi A. Functional roles of B-Vitamins in the gut and gut microbiome. Mol Nutr Food Res. 2020;64:2000426. doi:10.1002/mnfr.202000426.

54. Antunes KH, Fachi JL, de Paula R, da Silva EF, Pral LP, dos Santos AÁ, Dias GBM, Vargas JE, Puga R, Mayer FQ. et al. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. Nat Commun. 2019;10(1):. doi:10.1038/s41467-019-11152-6.

55. Antunes KH, Stein RT, Franceschina C, da Silva EF, de Freitas DN, Silveira J, Mocellin M, Leitão L, Fachi JL, Pral LP. et al. Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis. EBioMedicine. 2022;77:103891. doi:10.1016/j.ebiom. 2022.103891.

56. Brown JA, Sanidad KZ, Lucotti S, Lieber CM, Cox RM, Ananthanarayanan A, Basu S, Chen J, Shan M, Amir M. et al. Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection. Gut Microbes. 2022;14(1):2105609. doi:10.1080/19490976.2022.2105609.

57. Cervantes-Barragan L, Chai JN, Tianero MD, Di Luccia B, Ahern PP, Merriman J, Cortez VS, Caparon MG, Donia MS, Gilfillan S. et al. *Lactobacillus reuteri* induces gut intraepithelial CD4⁺ CD8αα⁺ T cells. Science. 2017;357(6353):806-810. doi:10.1126/science.aah5825.

58. Roager HM, Licht TR. Microbial tryptophan catabolites in health and disease. Nat Commun. 2018;9(1):3294. doi:10.1038/s41467-018-05470-4.

59. Chou R-H, Wu P-S, Wang S-C, Wu C-H, Lu S-F, Lien R-Y, Tsai Y-L, Lu Y-W, Kuo M-R, Guo J-Y. et al. Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients. J Intensive Care. 2021;9(1):65.doi:10.1186/ s40560-021-00581-5.

60. Zhang Y, Wang Y, Ke B, Du J. TMAO: how gut microbiota contributes to heart failure. Transl Res. 2021;228:109-125. doi:10.1016/j.trsl.2020.08.007.

61. Wawrzyniak M, Groeger D, Frei R, Ferstl R, Wawrzyniak P, Krawczyk K, Pugin B, Barcik W, Westermann P, Dreher A. et al. Spermidine and spermine exert protective effects within the lung. Pharmacology Res & Perspec. 2021;9(4). doi:10.1002/ prp2.837.

62. Jain V, Raina S, Gheware AP, Singh R, Rehman R, Negi V, Murray Stewart T, Mabalirajan U, Mishra AK, Casero RA. Jimplemented to analyze the mouse serum. et al. Reduction in polyamine catabolism leads to spermine-mediated airway epithelial injury and induces asthma features. Allergy. 2018;73(10):2033-2045. doi:10.1111/all. 13472.

63. Wang, S., Xiong, L., Ruan, Z., Gong, X., Luo, Y., Wu, C., Wang, Y., Shang, H., and Chen, J. Indole-3-propionic acid alleviates sepsis-associated acute liver injury by activating pregnane X receptor. Molecular Medicine. 2023;29(1):65. doi:10.1186/s10020-023-00658-x.

64. Fang H, Fang M, Wang Y, Zhang H, Li J, Chen J, Wu Q, He L, Xu J, Deng J. et al. Indole-3-propionic acid as a potential therapeutic agent for sepsis-induced gut microbiota disturbance. Microbiol Spectr. 2022;10(3): e00125-22. doi:10.1128/spectrum.00125-22.

65. Guijas C, Horton LE, Hoang L, Domingo-Almenara X, Billings EM, Ware BC, Sullivan B, Siuzdak G. Microbial metabolite 3-indolepropionic acid mediates immunosuppression. Metabolites. 2022;12(7):645. doi:10.3390/metabo12070645.

66. Nyström S, Govender M, Yap SH, Kamarulzaman A, Rajasuriar R, Larsson M. HIV-Infected individuals on ART with impaired immune recovery have altered plasma metabolite profiles. Open Forum Infect Dis. 2021;8(7):ofab288. doi:10.1093/ofid/ofab288.

67. Ayari A, Rosa-Calatrava M, Lancel S, Barthelemy J, Pizzorno A, Mayeuf-Louchart A, Baron M, Hot D, Deruyter L, Soulard D. et al. Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues. Commun Biol. 2020;3(1):237. doi:10.1038/s42003-020-0965-6.

68. Shinde T, Hansbro PM, Sohal SS, Dingle P, Eri R, Stanley R. Microbiota modulating nutritional approaches to countering the effects of viral respiratory infections including SARS-CoV-2 through promoting metabolic and immune fitness with probiotics and plant bioactives. Microorganisms. 2020;8(6):E921. doi:10.3390/microorganisms8060921.

69. Trottein F, Sokol H. Potential causes and consequences of gastrointestinal disorders during a SARS-CoV-2 infection. Cell Rep. 2020;32:107915. doi:10.1016/j.cel rep.2020.107915.

70. Du L, Qi R, Wang J, Liu Z, Wu Z. Indole-3-propionic acid, a functional metabolite of clostridium sporogenes, promotes muscle tissue development and reduces muscle cell inflammation. IJMS. 2021;22(22):12435. doi:10. 3390/ijms222212435.
<figure><img src="image_78.png" /></figure>

50. Groves HT, Higham SL, Moffatt MF, Cox MJ, Tregoning JS, Bomberger JM. Respiratory viral infection alters the gut microbiota by inducing inappetence. mBio. 2020;11(1). doi:10.1128/mBio.03236-19.

51. Lamas B, Richard ML, Leducq V, Pham H-P, Michel M-L, Da Costa G, Bridonneau C, Jegou S, Hoffmann TW, Natividad JM. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat Med. 2016;22(6):598-605. doi:10.1038/nm.4102.

52. Rothhammer V, Mascanfroni ID, Bunse L, Takenaka MC, Kenison JE, Mayo L, Chao C-C, Patel B, Yan R, Blain M. et al. Type I interferons and microbial metabolites of tryptophan modulate astrocyte activity and central nervous system inflammation via the aryl hydrocarbon receptor. Nat Med. 2016;22(6):586-597. doi:10.1038/nm.4106.

53. Uebanso T, Shimohata T, Mawatari K, Takahashi A. Functional roles of B-Vitamins in the gut and gut microbiome. Mol Nutr Food Res. 2020;64:2000426. doi:10.1002/mnfr.202000426.

54. Antunes KH, Fachi JL, de Paula R, da Silva EF, Pral LP, dos Santos AÁ, Dias GBM, Vargas JE, Puga R, Mayer FQ. et al. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. Nat Commun. 2019;10(1):. doi:10.1038/s41467-019-11152-6.

55. Antunes KH, Stein RT, Franceschina C, da Silva EF, de Freitas DN, Silveira J, Mocellin M, Leitão L, Fachi JL, Pral LP. et al. Short-chain fatty acid acetate triggers antiviral response mediated by RIG-I in cells from infants with respiratory syncytial virus bronchiolitis. EBioMedicine. 2022;77:103891. doi:10.1016/j.ebiom. 2022.103891.

56. Brown JA, Sanidad KZ, Lucotti S, Lieber CM, Cox RM, Ananthanarayanan A, Basu S, Chen J, Shan M, Amir M. et al. Gut microbiota-derived metabolites confer protection against SARS-CoV-2 infection. Gut Microbes. 2022;14(1):2105609. doi:10.1080/19490976.2022.2105609.

57. Cervantes-Barragan L, Chai JN, Tianero MD, Di Luccia B, Ahern PP, Merriman J, Cortez VS, Caparon MG, Donia MS, Gilfillan S. et al. *Lactobacillus reuteri* induces gut intraepithelial CD4⁺ CD8αα⁺ T cells. Science. 2017;357(6353):806-810. doi:10.1126/science.aah5825.

58. Roager HM, Licht TR. Microbial tryptophan catabolites in health and disease. Nat Commun. 2018;9(1):3294. doi:10.1038/s41467-018-05470-4.

59. Chou R-H, Wu P-S, Wang S-C, Wu C-H, Lu S-F, Lien R-Y, Tsai Y-L, Lu Y-W, Kuo M-R, Guo J-Y. et al. Paradox of trimethylamine-N-oxide, the impact of malnutrition on microbiota-derived metabolites and septic patients. J Intensive Care. 2021;9(1):65.doi:10.1186/ s40560-021-00581-5.

60. Zhang Y, Wang Y, Ke B, Du J. TMAO: how gut microbiota contributes to heart failure. Transl Res. 2021;228:109-125. doi:10.1016/j.trsl.2020.08.007.

61. Wawrzyniak M, Groeger D, Frei R, Ferstl R, Wawrzyniak P, Krawczyk K, Pugin B, Barcik W, Westermann P, Dreher A. et al. Spermidine and spermine exert protective effects within the lung. Pharmacology Res & Perspec. 2021;9(4). doi:10.1002/ prp2.837.

62. Jain V, Raina S, Gheware AP, Singh R, Rehman R, Negi V, Murray Stewart T, Mabalirajan U, Mishra AK, Casero RA. Jimplemented to analyze the mouse serum. et al. Reduction in polyamine catabolism leads to spermine-mediated airway epithelial injury and induces asthma features. Allergy. 2018;73(10):2033-2045. doi:10.1111/all. 13472.

63. Wang, S., Xiong, L., Ruan, Z., Gong, X., Luo, Y., Wu, C., Wang, Y., Shang, H., and Chen, J. Indole-3-propionic acid alleviates sepsis-associated acute liver injury by activating pregnane X receptor. Molecular Medicine. 2023;29(1):65. doi:10.1186/s10020-023-00658-x.

64. Fang H, Fang M, Wang Y, Zhang H, Li J, Chen J, Wu Q, He L, Xu J, Deng J. et al. Indole-3-propionic acid as a potential therapeutic agent for sepsis-induced gut microbiota disturbance. Microbiol Spectr. 2022;10(3): e00125-22. doi:10.1128/spectrum.00125-22.

65. Guijas C, Horton LE, Hoang L, Domingo-Almenara X, Billings EM, Ware BC, Sullivan B, Siuzdak G. Microbial metabolite 3-indolepropionic acid mediates immunosuppression. Metabolites. 2022;12(7):645. doi:10.3390/metabo12070645.

66. Nyström S, Govender M, Yap SH, Kamarulzaman A, Rajasuriar R, Larsson M. HIV-Infected individuals on ART with impaired immune recovery have altered plasma metabolite profiles. Open Forum Infect Dis. 2021;8(7):ofab288. doi:10.1093/ofid/ofab288.

67. Ayari A, Rosa-Calatrava M, Lancel S, Barthelemy J, Pizzorno A, Mayeuf-Louchart A, Baron M, Hot D, Deruyter L, Soulard D. et al. Influenza infection rewires energy metabolism and induces browning features in adipose cells and tissues. Commun Biol. 2020;3(1):237. doi:10.1038/s42003-020-0965-6.

68. Shinde T, Hansbro PM, Sohal SS, Dingle P, Eri R, Stanley R. Microbiota modulating nutritional approaches to countering the effects of viral respiratory infections including SARS-CoV-2 through promoting metabolic and immune fitness with probiotics and plant bioactives. Microorganisms. 2020;8(6):E921. doi:10.3390/microorganisms8060921.

69. Trottein F, Sokol H. Potential causes and consequences of gastrointestinal disorders during a SARS-CoV-2 infection. Cell Rep. 2020;32:107915. doi:10.1016/j.cel rep.2020.107915.

70. Du L, Qi R, Wang J, Liu Z, Wu Z. Indole-3-propionic acid, a functional metabolite of clostridium sporogenes, promotes muscle tissue development and reduces muscle cell inflammation. IJMS. 2021;22(22):12435. doi:10. 3390/ijms222212435.
<figure><img src="image_80.png" /></figure>

71. Barthelemy A, Ivanov S, Fontaine J, Soulard D, Bouabe H, Paget C, Faveeuw C, Trottein F. Influenza a virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection. Mucosal Immunol. 2017;10 (2):460-469. doi:10.1038/mi.2016.49.

72. Barthelemy A, Sencio V, Soulard D, Deruyter L, Faveeuw C, Le Goffic R, Trottein F, Bäumler AJ. Interleukin-22 immunotherapy during severe influenza enhances lung tissue integrity and reduces secondary bacterial systemic invasion. Infect Immun. 2018;86(7): e00706-17. doi:10.1128/IAI.00706-17.

73. Xue H, Chen X, Yu C, Deng Y, Zhang Y, Chen S, Chen X, Chen K, Yang Y, Ling W. Gut microbially produced indole-3-propionic acid inhibits atherosclerosis by promoting reverse cholesterol transport and its deficiency is causally related to atherosclerotic cardiovascular disease. Circ Res. 2022;131(5):404-420. doi:10.1161/CIRCRESAHA.122.321253.

74. Chen X, Liu S, Goraya MU, Maarouf M, Huang S, Chen J-L. Host Immune Response to Influenza A Virus Infection. Front Immunol. 2018;9:320. doi:10.3389/fimmu.2018.00320.

75. Langmead B, Salzberg SL. Fast gapped-read alignment with bowtie 2. Nat Methods. 2012;9(4):357-359. doi:10.1038/nmeth.1923.

76. Clarke KR. Non-parametric multivariate analyses of changes in community structure. Austral Ecol. 1993;18 (1):117-143. doi:10.1111/j.1442-9993.1993.tb00438.x.

77. Milanese A, Mende DR, Paoli L, Salazar G, Ruscheweyh H-J, Cuenca M, Hingamp P, Alves R, Costea PI, Coelho LP. et al. Microbial abundance, activity and population genomic profiling with mOtus2. Nat Commun. 2019;10(1):1014. doi:10.1038/s41467-019-08844-4.

78. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6): R60. doi:10.1186/gb-2011-12-6-r60.

79. Lesker TR, Durairaj AC, Gálvez EJC, Lagkouvardos I, Baines JF, Clavel T, Sczyrba A, McHardy AC, Strowig T. An integrated metagenome catalog reveals new insights into the murine gut microbiome. Cell Reports. 2020;30(9):2909-2922.e6. doi:10.1016/j.cel rep.2020.02.036.

80. Pereira MB, Wallroth M, Jonsson V, Kristiansson E. Comparison of normalization methods for the analysis of metagenomic gene abundance data. BMC Genomics. 2018;19(1):274. doi:10.1186/s12864-018-4637-6.

81. Morton JT, Marotz C, Washburne A, Silverman J, Zaramela LS, Edlund A, Zengler K, Knight R. Establishing microbial composition measurement standards with reference frames. Nat Commun. 2019;10 (1):2719. doi:10.1038/s41467-019-10656-5.

82. Team TPD. 2022. pandas-dev/pandas: Pandas. Version v1.5.1 (Zenodo). doi:10.5281/ZENODO.3509134.

83. McKinney W. Data structures for statistical computing in python. In. 2010:56-61. doi:10.25080/Majora-92bf1922-00a.

84. Ghazi AR, Sucipto K, Rahnavard A, Franzosa EA, McIver LJ, Lloyd-Price J, Schwager E, Weingart G, Moon YS, Morgan XC. et al. High-sensitivity pattern discovery in large, paired multiomic datasets. Bioinformatics. 2022;38(Supplement_1):i378-i385. doi:10.1093/bioinformatics/btac232.
<figure><img src="image_79.png" /></figure>

71. Barthelemy A, Ivanov S, Fontaine J, Soulard D, Bouabe H, Paget C, Faveeuw C, Trottein F. Influenza a virus-induced release of interleukin-10 inhibits the anti-microbial activities of invariant natural killer T cells during invasive pneumococcal superinfection. Mucosal Immunol. 2017;10 (2):460-469. doi:10.1038/mi.2016.49.

72. Barthelemy A, Sencio V, Soulard D, Deruyter L, Faveeuw C, Le Goffic R, Trottein F, Bäumler AJ. Interleukin-22 immunotherapy during severe influenza enhances lung tissue integrity and reduces secondary bacterial systemic invasion. Infect Immun. 2018;86(7): e00706-17. doi:10.1128/IAI.00706-17.

73. Xue H, Chen X, Yu C, Deng Y, Zhang Y, Chen S, Chen X, Chen K, Yang Y, Ling W. Gut microbially produced indole-3-propionic acid inhibits atherosclerosis by promoting reverse cholesterol transport and its deficiency is causally related to atherosclerotic cardiovascular disease. Circ Res. 2022;131(5):404-420. doi:10.1161/CIRCRESAHA.122.321253.

74. Chen X, Liu S, Goraya MU, Maarouf M, Huang S, Chen J-L. Host Immune Response to Influenza A Virus Infection. Front Immunol. 2018;9:320. doi:10.3389/fimmu.2018.00320.

75. Langmead B, Salzberg SL. Fast gapped-read alignment with bowtie 2. Nat Methods. 2012;9(4):357-359. doi:10.1038/nmeth.1923.

76. Clarke KR. Non-parametric multivariate analyses of changes in community structure. Austral Ecol. 1993;18 (1):117-143. doi:10.1111/j.1442-9993.1993.tb00438.x.

77. Milanese A, Mende DR, Paoli L, Salazar G, Ruscheweyh H-J, Cuenca M, Hingamp P, Alves R, Costea PI, Coelho LP. et al. Microbial abundance, activity and population genomic profiling with mOtus2. Nat Commun. 2019;10(1):1014. doi:10.1038/s41467-019-08844-4.

78. Segata N, Izard J, Waldron L, Gevers D, Miropolsky L, Garrett WS, Huttenhower C. Metagenomic biomarker discovery and explanation. Genome Biol. 2011;12(6): R60. doi:10.1186/gb-2011-12-6-r60.

79. Lesker TR, Durairaj AC, Gálvez EJC, Lagkouvardos I, Baines JF, Clavel T, Sczyrba A, McHardy AC, Strowig T. An integrated metagenome catalog reveals new insights into the murine gut microbiome. Cell Reports. 2020;30(9):2909-2922.e6. doi:10.1016/j.cel rep.2020.02.036.

80. Pereira MB, Wallroth M, Jonsson V, Kristiansson E. Comparison of normalization methods for the analysis of metagenomic gene abundance data. BMC Genomics. 2018;19(1):274. doi:10.1186/s12864-018-4637-6.

81. Morton JT, Marotz C, Washburne A, Silverman J, Zaramela LS, Edlund A, Zengler K, Knight R. Establishing microbial composition measurement standards with reference frames. Nat Commun. 2019;10 (1):2719. doi:10.1038/s41467-019-10656-5.

82. Team TPD. 2022. pandas-dev/pandas: Pandas. Version v1.5.1 (Zenodo). doi:10.5281/ZENODO.3509134.

83. McKinney W. Data structures for statistical computing in python. In. 2010:56-61. doi:10.25080/Majora-92bf1922-00a.

84. Ghazi AR, Sucipto K, Rahnavard A, Franzosa EA, McIver LJ, Lloyd-Price J, Schwager E, Weingart G, Moon YS, Morgan XC. et al. High-sensitivity pattern discovery in large, paired multiomic datasets. Bioinformatics. 2022;38(Supplement_1):i378-i385. doi:10.1093/bioinformatics/btac232.