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Healthy Human Gastrointestinal Microbiome: Composition and Function After a Decade of Exploration

Digestive Diseases and Sciences volume 65, pages 695–705 (2020)Cite this article

Abstract

The human gastrointestinal (GI) tract contains communities of microbes (bacteria, fungi, viruses) that vary by anatomic location and impact human health. Microbial communities differ in composition based on age, diet, and location in the gastrointestinal tract. Differences in microbial composition have been associated with chronic disease states. In terms of function, microbial metabolites provide key signals that help maintain healthy human physiology. Alterations of the healthy gastrointestinal microbiome have been linked to the development of various disease states including inflammatory bowel disease, diabetes, and colorectal cancer. While the definition of a healthy GI microbiome cannot be precisely identified, features of a healthy gut microbiome include relatively greater biodiversity and relative abundances of specific phyla and genera. Microbes with desirable functional profiles for the human host have been identified, in addition to specific metabolic features of the microbiome. This article reviews the composition and function of the healthy human GI microbiome, including the relative abundances of different bacterial taxa and the specific metabolic pathways and classes of microbial metabolites contributing to human health and disease prevention.

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Fig. 1
Fig. 2

Abbreviations

GI:

Gastrointestinal

HMP:

Human Microbiome Project

MetaHIT:

Metagenomics of the Human Intestinal Tract

IBD:

Inflammatory bowel disease

References

  1. Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. 2016;14:e1002533.

    PubMed  PubMed Central  Google Scholar 

  2. Bull MJ, Plummer NT. Part 1: The human gut microbiome in health and disease. Integr Med. 2014;13:17–22.

    Google Scholar 

  3. Rath CM, Dorrestein PC. The bacterial chemical repertoire mediates metabolic exchange within gut microbiomes. Curr Opin Microbiol. 2012;15:147–154.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI. The human microbiome project. Nature. 2007;449:804–810.

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Ehrlich SD. MetaHIT: the European Union Project on metagenomics of the human intestinal tract. In: Nelson KE, ed. Metagenomics of the Human Body, City. Springer: New York; 2011:307–316.

    Google Scholar 

  6. Arnold JW, Roach J, Azcarate-Peril MA. Emerging technologies for gut microbiome research. Trends Microbiol. 2016;24:887–901.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Flint HJ. The impact of nutrition on the human microbiome. Nutr Rev. 2012;70:S10–S13.

    PubMed  PubMed Central  Google Scholar 

  8. Marchesi JR, Dutilh BE, Hall N, et al. Towards the human colorectal cancer microbiome. PLoS ONE. 2011;6:e20447.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Halfvarson J, Brislawn CJ, Lamendella R, et al. Dynamics of the human gut microbiome in inflammatory bowel disease. Nat Microbiol. 2017;2:17004.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Chong PP, Chin VK, Looi CY, Wong WF, Madhavan P, Yong VC. The microbiome and irritable bowel syndrome: a review on the pathophysiology. Curr Res Future Ther Front Microbiol. 2019;10:1136.

    Google Scholar 

  11. Chumpitazi BP, Cope JL, Hollister EB, et al. Randomised clinical trial: gut microbiome biomarkers are associated with clinical response to a low FODMAP diet in children with the irritable bowel syndrome. Aliment Pharmacol Ther. 2015;42:418–427.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Sharma S, Tripathi P. Gut microbiome and type 2 diabetes: where we are and where to go? J Nutrit Biochem. 2019;63:101–108.

    CAS  Google Scholar 

  13. Hollister EB, Riehle K, Luna RA, et al. Structure and function of the healthy pre-adolescent pediatric gut microbiome. Microbiome. 2015;3:36.

    PubMed  PubMed Central  Google Scholar 

  14. Marcobal A, Sonnenburg JL. Human milk oligosaccharide consumption by intestinal microbiota. Clin Microbiol Infect. 2012;18:12–15.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Matamoros S, Gras-Leguen C, Le Vacon F, Potel G, de La Cochetiere MF. Development of intestinal microbiota in infants and its impact on health. Trends Microbiol. 2013;21:167–173.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Aagaard K, Petrosino J, Keitel W, et al. The Human Microbiome Project strategy for comprehensive sampling of the human microbiome and why it matters. FASEB J. 2013;27:1012–1022.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. McBurney MI, Davis C, Fraser CM, et al. Establishing what constitutes a healthy human gut microbiome: state of the science, regulatory considerations, and future directions. J Nutr. 2019;149:1882–1895.

    PubMed  PubMed Central  Google Scholar 

  18. Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016;8:51.

    PubMed  PubMed Central  Google Scholar 

  19. Lloyd-Price J, Mahurkar A, Rahnavard G, et al. Strains, functions and dynamics in the expanded Human Microbiome Project. Nature. 2017;550:61–66.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Dobbler PT, Procianoy RS, Mai V, et al. Low microbial diversity and abnormal microbial succession is associated with necrotizing enterocolitis in preterm infants. Front Microbiol. 2017;8:2243.

    PubMed  PubMed Central  Google Scholar 

  21. Ni J, Wu GD, Albenberg L, Tomov VT. Gut microbiota and IBD: causation or correlation? Nat Rev Gastroenterol Hepatol. 2017;14:573–584.

    PubMed  PubMed Central  Google Scholar 

  22. Ding RX, Goh WR, Wu RN, et al. Revisit gut microbiota and its impact on human health and disease. J Food Drug Anal. 2019;27:623–631.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Fragiadakis GK, Smits SA, Sonnenburg ED, et al. Links between environment, diet, and the hunter-gatherer microbiome. Gut Microbes. 2019;10:216–227.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Dethlefsen L, Huse S, Sogin ML, Relman DA. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biol. 2008;6:e280.

    PubMed  PubMed Central  Google Scholar 

  25. Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–214.

    Google Scholar 

  26. Tuddenham S, Sears CL. The intestinal microbiome and health. Curr Opin Infect Dis. 2015;28:464–470.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Martinez I, Maldonado-Gomez MX, Gomes-Neto JC, et al. Experimental evaluation of the importance of colonization history in early-life gut microbiota assembly. Elife. 2018;7:e36521.

    PubMed  PubMed Central  Google Scholar 

  28. Rothschild D, Weissbrod O, Barkan E, et al. Environment dominates over host genetics in shaping human gut microbiota. Nature. 2018;555:210–215.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Backhed F, Fraser CM, Ringel Y, et al. Defining a healthy human gut microbiome: current concepts, future directions, and clinical applications. Cell Host Microbe. 2012;12:611–622.

    PubMed  PubMed Central  Google Scholar 

  30. Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol. 1996;4:430–435.

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Dewhirst FE, Chen T, Izard J, et al. The human oral microbiome. J Bacteriol. 2010;192:5002–5017.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Vasapolli R, Schutte K, Schulz C et al. Analysis of transcriptionally active bacteria throughout the gastrointestinal tract of healthy individuals. Gastroenterology. 2019.

  33. Li K, Bihan M, Yooseph S, Methé BA. Analyses of the microbial diversity across the human microbiome. PloS One. 2012;7:e32118.

    CAS  PubMed  PubMed Central  Google Scholar 

  34. May M, Abrams JA. Emerging insights into the esophageal microbiome. Curr Treat Options Gastroenterol. 2018;16:72–85.

    PubMed  PubMed Central  Google Scholar 

  35. Hillman ET, Lu H, Yao T, Nakatsu CH. Microbial ecology along the gastrointestinal tract. Microbes Environ. 2017;32:300–313.

    PubMed  PubMed Central  Google Scholar 

  36. Deshpande NP, Riordan SM, Castano-Rodriguez N, Wilkins MR, Kaakoush NO. Signatures within the esophageal microbiome are associated with host genetics, age, and disease. Microbiome. 2018;6:227.

    PubMed  PubMed Central  Google Scholar 

  37. Bik EM, Eckburg PB, Gill SR, et al. Molecular analysis of the bacterial microbiota in the human stomach. Proc Natl Acad Sci US A. 2006;103:732–737.

    CAS  Google Scholar 

  38. Dash NR, Khoder G, Nada AM, Al Bataineh MT. Exploring the impact of Helicobacter pylori on gut microbiome composition. PloS One. 2019;14:e0218274.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Gu S, Chen D, Zhang JN, et al. Bacterial community mapping of the mouse gastrointestinal tract. PloS one. 2013;8:e74957.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Sundin OH, Mendoza-Ladd A, Zeng M, et al. The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon. BMC Microbiol. 2017;17:160.

    PubMed  PubMed Central  Google Scholar 

  41. Hayashi H, Takahashi R, Nishi T, Sakamoto M, Benno Y. Molecular analysis of jejunal, ileal, caecal and recto-sigmoidal human colonic microbiota using 16S rRNA gene libraries and terminal restriction fragment length polymorphism. J Med Microbiol. 2005;54:1093–1101.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Scheithauer TP, Dallinga-Thie GM, de Vos WM, Nieuwdorp M, van Raalte DH. Causality of small and large intestinal microbiota in weight regulation and insulin resistance. Mol Metab. 2016;5:759–770.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Johansson ME, Larsson JM, Hansson GC. The two mucus layers of colon are organized by the MUC2 mucin, whereas the outer layer is a legislator of host-microbial interactions. Proc Natl Acad Sci USA. 2011;108:4659–4665.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Tropini C, Earle KA, Huang KC, Sonnenburg JL. The gut microbiome: connecting spatial organization to function. Cell Host Microbe. 2017;21:433–442.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Berry D, Stecher B, Schintlmeister A, et al. Host-compound foraging by intestinal microbiota revealed by single-cell stable isotope probing. Proc Natl Acad Sci USA. 2013;110:4720–4725.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Crost EH, Tailford LE, Monestier M, et al. The mucin-degradation strategy of Ruminococcus gnavus: the importance of intramolecular trans-sialidases. Gut Microbes. 2016;7:302–312.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Yasuda K, Oh K, Ren B, et al. Biogeography of the intestinal mucosal and lumenal microbiome in the rhesus macaque. Cell Host Microbe. 2015;17:385–391.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Albenberg L, Esipova TV, Judge CP, et al. Correlation between intraluminal oxygen gradient and radial partitioning of intestinal microbiota. Gastroenterology. 2014;147:e1058.

    Google Scholar 

  49. Faith JJ, Guruge JL, Charbonneau M, et al. The long-term stability of the human gut microbiota. Science. 2013;341:1237439.

    PubMed  PubMed Central  Google Scholar 

  50. Rajilic-Stojanovic M, Heilig HG, Tims S, Zoetendal EG, de Vos WM. Long-term monitoring of the human intestinal microbiota composition. Environ Microbiol. 2012.

  51. Hamady M, Knight R. Microbial community profiling for human microbiome projects: tools, techniques, and challenges. Genome Res. 2009;19:1141–1152.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Zoetendal EG, Rajilic-Stojanovic M, de Vos WM. High-throughput diversity and functionality analysis of the gastrointestinal tract microbiota. Gut. 2008;57:1605–1615.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464:59–65.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Kolmeder CA, de Been M, Nikkila J, et al. Comparative metaproteomics and diversity analysis of human intestinal microbiota testifies for its temporal stability and expression of core functions. PloS One. 2012;7:e29913.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Shetty SA, Hugenholtz F, Lahti L, Smidt H, de Vos WM. Intestinal microbiome landscaping: insight in community assemblage and implications for microbial modulation strategies. FEMS Microbiol Rev. 2017;41:182–199.

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Hall AB, Tolonen AC, Xavier RJ. Human genetic variation and the gut microbiome in disease. Nat Rev Genet. 2017;18:690–699.

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Png CW, Linden SK, Gilshenan KS, et al. Mucolytic bacteria with increased prevalence in IBD mucosa augment in vitro utilization of mucin by other bacteria. Am J Gastroenterol. 2010;105:2420–2428.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Li YH, Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel). 2012;12:2519–2538.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol. 2001;55:165–199.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319–346.

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Parsek MR, Greenberg EP. Sociomicrobiology: the connections between quorum sensing and biofilms. Trends Microbiol. 2005;13:27–33.

    CAS  PubMed  PubMed Central  Google Scholar 

  62. Thompson JA, Oliveira RA, Xavier KB. Chemical conversations in the gut microbiota. Gut Microbes. 2016;7:163–170.

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Cvitkovitch DG, Li YH, Ellen RP. Quorum sensing and biofilm formation in Streptococcal infections. J Clin Invest. 2003;112:1626–1632.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Thompson JA, Oliveira RA, Djukovic A, Ubeda C, Xavier KB. Manipulation of the quorum sensing signal AI-2 affects the antibiotic-treated gut microbiota. Cell Rep. 2015;10:1861–1871.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Dobson A, Cotter PD, Ross RP, Hill C. Bacteriocin production: a probiotic trait? Appl Environ Microbiol. 2012;78:1–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Ventura M, Turroni F, Motherway MO, MacSharry J, van Sinderen D. Host-microbe interactions that facilitate gut colonization by commensal bifidobacteria. Trends Microbiol. 2012;20:467–476.

    CAS  Google Scholar 

  67. Chen Y, Ludescher RD, Montville TJ. Electrostatic interactions, but not the YGNGV consensus motif, govern the binding of pediocin PA-1 and its fragments to phospholipid vesicles. Appl Environ Microbiol. 1997;63:4770–4777.

    CAS  PubMed  PubMed Central  Google Scholar 

  68. Gut IM, Blanke SR, van der Donk WA. Mechanism of inhibition of Bacillus anthracis spore outgrowth by the lantibiotic nisin. ACS Chem Biol. 2011;6:744–752.

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Li J, Aroutcheva AA, Faro S, Chikindas ML. Mode of action of lactocin 160, a bacteriocin from vaginal Lactobacillus rhamnosus. Infect Dis Obstet Gynecol. 2005;13:135–140.

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Devi M, Rebecca LJ, Sumathy S. Bactericidal activity of the lactic acid bacteria Lactobacillus delbreukii. J Chem Pharm Res. 2013;5:176–180.

    Google Scholar 

  71. Alakomi HL, Skytta E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM. Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol. 2000;66:2001–2005.

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Kong Y-J, Park B-K, Oh D-H. Antimicrobial activity of quercus mongolica leaf ethanol extract and organic acids against food-borne microorganisms. Korean J Food Sci Technol. 2001;33:178–183.

    Google Scholar 

  73. Ray B, Sandine WE. Acetic, Propionic, and Lactic Acids of Starter Culture Bacteria as Biopreservatives. London: CRC Press; 1992.

    Google Scholar 

  74. Mani-Lópeza E, Garcíaa HS, López-Malo A. Organic acids as antimicrobials to control Salmonella in meat and poultry products. Food Res Int. 2012;45:713–721.

    Google Scholar 

  75. Atassi F, Servin AL. Individual and co-operative roles of lactic acid and hydrogen peroxide in the killing activity of enteric strain Lactobacillus johnsonii NCC933 and vaginal strain Lactobacillus gasseri KS120.1 against enteric, uropathogenic and vaginosis-associated pathogens. FEMS Microbiol Lett. 2010;304:29–38.

    CAS  PubMed  PubMed Central  Google Scholar 

  76. Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003;67:593–656.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Ananthaswamy HN, Eisenstark A. Repair of hydrogen peroxide-induced single-strand breaks in Escherichia coli deoxyribonucleic acid. J Bacteriol. 1977;130:187–191.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Freese EB, Gerson J, Taber H, Rhaese HJ, Freese E. Inactivating DNA alterations induced by peroxides and peroxide-producing agents. Mutat Res. 1967;4:517–531.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Di Mascio P, Wefers H, Do-Thi HP, Lafleur MV, Sies H. Singlet molecular oxygen causes loss of biological activity in plasmid and bacteriophage DNA and induces single-strand breaks. Biochim Biophys Acta. 1989;1007:151–157.

    PubMed  PubMed Central  Google Scholar 

  80. Florence TM. The production of hydroxyl radical from the reaction between hydrogen peroxide and NADH. J Inorg Biochem. 1986;28:33–37.

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Watanabe T, Nishio H, Tanigawa T, et al. Probiotic Lactobacillus casei strain Shirota prevents indomethacin-induced small intestinal injury: involvement of lactic acid. Am J Physiol Gastrointest Liver Physiol. 2009;297:G506–G513.

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Vollenweider S, Grassi G, Konig I, Puhan Z. Purification and structural characterization of 3-hydroxypropionaldehyde and its derivatives. J Agric Food Chem. 2003;51:3287–3293.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Walter J, Britton RA, Roos S. Host-microbial symbiosis in the vertebrate gastrointestinal tract and the Lactobacillus reuteri paradigm. Proc Natl Acad Sci USA. 2011;108(Suppl 1):4645–4652.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Cleusix V, Lacroix C, Vollenweider S, Duboux M, Le Blay G. Inhibitory activity spectrum of reuterin produced by Lactobacillus reuteri against intestinal bacteria. BMC Microbiol. 2007;7:101.

    PubMed  PubMed Central  Google Scholar 

  85. Spinler JK, Auchtung J, Brown A et al. Next-generation probiotics targeting clostridium difficile through precursor-directed antimicrobial biosynthesis. Infect Immun. 2017;85.

  86. Spinler JK, Taweechotipatr M, Rognerud CL, Ou CN, Tumwasorn S, Versalovic J. Human-derived probiotic Lactobacillus reuteri demonstrate antimicrobial activities targeting diverse enteric bacterial pathogens. Anaerobe. 2008;14:166–171.

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Axelsson LT, Chung TC, Dobrogosz WJ, Lindgren SE. Production of a broad spectrum antimicrobial substance by Lactobacillus reuteri. Microbial Ecol Health Dis. 1989;2:131–136.

    Google Scholar 

  88. Talarico TL, Axelsson LT, Novotny J, Fiuzat M, Dobrogosz WJ. Utilization of glycerol as a hydrogen acceptor by Lactobacillus reuteri: purification of 1,3-propanediol: NAD oxidoreductase. Appl Environ Microbiol. 1990;56:943–948.

    CAS  PubMed  PubMed Central  Google Scholar 

  89. Das NK, Schwartz AJ, Barthel Get al. Microbial metabolite signaling is required for systemic iron homeostasis. Cell Metab. 2019.

  90. Manoppo J, Tasiringan H, Wahani A, Umboh A, Mantik M. The role of Lactobacillus reuteri DSM 17938 for the absorption of iron preparations in children with iron deficiency anemia. Korean J Pediatr. 2019;62:173–178.

    PubMed  PubMed Central  Google Scholar 

  91. Rodwell AW. The histidine decarboxylase of a species of Lactobacillus; apparent dispensability of pyridoxal phosphate as coenzyme. J Gen Microbiol. 1953;8:233–237.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Rossi F, Gardini F, Rizzotti L, La Gioia F, Tabanelli G, Torriani S. Quantitative analysis of histidine decarboxylase gene (hdcA) transcription and histamine production by Streptococcus thermophilus PRI60 under conditions relevant to cheese making. Appl Environ Microbiol. 2011;77:2817–2822.

    CAS  PubMed  PubMed Central  Google Scholar 

  93. Hemarajata P, Gao C, Pflughoeft KJ, et al. Lactobacillus reuteri-specific immunoregulatory gene rsiR modulates histamine production and immunomodulation by Lactobacillus reuteri. J Bacteriol. 2013;195:5567–5576.

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Thomas CM, Hong T, van Pijkeren JP, et al. Histamine derived from probiotic Lactobacillus reuteri suppresses TNF via modulation of PKA and ERK signaling. PloS one. 2012;7:e31951.

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Pessione E, Mazzoli R, Giuffrida MG, et al. A proteomic approach to studying biogenic amine producing lactic acid bacteria. Proteomics. 2005;5:687–698.

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Lucas PM, Claisse O, Lonvaud-Funel A. High frequency of histamine-producing bacteria in the enological environment and instability of the histidine decarboxylase production phenotype. Appl Environ Microbiol. 2008;74:811–817.

    CAS  PubMed  PubMed Central  Google Scholar 

  97. Izquierdo Canas PM, Gomez Alonso S, Ruiz Perez P, Sesena Prieto S, Garcia Romero E, Palop Herreros ML. Biogenic amine production by Oenococcus oeni isolates from malolactic fermentation of Tempranillo wine. J Food Prot. 2009;72:907–910.

    CAS  PubMed  PubMed Central  Google Scholar 

  98. Komatsuzaki N, Shima J, Kawamotoa S, Momosed H, Kimurab T. Production of y-aminobutyric acid (GABA) by Lactobacillus paracasei isolated from traditional fermented foods. Food Microbiol. 2005;22:497–504.

    CAS  Google Scholar 

  99. Siragusa S, De Angelis M, Di Cagno R, Rizzello CG, Coda R, Gobbetti M. Synthesis of gamma-aminobutyric acid by lactic acid bacteria isolated from a variety of Italian cheeses. Appl Environ Microbiol. 2007;73:7283–7290.

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Pokusaeva K, Johnson C, Luk B, et al. GABA-producing Bifidobacterium dentium modulates visceral sensitivity in the intestine. Neurogastroenterol Motil. 2016;. https://doi.org/10.1111/nmo.12904.

    Article  PubMed  PubMed Central  Google Scholar 

  101. Cohen SS. A Guide to the Polyamines. Oxford: Oxford University Press; 1997.

    Google Scholar 

  102. Shah P, Swiatlo E. A multifaceted role for polyamines in bacterial pathogens. Mol Microbiol. 2008;68:4–16.

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Noack J, Kleessen B, Proll J, Dongowski G, Blaut M. Dietary guar gum and pectin stimulate intestinal microbial polyamine synthesis in rats. J Nutr. 1998;128:1385–1391.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Aragozzini F, Ferrari A, Pacini N, Gualandris R. Indole-3-lactic acid as a tryptophan metabolite produced by Bifidobacterium spp. Appl Environ Microbiol. 1979;38:544–546.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Keszthelyi D, Troost FJ, Masclee AA. Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function. Neurogastroenterol Motil. 2009;21:1239–1249.

    CAS  PubMed  PubMed Central  Google Scholar 

  106. Smith EA, Macfarlane GT. Formation of phenolic and indolic compounds by anaerobic bacteria in the human large intestine. Microb Ecol. 1997;33:180–188.

    CAS  PubMed  PubMed Central  Google Scholar 

  107. Bansal T, Alaniz RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci USA. 2010;107:228–233.

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Ruhlmann A, Kukla D, Schwager P, Bartels K, Huber R. Structure of the complex formed by bovine trypsin and bovine pancreatic trypsin inhibitor. Crystal structure determination and stereochemistry of the contact region. J Mol Biol. 1973;77:417–436.

    CAS  PubMed  PubMed Central  Google Scholar 

  109. Potempa J, Korzus E, Travis J. The serpin superfamily of proteinase inhibitors: structure, function, and regulation. J Biol Chem. 1994;269:15957–15960.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. Turroni F, Foroni E, Motherway MOC, et al. Characterization of the serpin-encoding gene of Bifidobacterium breve 210B. Appl Environ Microbiol. 2010;76:3206–3219.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Schell MA, Karmirantzou M, Snel B, et al. The genome sequence of Bifidobacterium longum reflects its adaptation to the human gastrointestinal tract. Proc Natl Acad Sci USA. 2002;99:14422–14427.

    CAS  PubMed  PubMed Central  Google Scholar 

  112. Ivanov D, Emonet C, Foata F, et al. A serpin from the gut bacterium Bifidobacterium longum inhibits eukaryotic elastase-like serine proteases. J Biol Chem. 2006;281:17246–17252.

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Haandrikman AJ, Kok J, Laan H, et al. Identification of a gene required for maturation of an extracellular lactococcal serine proteinase. J Bacteriol. 1989;171:2789–2794.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Haandrikman AJ, Kok J, Venema G. Lactococcal proteinase maturation protein PrtM is a lipoprotein. J Bacteriol. 1991;173:4517–4525.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Holck A, Axelsson L, Birkeland SE, Aukrust T, Blom H. Purification and amino acid sequence of sakacin A, a bacteriocin from Lactobacillus sake Lb706. J Gen Microbiol. 1992;138:2715–2720.

    CAS  PubMed  PubMed Central  Google Scholar 

  116. Hoermannsperger G, Clavel T, Hoffmann M, et al. Post-translational inhibition of IP-10 secretion in IEC by probiotic bacteria: impact on chronic inflammation. PloS one. 2009;4:e4365.

    PubMed  PubMed Central  Google Scholar 

  117. von Schillde MA, Hormannsperger G, Weiher M, et al. Lactocepin secreted by Lactobacillus exerts anti-inflammatory effects by selectively degrading proinflammatory chemokines. Cell Host Microbe. 2012;11:387–396.

    Google Scholar 

  118. Furusawa Y, Obata Y, Fukuda S, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504:446–450.

    CAS  PubMed  PubMed Central  Google Scholar 

  119. Singh N, Gurav A, Sivaprakasam S, et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity. 2014;40:128–139.

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Belenguer A, Duncan SH, Calder AG, et al. Two routes of metabolic cross-feeding between Bifidobacterium adolescentis and butyrate-producing anaerobes from the human gut. Appl Environ Microbiol. 2006;72:3593–3599.

    CAS  PubMed  PubMed Central  Google Scholar 

  121. Louis P, Duncan SH, McCrae SI, Millar J, Jackson MS, Flint HJ. Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. J Bacteriol. 2004;186:2099–2106.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Macfarlane GT, Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int. 2012;95:50–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Rios-Covian D, Ruas-Madiedo P, Margolles A, Gueimonde M, de Los Reyes-Gavilan CG, Salazar N. Intestinal short chain fatty acids and their link with diet and human health. Front Microbiol. 2016;7:185.

    PubMed  PubMed Central  Google Scholar 

  124. Cummings JH, Pomare EW, Branch WJ, Naylor CP, Macfarlane GT. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut. 1987;28:1221–1227.

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Annison G, Illman RJ, Topping DL. Acetylated, propionylated or butyrylated starches raise large bowel short-chain fatty acids preferentially when fed to rats. J Nutr. 2003;133:3523–3528.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Gao Z, Yin J, Zhang J, et al. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes. 2009;58:1509–1517.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Yanase H, Takebe K, Nio-Kobayashi J, Takahashi-Iwanaga H, Iwanaga T. Cellular expression of a sodium-dependent monocarboxylate transporter (Slc5a8) and the MCT family in the mouse kidney. Histochem Cell Biol. 2008;130:957–966.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Miyauchi S, Gopal E, Babu E, et al. Sodium-coupled electrogenic transport of pyroglutamate (5-oxoproline) via SLC5A8, a monocarboxylate transporter. Biochim Biophys Acta. 2010;1798:1164–1171.

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Halestrap AP, Wilson MC. The monocarboxylate transporter family–role and regulation. IUBMB Life. 2012;64:109–119.

    CAS  PubMed  PubMed Central  Google Scholar 

  130. Karaki S, Mitsui R, Hayashi H, et al. Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res. 2006;324:353–360.

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Sleeth ML, Thompson EL, Ford HE, Zac-Varghese SE, Frost G. Free fatty acid receptor 2 and nutrient sensing: a proposed role for fibre, fermentable carbohydrates and short-chain fatty acids in appetite regulation. Nutr Res Rev. 2010;23:135–145.

    CAS  Google Scholar 

  132. Eberle JA, Widmayer P, Breer H. Receptors for short-chain fatty acids in brush cells at the “gastric groove”. Front Physiol. 2014;5:152.

    PubMed  PubMed Central  Google Scholar 

  133. Tazoe H, Otomo Y, Kaji I, Tanaka R, Karaki SI, Kuwahara A. Roles of short-chain fatty acids receptors, GPR41 and GPR43 on colonic functions. J Physiol Pharmacol. 2008;59(Suppl 2):251–262.

    PubMed  PubMed Central  Google Scholar 

  134. Nohr MK, Pedersen MH, Gille A, et al. GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Endocrinology. 2013;154:3552–3564.

    PubMed  PubMed Central  Google Scholar 

  135. Sina C, Gavrilova O, Forster M, et al. G protein-coupled receptor 43 is essential for neutrophil recruitment during intestinal inflammation. J Immunol. 2009;183:7514–7522.

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Brown AJ, Goldsworthy SM, Barnes AA, et al. The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. J Biol Chem. 2003;278:11312–11319.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Voltolini C, Battersby S, Etherington SL, Petraglia F, Norman JE, Jabbour HN. A novel antiinflammatory role for the short-chain fatty acids in human labor. Endocrinology. 2012;153:395–403.

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Shapiro H, Thaiss CA, Levy M, Elinav E. The cross talk between microbiota and the immune system: metabolites take center stage. Curr Opin Immunol. 2014;30:54–62.

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Devillard E, McIntosh FM, Duncan SH, Wallace RJ. Metabolism of linoleic acid by human gut bacteria: different routes for biosynthesis of conjugated linoleic acid. J Bacteriol. 2007;189:2566–2570.

    CAS  PubMed  PubMed Central  Google Scholar 

  140. McIntosh FM, Shingfield KJ, Devillard E, Russell WR, Wallace RJ. Mechanism of conjugated linoleic acid and vaccenic acid formation in human faecal suspensions and pure cultures of intestinal bacteria. Microbiology. 2009;155:285–294.

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Gorissen L, Raes K, Weckx S, et al. Production of conjugated linoleic acid and conjugated linolenic acid isomers by Bifidobacterium species. Appl Microbiol Biotechnol. 2010;87:2257–2266.

    CAS  PubMed  PubMed Central  Google Scholar 

  142. Gudbrandsen OA, Rodriguez E, Wergedahl H, et al. Trans-10, cis-12-conjugated linoleic acid reduces the hepatic triacylglycerol content and the leptin mRNA level in adipose tissue in obese Zucker fa/fa rats. Br J Nutr. 2009;102:803–815.

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Toomey S, Harhen B, Roche HM, Fitzgerald D, Belton O. Profound resolution of early atherosclerosis with conjugated linoleic acid. Atherosclerosis. 2006;187:40–49.

    CAS  PubMed  PubMed Central  Google Scholar 

  144. Said HM, Mohammed ZM. Intestinal absorption of water-soluble vitamins: an update. Curr Opin Gastroenterol. 2006;22:140–146.

    PubMed  PubMed Central  Google Scholar 

  145. Ichihashi T, Takagishi Y, Uchida K, Yamada H. Colonic absorption of menaquinone-4 and menaquinone-9 in rats. J Nutr. 1992;122:506–512.

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev. 1997;6(Suppl 1):S43–S45.

    PubMed  PubMed Central  Google Scholar 

  147. Gill SR, Pop M, Deboy RT, et al. Metagenomic analysis of the human distal gut microbiome. Science. 2006;312:1355–1359.

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Bhaskaram P. Micronutrient malnutrition, infection, and immunity: an overview. Nutr Rev. 2002;60:S40–S45.

    Google Scholar 

  149. Cheng CH, Chang SJ, Lee BJ, Lin KL, Huang YC. Vitamin B6 supplementation increases immune responses in critically ill patients. Eur J Clin Nutr. 2006;60:1207–1213.

    CAS  PubMed  PubMed Central  Google Scholar 

  150. Meydani SN, Meydani M, Blumberg JB, et al. Vitamin E supplementation and in vivo immune response in healthy elderly subjects: a randomized controlled trial. JAMA. 1997;277:1380–1386.

    CAS  Google Scholar 

  151. Tamura J, Kubota K, Murakami H, et al. Immunomodulation by vitamin B12: augmentation of CD8+ T lymphocytes and natural killer (NK) cell activity in vitamin B12-deficient patients by methyl-B12 treatment. Clin Exp Immunol. 1999;116:28–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  152. Said HM. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas. Am J Physiol Gastrointest Liver Physiol. 2013;305:G601–G610.

    CAS  PubMed  PubMed Central  Google Scholar 

  153. Magnusdottir S, Ravcheev D, de Crecy-Lagard V, Thiele I. Systematic genome assessment of B-vitamin biosynthesis suggests co-operation among gut microbes. Front Genet. 2015;6:148.

    PubMed  PubMed Central  Google Scholar 

  154. LeBlanc JG, Milani C, de Giori GS, Sesma F, van Sinderen D, Ventura M. Bacteria as vitamin suppliers to their host: a gut microbiota perspective. Curr Opin Biotechnol. 2013;24:160–168.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Engevik MA, Morra CN, Roth D, et al. Microbial metabolic capacity for intestinal folate production and modulation of host folate receptors. Front Microbiol. 2019;10:2305.

    PubMed  PubMed Central  Google Scholar 

  156. Thomas CM, Saulnier DM, Spinler JK, et al. FolC2-mediated folate metabolism contributes to suppression of inflammation by probiotic Lactobacillus reuteri. Microbiologyopen. 2016;5:802–818.

    CAS  PubMed  PubMed Central  Google Scholar 

  157. Spinler JK, Sontakke A, Hollister EB, et al. From prediction to function using evolutionary genomics: human-specific ecotypes of Lactobacillus reuteri have diverse probiotic functions. Genome Biol Evol. 2014;6:1772–1789.

    CAS  PubMed  PubMed Central  Google Scholar 

  158. Olsen I, Amano A. Outer membrane vesicles–offensive weapons or good Samaritans? J Oral Microbiol. 2015;7:27468.

    Google Scholar 

  159. Gurung M, Moon DC, Choi CW, et al. Staphylococcus aureus produces membrane-derived vesicles that induce host cell death. PloS one. 2011;6:e27958.

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Berleman J, Auer M. The role of bacterial outer membrane vesicles for intra- and interspecies delivery. Environ Microbiol. 2013;15:347–354.

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Furuta N, Takeuchi H, Amano A. Entry of Porphyromonas gingivalis outer membrane vesicles into epithelial cells causes cellular functional impairment. Infect Immun. 2009;77:4761–4770.

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–118.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Lee YK, Mazmanian SK. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science. 2010;330:1768–1773.

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Shen Y, Giardino Torchia ML, Lawson GW, Karp CL, Ashwell JD, Mazmanian SK. Outer membrane vesicles of a human commensal mediate immune regulation and disease protection. Cell Host Microbe. 2012;12:509–520.

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453:620–625.

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Lee YK, Menezes JS, Umesaki Y, Mazmanian SK. Proinflammatory T-cell responses to gut microbiota promote experimental autoimmune encephalomyelitis. Proc Natl Acad Sci USA. 2011;108(Suppl 1):4615–4622.

    CAS  PubMed  PubMed Central  Google Scholar 

  167. Ochoa-Reparaz J, Mielcarz DW, Ditrio LE, et al. Central nervous system demyelinating disease protection by the human commensal Bacteroides fragilis depends on polysaccharide A expression. J Immunol. 2010;185:4101–4108.

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Hsiao EY, McBride SW, Hsien S, et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell. 2013;155:1451–1463.

    CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the NIH T32 Grant 5T32DK007664-28 awarded to WR, NIH U01CA170930 Grant awarded to JV, the NLM Training Program in Biomedical Informatics and Data Science T15LM007093 (SCD) awarded to JV, and the Digestive Diseases Center which is funded by NIH/NIDDK P30 DK56338-06A2 Grant awarded to JV.

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Affiliations

  1. Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA

    Wenly Ruan

  2. Section of Gastroenterology, Hepatology, and Nutrition, Texas Children’s Hospital, Houston, TX, USA

    Wenly Ruan

  3. Department of Pathology & Immunology, Baylor College of Medicine, Houston, TX, USA

    Melinda A. Engevik, Jennifer K. Spinler & James Versalovic

  4. Department of Pathology, Texas Children’s Hospital, 1102 Bates St., Feigin Tower Suite 830, Houston, TX, 77030, USA

    Melinda A. Engevik, Jennifer K. Spinler & James Versalovic

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  1. Wenly Ruan
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  2. Melinda A. Engevik
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  3. Jennifer K. Spinler
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  4. James Versalovic
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Correspondence to James Versalovic.

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Disclosures

JV receives unrestricted research support from BioGaia AB, a Swedish probiotics company. JV serves on the scientific advisory board of Seed, a USA-based probiotics/prebiotics company. JV serves on the scientific advisory board of Biomica, an Israeli informatics enterprise, and on the scientific advisory board of Plexus Worldwide, a USA-based nutrition company.

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Ruan, W., Engevik, M.A., Spinler, J.K. et al. Healthy Human Gastrointestinal Microbiome: Composition and Function After a Decade of Exploration. Dig Dis Sci 65, 695–705 (2020). https://doi.org/10.1007/s10620-020-06118-4

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Keywords

  • Microbiome
  • Human
  • Healthy
  • Metabolites