Healthy Human Gastrointestinal Microbiome: Composition and Function After a Decade of Exploration (original) (raw)

• 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
• Bull MJ, Plummer NT. Part 1: The human gut microbiome in health and disease. Integr Med. 2014;13:17–22.
  Google Scholar
• Rath CM, Dorrestein PC. The bacterial chemical repertoire mediates metabolic exchange within gut microbiomes. Curr Opin Microbiol. 2012;15:147–154.
  CAS PubMed Google Scholar
• 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
• 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
• 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
• Flint HJ. The impact of nutrition on the human microbiome. Nutr Rev. 2012;70:S10–S13.
  PubMed Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• Marcobal A, Sonnenburg JL. Human milk oligosaccharide consumption by intestinal microbiota. Clin Microbiol Infect. 2012;18:12–15.
  CAS PubMed PubMed Central Google Scholar
• 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 Google Scholar
• 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
• 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
• Lloyd-Price J, Abu-Ali G, Huttenhower C. The healthy human microbiome. Genome Med. 2016;8:51.
  PubMed PubMed Central Google Scholar
• 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
• 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
• 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
• 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 Google Scholar
• 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 Google Scholar
• 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
• Human Microbiome Project C. Structure, function and diversity of the healthy human microbiome. Nature. 2012;486:207–214.
  Google Scholar
• Tuddenham S, Sears CL. The intestinal microbiome and health. Curr Opin Infect Dis. 2015;28:464–470.
  CAS PubMed PubMed Central Google Scholar
• 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
• 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 Google Scholar
• 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 Google Scholar
• Berg RD. The indigenous gastrointestinal microflora. Trends Microbiol. 1996;4:430–435.
  CAS PubMed Google Scholar
• Dewhirst FE, Chen T, Izard J, et al. The human oral microbiome. J Bacteriol. 2010;192:5002–5017.
  CAS PubMed PubMed Central Google Scholar
• Vasapolli R, Schutte K, Schulz C et al. Analysis of transcriptionally active bacteria throughout the gastrointestinal tract of healthy individuals. Gastroenterology. 2019.
• 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
• May M, Abrams JA. Emerging insights into the esophageal microbiome. Curr Treat Options Gastroenterol. 2018;16:72–85.
  PubMed PubMed Central Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• 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 Google Scholar
• 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
• 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 Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• Rajilic-Stojanovic M, Heilig HG, Tims S, Zoetendal EG, de Vos WM. Long-term monitoring of the human intestinal microbiota composition. Environ Microbiol. 2012.
• 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
• 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 Google Scholar
• 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
• 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
• 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
• Hall AB, Tolonen AC, Xavier RJ. Human genetic variation and the gut microbiome in disease. Nat Rev Genet. 2017;18:690–699.
  CAS PubMed Google Scholar
• 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 Google Scholar
• Li YH, Tian X. Quorum sensing and bacterial social interactions in biofilms. Sensors (Basel). 2012;12:2519–2538.
  CAS PubMed PubMed Central Google Scholar
• Miller MB, Bassler BL. Quorum sensing in bacteria. Annu Rev Microbiol. 2001;55:165–199.
  CAS PubMed Google Scholar
• Waters CM, Bassler BL. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol. 2005;21:319–346.
  CAS PubMed Google Scholar
• Parsek MR, Greenberg EP. Sociomicrobiology: the connections between quorum sensing and biofilms. Trends Microbiol. 2005;13:27–33.
  CAS PubMed Google Scholar
• Thompson JA, Oliveira RA, Xavier KB. Chemical conversations in the gut microbiota. Gut Microbes. 2016;7:163–170.
  CAS PubMed PubMed Central Google Scholar
• 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
• 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 Google Scholar
• 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
• 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 PubMed Google Scholar
• 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
• 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
• 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
• 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
• 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
• 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
• Ray B, Sandine WE. Acetic, Propionic, and Lactic Acids of Starter Culture Bacteria as Biopreservatives. London: CRC Press; 1992.
  Google Scholar
• 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
• 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 Google Scholar
• Nikaido H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev. 2003;67:593–656.
  CAS PubMed PubMed Central Google Scholar
• 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
• 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 Google Scholar
• 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 Google Scholar
• Florence TM. The production of hydroxyl radical from the reaction between hydrogen peroxide and NADH. J Inorg Biochem. 1986;28:33–37.
  CAS PubMed Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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
• Spinler JK, Auchtung J, Brown A et al. Next-generation probiotics targeting clostridium difficile through precursor-directed antimicrobial biosynthesis. Infect Immun. 2017;85.
• 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
• 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
• 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
• Das NK, Schwartz AJ, Barthel Get al. Microbial metabolite signaling is required for systemic iron homeostasis. Cell Metab. 2019.
• 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
• 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 Google Scholar
• 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
• 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
• 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
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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
• 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
• 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
• Cohen SS. A Guide to the Polyamines. Oxford: Oxford University Press; 1997.
  Google Scholar
• Shah P, Swiatlo E. A multifaceted role for polyamines in bacterial pathogens. Mol Microbiol. 2008;68:4–16.
  CAS PubMed Google Scholar
• 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 Google Scholar
• 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
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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
• 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
• 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 Google Scholar
• 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
• 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
• 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 Google Scholar
• 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 Google Scholar
• 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
• 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 Google Scholar
• 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
• 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
• 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
• Macfarlane GT, Macfarlane S. Bacteria, colonic fermentation, and gastrointestinal health. J AOAC Int. 2012;95:50–60.
  CAS PubMed Google Scholar
• 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
• 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
• 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 Google Scholar
• 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
• 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 Google Scholar
• 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 Google Scholar
• Halestrap AP, Wilson MC. The monocarboxylate transporter family–role and regulation. IUBMB Life. 2012;64:109–119.
  CAS PubMed Google Scholar
• 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 Google Scholar
• 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 PubMed Google Scholar
• 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
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• Said HM, Mohammed ZM. Intestinal absorption of water-soluble vitamins: an update. Curr Opin Gastroenterol. 2006;22:140–146.
  PubMed Google Scholar
• 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 Google Scholar
• Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev. 1997;6(Suppl 1):S43–S45.
  PubMed Google Scholar
• 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
• Bhaskaram P. Micronutrient malnutrition, infection, and immunity: an overview. Nutr Rev. 2002;60:S40–S45.
  PubMed Google Scholar
• 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 Google Scholar
• 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 PubMed Google Scholar
• 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
• 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
• 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
• 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 Google Scholar
• 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
• 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
• 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
• Olsen I, Amano A. Outer membrane vesicles–offensive weapons or good Samaritans? J Oral Microbiol. 2015;7:27468.
  PubMed Google Scholar
• 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
• Berleman J, Auer M. The role of bacterial outer membrane vesicles for intra- and interspecies delivery. Environ Microbiol. 2013;15:347–354.
  CAS PubMed Google Scholar
• 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
• 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 Google Scholar
• 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
• 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
• Mazmanian SK, Round JL, Kasper DL. A microbial symbiosis factor prevents intestinal inflammatory disease. Nature. 2008;453:620–625.
  CAS PubMed Google Scholar
• 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 Google Scholar
• 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 Google Scholar
• 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