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Cited by 2,015Gut microbiota and healthInflammatory Bowel DiseaseGastrointestinal motility and disorders

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Gut microbiota-derived metabolites as key actors in inflammatory bowel disease

Lavelle, Aonghus, Sokol, Harry·2020·Nature Reviews Gastroenterology & Hepatology
DOI 10.1038/s41575-019-0258-z
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Abstract

A key role of the gut microbiota in the establishment and maintenance of health, as well as in the pathogenesis of disease, has been identified over the past two decades. One of the primary modes by which the gut microbiota interacts with the host is by means of metabolites, which are small molecules that are produced as intermediate or end products of microbial metabolism. These metabolites can derive from bacterial metabolism of dietary substrates, modification of host molecules, such as bile acids, or directly from bacteria. Signals from microbial metabolites influence immune maturation, immune homeostasis, host energy metabolism and maintenance of mucosal integrity. Alterations in the composition and function of the microbiota have been described in many studies on IBD. Alterations have also been described in the metabolite profiles of patients with IBD. Furthermore, specific classes of metabolites, notably bile acids, short-chain fatty acids and tryptophan metabolites, have been implicated in the pathogenesis of IBD. This Review aims to define the key classes of microbial-derived metabolites that are altered in IBD, describe the pathophysiological basis of these associations and identify future targets for precision therapeutic modulation.

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Research works printed but not linked: 131

  1. Cummings, J. H. & Macfarlane, G. T. Role of intestinal bacteria in nutrient metabolism. JPEN J. Parenter. Enter. Nutr. 21, 357–365 (1997). · DOI
  2. Buffie, C. G. et al. Precision microbiome reconstitution restores bile acid mediated resistance to Clostridium difficile. Nature 517, 205–208 (2015). · DOI · Paper page
  3. Cordain, L. et al. Origins and evolution of the western diet: health implications for the 21st century. Am. J. Clin. Nutr. 81, 341–354 (2005). · DOI · Paper page
  4. Ng, S. C. et al. Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390, 2769–2778 (2017). · DOI · Paper page
  5. Burisch, J., Jess, T., Martinato, M. & Lakatos, P. L. The burden of inflammatory bowel disease in Europe. J. Crohns Colitis 7, 322–337 (2013). · DOI
  6. Knights, D., Lassen, K. G. & Xavier, R. J. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome. Gut 62, 1505–1510 (2013). · DOI · Paper page
  7. Krishnan, S. et al. Gut microbiota-derived tryptophan metabolites modulate inflammatory response in hepatocytes and macrophages. Cell Rep. 23, 1099–1111 (2018). · DOI · Paper page
  8. Wikoff, W. R. et al. Metabolomics analysis reveals large effects of gut microflora on mammalian blood metabolites. Proc. Natl Acad. Sci. USA 106, 3698–3703 (2009). This study identifies the importance of microbial-derived metabolites on the host blood metabolome. · DOI · Paper page
  9. Claus, S. P. et al. Systemic multicompartmental effects of the gut microbiome on mouse metabolic phenotypes. Mol. Syst. Biol. 4, 219 (2008). · DOI · Paper page
  10. Yap, I. K. et al. Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse. J. Proteome Res. 7, 3718–3728 (2008). · DOI
  11. Swann, J. R. et al. Variation in antibiotic-induced microbial recolonization impacts on the host metabolic phenotypes of rats. J. Proteome Res. 10, 3590–3603 (2011). · DOI
  12. Zierer, J. et al. The fecal metabolome as a functional readout of the gut microbiome. Nat. Genet. 50, 790–795 (2018). · DOI
  13. Pascal, V. et al. A microbial signature for Crohn’s disease. Gut 66, 813–822 (2017). · DOI
  14. Morgan, X. C. et al. Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biol. 13, R79 (2012). · DOI · Paper page
  15. Schirmer, M. et al. Dynamics of metatranscription in the inflammatory bowel disease gut microbiome. Nat. Microbiol. 3, 337–346 (2018). · DOI
  16. Zhang, A., Sun, H., Wang, P., Han, Y. & Wang, X. Modern analytical techniques in metabolomics analysis. Analyst 137, 293–300 (2012). · DOI
  17. Melnik, A. V. et al. Coupling targeted and untargeted mass spectrometry for metabolome-microbiome-wide association studies of human fecal samples. Anal. Chem. 89, 7549–7559 (2017). · DOI · Paper page
  18. Mushtaq, M. Y., Choi, Y. H., Verpoorte, R. & Wilson, E. G. Extraction for metabolomics: access to the metabolome. Phytochem. Anal. 25, 291–306 (2014). · DOI
  19. Guijas, C. et al. METLIN: a technology platform for identifying knowns and unknowns. Anal. Chem. 90, 3156–3164 (2018). · DOI
  20. Wishart, D. S. et al. HMDB: the human metabolome database. Nucleic Acids Res. 35, D521–D526 (2007). · DOI
  21. Peisl, B. Y. L., Schymanski, E. L. & Wilmes, P. Dark matter in host-microbiome metabolomics: tackling the unknowns — a review. Anal. Chim. Acta 1037, 13–27 (2018). · DOI
  22. Tsugawa, H. Advances in computational metabolomics and databases deepen the understanding of metabolisms. Curr. Opin. Biotechnol. 54, 10–17 (2018). · DOI
  23. Jansson, J. et al. Metabolomics reveals metabolic biomarkers of Crohn’s disease. PLoS One 4, e6386 (2009). · DOI
  24. Le Gall, G. et al. Metabolomics of fecal extracts detects altered metabolic activity of gut microbiota in ulcerative colitis and irritable bowel syndrome. J. Proteome Res. 10, 4208–4218 (2011). · DOI · Paper page
  25. De Preter, V. et al. Faecal metabolite profiling identifies medium-chain fatty acids as discriminating compounds in IBD. Gut 64, 447–458 (2015). · DOI
  26. Santoru, M. L. et al. Cross sectional evaluation of the gut-microbiome metabolome axis in an Italian cohort of IBD patients. Sci. Rep. 7, 9523 (2017). · DOI
  27. Marchesi, J. R. et al. Rapid and noninvasive metabonomic characterization of inflammatory bowel disease. J. Proteome Res. 6, 546–551 (2007). · DOI
  28. Bjerrum, J. T. et al. Metabonomics of human fecal extracts characterize ulcerative colitis, Crohn’s disease and healthy individuals. Metabolomics 11, 122–133 (2015). · DOI
  29. Kolho, K.-L., Pessia, A., Jaakkola, T., de Vos, W. M. & Velagapudi, V. Faecal and serum metabolomics in paediatric inflammatory bowel disease. J. Crohns Colitis 11, 321–334 (2017). · DOI
  30. Jacobs, J. P. et al. A disease-associated microbial and metabolomics state in relatives of pediatric inflammatory bowel disease patients. Cell. Mol. Gastroenterol. Hepatol. 2, 750–766 (2016). This study uses microbiome and metabolome analysis of paediatric patients with IBD and their relatives to identify IBD-associated metabotypes. · DOI
  31. Williams, H. R. et al. Characterization of inflammatory bowel disease with urinary metabolic profiling. Am. J. Gastroenterol. 104, 1435–1444 (2009). · DOI
  32. Williams, H. R. et al. Differences in gut microbial metabolism are responsible for reduced hippurate synthesis in Crohn’s disease. BMC Gastroenterol. 10, 108 (2010). · DOI
  33. Schicho, R. et al. Quantitative metabolomic profiling of serum, plasma, and urine by 1H NMR spectroscopy discriminates between patients with inflammatory bowel disease and healthy individuals. J. Proteome Res. 11, 3344–3357 (2012). · DOI
  34. Stephens, N. S. et al. Urinary NMR metabolomic profiles discriminate inflammatory bowel disease from healthy. J. Crohns Colitis 7, e42–e48 (2013). · DOI
  35. Dawiskiba, T. et al. Serum and urine metabolomic fingerprinting in diagnostics of inflammatory bowel diseases. World J. Gastroenterol. 20, 163–174 (2014). · DOI
  36. Ooi, M. et al. GC/MS-based profiling of amino acids and TCA cycle-related molecules in ulcerative colitis. Inflamm. Res. 60, 831–840 (2011). · DOI
  37. Hisamatsu, T. et al. Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. PLoS One 7, e31131 (2012). · DOI
  38. Zhang, Y. et al. 1H NMR-based spectroscopy detects metabolic alterations in serum of patients with early-stage ulcerative colitis. Biochem. Biophys. Res. Commun. 433, 547–551 (2013). · DOI
  39. Bezabeh, T. et al. The use of 1H magnetic resonance spectroscopy in inflammatory bowel diseases: distinguishing ulcerative colitis from Crohn’s disease. Am. J. Gastroenterol. 96, 442–448 (2001). · DOI
  40. Lees, H. J., Swann, J. R., Wilson, I. D., Nicholson, J. K. & Holmes, E. Hippurate: the natural history of a mammalian–microbial cometabolite. J. Proteome Res. 12, 1527–1546 (2013). · DOI
  41. Lai, Y. et al. Serum metabolomics identifies altered bioenergetics, signaling cascades in parallel with exposome markers in Crohn’s disease. Molecules 24, 449 (2019). · DOI
  42. Sonnenburg, E. D. & Sonnenburg, J. L. Starving our microbial self: the deleterious consequences of a diet deficient in microbiota-accessible carbohydrates. Cell Metab. 20, 779–786 (2014). · DOI
  43. Velázquez, M., Davies, C., Marett, R., Slavin, J. L. & Feirtag, J. M. Effect of oligosaccharides and fibre substitutes on short-chain fatty acid production by human faecal microflora. Anaerobe 6, 87–92 (2000). · DOI
  44. Salonen, A. et al. Impact of diet and individual variation on intestinal microbiota composition and fermentation products in obese men. ISME J. 8, 2218–2230 (2014). · DOI · Paper page
  45. Hall, A. B. et al. A novel Ruminococcus gnavus clade enriched in inflammatory bowel disease patients. Genome Med. 9, 103 (2017). · DOI · Paper page
  46. Davie, J. R. Inhibition of histone deacetylase activity by butyrate. J. Nutr. 133, 2485S–2493S (2003). · DOI · Paper page
  47. Singh, N. et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40, 128–139 (2014). · DOI · Paper page
  48. Frost, G. et al. The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nat. Commun. 5, 3611 (2014). · DOI · Paper page
  49. Kimura, I. et al. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat. Commun. 4, 1829 (2013). · DOI · Paper page
  50. Larraufie, P. et al. SCFAs strongly stimulate PYY production in human enteroendocrine cells. Sci. Rep. 8, 74 (2018). · DOI
  51. Kaiko, G. E. et al. The colonic crypt protects stem cells from microbiota-derived metabolites. Cell 165, 1708–1720 (2016). · DOI
  52. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008). · DOI · Paper page
  53. Machiels, K. et al. A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut 63, 1275–1283 (2014). · DOI · Paper page
  54. Harig, J. M., Soergel, K. H., Komorowski, R. A. & Wood, C. M. Treatment of diversion colitis with short-chain-fatty acid irrigation. N. Engl. J. Med. 320, 23–28 (1989). · DOI
  55. Vernia, P. et al. Short-chain fatty acid topical treatment in distal ulcerative colitis. Aliment. Pharmacol. Ther. 9, 309–313 (1995). · DOI
  56. Hanai, H. et al. Germinated barley foodstuff prolongs remission in patients with ulcerative colitis. Int. J. Mol. Med. 13, 643–647 (2004).
  57. Fernández-Bañares, F. et al. Randomized clinical trial of Plantago ovata seeds (dietary fiber) as compared with mesalamine in maintaining remission in ulcerative colitis. Am. J. Gastroenterol. 94, 427–433 (1999). · DOI
  58. Roediger, W. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet 316, 712–715 (1980). · DOI
  59. De Preter, V. et al. Impaired butyrate oxidation in ulcerative colitis is due to decreased butyrate uptake and a defect in the oxidation pathway. Inflamm. Bowel Dis. 18, 1127–1136 (2011). · DOI
  60. Vernia, P. et al. Fecal lactate and ulcerative colitis. Gastroenterology 95, 1564–1568 (1988). · DOI
  61. Vernia, P., Gnaedinger, A., Hauck, W. & Breuer, R. I. Organic anions and the diarrhea of inflammatory bowel disease. Dig. Dis. Sci. 33, 1353–1358 (1988). · DOI
  62. Takaishi, H. et al. Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. Int. J. Med. Microbiol. 298, 463–472 (2008). · DOI
  63. Louis, P. et al. Restricted distribution of the butyrate kinase pathway among butyrate-producing bacteria from the human colon. J. Bacteriol. 186, 2099–2106 (2004). · DOI
  64. Laserna-Mendieta, E. J. et al. Determinants of reduced genetic capacity for butyrate synthesis by the gut microbiome in Crohn’s disease and ulcerative colitis. J. Crohns Colitis 12, 204–216 (2017). · DOI
  65. Hove, H. & Mortensen, P. B. Influence of intestinal inflammation (IBD) and small and large bowel length on fecal short-chain fatty acids and lactate. Dig. Dis. Sci. 40, 1372–1380 (1995). · DOI
  66. Quévrain, E. et al. Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn’s disease. Gut 65, 415–425 (2016). · DOI
  67. Tye, H. et al. NLRP1 restricts butyrate producing commensals to exacerbate inflammatory bowel disease. Nat. Commun. 9, 3728 (2018). · DOI
  68. Kim, I. et al. Differential regulation of bile acid homeostasis by the farnesoid X receptor in liver and intestine. J. Lipid Res. 48, 2664–2672 (2007). · DOI
  69. Wang, Y.-D., Chen, W.-D., Yu, D., Forman, B. M. & Huang, W. The G-protein-coupled bile acid receptor, Gpbar1 (TGR5), negatively regulates hepatic inflammatory response through antagonizing nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) in mice. Hepatology 54, 1421–1432 (2011). · DOI
  70. Keitel, V., Donner, M., Winandy, S., Kubitz, R. & Häussinger, D. Expression and function of the bile acid receptor TGR5 in Kupffer cells. Biochem. Biophys. Res. Commun. 372, 78–84 (2008). · DOI · Paper page
  71. Calmus, Y. et al. Differential effects of chenodeoxycholic and ursodeoxycholic acids on interleukin 1, interleukin 6 and tumor necrosis factor-α production by monocytes. Hepatology 16, 719–723 (1992). · DOI
  72. Huang, W. et al. Nuclear receptor-dependent bile acid signaling is required for normal liver regeneration. Science 312, 233–236 (2006). · DOI · Paper page
  73. Jones, B. V., Begley, M., Hill, C., Gahan, C. G. M. & Marchesi, J. R. Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proc. Natl Acad. Sci. USA 105, 13580–13585 (2008). · DOI · Paper page
  74. Joyce, S. A. et al. Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Proc. Natl Acad. Sci. USA 111, 7421–7426 (2014). An important study that highlights the profound host effects of bile acid transformation by a gut bacteria on the host. · DOI · Paper page
  75. Labbé, A., Ganopolsky, J. G., Martoni, C. J., Prakash, S. & Jones, M. L. Bacterial bile metabolising gene abundance in Crohn’s, ulcerative colitis and type 2 diabetes metagenomes. PLoS One 9, e115175 (2014). · DOI
  76. Lorenzo-Zuniga, V. et al. Oral bile acids reduce bacterial overgrowth, bacterial translocation, and endotoxemia in cirrhotic rats. Hepatology 37, 551–557 (2003). · DOI · Paper page
  77. D’Aldebert, E. et al. Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium. Gastroenterology 136, 1435–1443 (2009). · DOI
  78. Termen, S. et al. PU.1 and bacterial metabolites regulate the human gene CAMP encoding antimicrobial peptide LL-37 in colon epithelial cells. Mol. Immunol. 45, 3947–3955 (2008). · DOI
  79. Islam, K. B. M. S. et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 141, 1773–1781 (2011). · DOI · Paper page
  80. Jung, D., Fantin, A. C., Scheurer, U., Fried, M. & Kullak-Ublick, G. A. Human ileal bile acid transporter gene ASBT (SLC10A2) is transactivated by the glucocorticoid receptor. Gut 53, 78–84 (2004). · DOI
  81. Jahnel, J. et al. Inflammatory bowel disease alters intestinal bile acid transporter expression. Drug Metab. Dispos. 42, 1423–1431 (2014). · DOI
  82. Nyhlin, H., Merrick, M. V. & Eastwood, M. A. Bile acid malabsorption in Crohn’s disease and indications for its assessment using SeHCAT. Gut 35, 90–93 (1994). · DOI
  83. Song, X. et al. Microbial bile acid metabolites modulate gut RORγ+ regulatory T cell homeostasis. Nature 577, 410–415 (2020). · DOI · Paper page
  84. Vantrappen, G., Ghoos, Y., Rutgeerts, P. & Janssens, J. Bile acid studies in uncomplicated Crohn’s disease. Gut 18, 730–735 (1977). · DOI
  85. Rutgeerts, P., Ghoos, Y. & Vantrappen, G. Kinetics of primary bile acids in patients with non-operated Crohn’s disease. Eur. J. Clin. Invest. 12, 135–143 (1982). · DOI
  86. Kruis, W., Kalek, H. D., Stellaard, F. & Paumgartner, G. Altered fecal bile acid pattern in patients with inflammatory bowel disease. Digestion 35, 189–198 (1986). · DOI
  87. Torres, J. et al. The gut microbiota, bile acids and their correlation in primary sclerosing cholangitis associated with inflammatory bowel disease. United European Gastroenterol. J. 6, 112–122 (2018). · DOI
  88. Duboc, H. et al. Connecting dysbiosis, bile-acid dysmetabolism and gut inflammation in inflammatory bowel diseases. Gut 62, 531–539 (2013). This study identifies potential associations between bile acids and the microbiota in IBD. · DOI · Paper page
  89. McGarr, S. E., Ridlon, J. M. & Hylemon, P. B. Diet, anaerobic bacterial metabolism, and colon cancer: a review of the literature. J. Clin. Gastroenterol. 39, 98–109 (2005).
  90. Côté, F. et al. Disruption of the nonneuronal tph1 gene demonstrates the importance of peripheral serotonin in cardiac function. Proc. Natl Acad. Sci. USA 100, 13525–13530 (2003). · DOI
  91. Yano, J. M. et al. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis. Cell 161, 264–276 (2015). · DOI · Paper page
  92. Desbonnet, L. et al. Gut microbiota depletion from early adolescence in mice: implications for brain and behaviour. Brain Behav. Immun. 48, 165–173 (2015). · DOI · Paper page
  93. Reigstad, C. S. et al. Gut microbes promote colonic serotonin production through an effect of short-chain fatty acids on enterochromaffin cells. FASEB J. 29, 1395–1403 (2015). · DOI · Paper page
  94. Zenewicz, L. A. et al. Innate and adaptive interleukin-22 protects mice from inflammatory bowel disease. Immunity 29, 947–957 (2008). · DOI
  95. Qiu, J. et al. The aryl hydrocarbon receptor regulates gut immunity through modulation of innate lymphoid cells. Immunity 36, 92–104 (2012). · DOI
  96. Li, Y. et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147, 629–640 (2011). · DOI
  97. Venkatesh, M. et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41, 296–310 (2014). · DOI · Paper page
  98. Nikolaus, S. et al. Increased tryptophan metabolism is associated with activity of inflammatory bowel diseases. Gastroenterology 153, 1504–1516.e2 (2017). An important study that identifies the link between tryptophan metabolism and IBD in a large clinical cohort. · DOI
  99. Lamas, B. et al. CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands. Nat. Med. 22, 598–605 (2016). · DOI · Paper page
  100. Monteleone, I. et al. Aryl hydrocarbon receptor-induced signals up-regulate IL-22 production and inhibit inflammation in the gastrointestinal tract. Gastroenterology 141, 237–248, 248.e1 (2011). · DOI · Paper page
  101. Takamura, T. et al. Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis. Immunol. Cell Biol. 89, 817–822 (2011). · DOI
  102. Wlodarska, M. et al. Indoleacrylic acid produced by commensal peptostreptococcus species suppresses inflammation. Cell Host Microbe 22, 25–37.e6 (2017). · DOI
  103. Mills, E. L. et al. Succinate dehydrogenase supports metabolic repurposing of mitochondria to drive inflammatory macrophages. Cell 167, 457–470.e13 (2016). · DOI · Paper page
  104. De Vadder, F. et al. Microbiota-produced succinate improves glucose homeostasis via intestinal gluconeogenesis. Cell Metab. 24, 151–157 (2016). · DOI
  105. Macias-Ceja, D. C. et al. Succinate receptor mediates intestinal inflammation and fibrosis. Mucosal Immunol. 12, 178–187 (2019). · DOI
  106. Osaka, T. et al. Meta-analysis of fecal microbiota and metabolites in experimental colitic mice during the inflammatory and healing phases. Nutrients 9, 1329 (2017). · DOI
  107. Garner, C. E. et al. Volatile organic compounds from feces and their potential for diagnosis of gastrointestinal disease. FASEB J. 21, 1675–1688 (2007). · DOI
  108. Mane, J. et al. Partial replacement of dietary (n-6) fatty acids with medium-chain triglycerides decreases the incidence of spontaneous colitis in interleukin-10-deficient mice. J. Nutr. 139, 603–610 (2009). · DOI
  109. Baur, P. et al. Metabolic phenotyping of the Crohn’s disease-like IBD etiopathology in the TNFΔARE/WT mouse model. J. Proteome Res. 10, 5523–5535 (2011). · DOI
  110. Donia, M. S. & Fischbach, M. A. Small molecules from the human microbiota. Science 349, 1254766 (2015). · DOI · Paper page
  111. Milshteyn, A., Colosimo, D. A. & Brady, S. F. Accessing bioactive natural products from the human microbiome. Cell Host Microbe 23, 725–736 (2018). · DOI
  112. Guo, C.-J. et al. Discovery of reactive microbiota-derived metabolites that inhibit host proteases. Cell 168, 517–526.e18 (2017). · DOI
  113. Chen, H. et al. A forward chemical genetic screen reveals gut microbiota metabolites that modulate host physiology. Cell 177, 1217–1231.e18 (2019). · DOI
  114. Fitzgerald, C. B. et al. Comparative analysis of Faecalibacterium prausnitzii genomes shows a high level of genome plasticity and warrants separation into new species-level taxa. BMC Genomics 19, 931–931 (2018). · DOI
  115. Martin, R. et al. The commensal bacterium Faecalibacterium prausnitzii is protective in DNBS-induced chronic moderate and severe colitis models. Inflamm. Bowel Dis. 20, 417–430 (2014). · DOI · Paper page
  116. Martín, R. et al. Functional characterization of novel Faecalibacterium prausnitzii strains isolated from healthy volunteers: a step forward in the use of F. prausnitzii as a next-generation probiotic. Front. Microbiol. 8, 1226–1226 (2017). · DOI · Paper page
  117. Gionchetti, P. et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119, 305–309 (2000). · DOI
  118. Yasueda, A. et al. The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis. Surg. Today 46, 939–949 (2016). · DOI
  119. Francis, M. B., Allen, C. A., Shrestha, R. & Sorg, J. A. Bile acid recognition by the Clostridium difficile germinant receptor, CspC, is important for establishing infection. PLOS Pathog. 9, e1003356 (2013). · DOI
  120. Weingarden, A. R. et al. Microbiota transplantation restores normal fecal bile acid composition in recurrent Clostridium difficile infection. Am. J. Physiol. Gastrointest. Liver Physiol. 306, G310–G319 (2014). · DOI · Paper page
  121. Moayyedi, P. et al. Fecal microbiota transplantation induces remission in patients with active ulcerative colitis in a randomized controlled trial. Gastroenterology 149, 102–109.e6 (2015). · DOI · Paper page
  122. Costello, S. P. et al. Effect of fecal microbiota transplantation on 8-week remission in patients with ulcerative colitis: a randomized clinical trial. JAMA 321, 156–164 (2019). · DOI
  123. Nusbaum, D. J. et al. Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients. FEMS Microbiol. Ecol. 94, fiy133 (2018). · DOI
  124. Misra, B. et al. P421 SER-287, an investigational microbiome therapeutic, induces remission and endoscopic improvement in a placebo-controlled, double-blind randomised trial in patients with active mild-to-moderate ulcerative colitis. J. Crohns Colitis 12, S317–S317 (2018). · DOI
  125. Vedanta Biosciences. Vedanta Biosciences announces initiation of phase 1 clinical study with Janssen of microbiome-derived product candidate for inflammatory bowel disease. Vedanta Biosciences https://www.vedantabio.com/news-media/press-releases/detail/2491/vedanta-biosciences-announces-initiation-of-phase-1 (2019).
  126. Fangmann, D. et al. Targeted microbiome intervention by microencapsulated delayed-release niacin beneficially affects insulin sensitivity in humans. Diabetes Care 41, 398–405 (2018). · DOI
  127. Li, J. et al. Niacin ameliorates ulcerative colitis via prostaglandin D2-mediated D prostanoid receptor 1 activation. EMBO Mol. Med. 9, 571–588 (2017). · DOI
  128. Sahuri-Arisoylu, M. et al. Reprogramming of hepatic fat accumulation and ‘browning’ of adipose tissue by the short-chain fatty acid acetate. Int. J. Obes. 40, 955 (2016). · DOI
  129. Costea, P. I. et al. Towards standards for human fecal sample processing in metagenomic studies. Nat. Biotechnol. 35, 1069–1076 (2017). · DOI · Paper page
  130. Rodrigues, R. R., Shulzhenko, N. & Morgun, A. Transkingdom networks: a systems biology approach to identify causal members of host-microbiota interactions. Methods Mol. Biol. 1849, 227–242 (2018). · DOI
  131. Stappenbeck, T. S. & Virgin, H. W. Accounting for reciprocal host–microbiome interactions in experimental science. Nature 534, 191 (2016). · DOI

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Metadata

Authors
Lavelle, A., & Sokol, H.
Affiliations
Inserm (FR)
Corresponding author
Sokol, Harry
ORCID
Venue
Nature Reviews Gastroenterology & Hepatology
Publisher
Springer Science and Business Media LLC
Published
2020-02-19
Volume
17
Issue
4
Pages
223-237
ISSN
  • 1759-5045 (ISSN-L)
  • 1759-5053
DOI
10.1038/s41575-019-0258-z
OpenAlex
W3006796998
Cited by
2,015
References
0
Citations by year
2026: 324 · 2025: 392 · 2024: 410 · 2023: 318 · 2022: 315 · 2021: 197 · 2020: 58
FWCI
21.35
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • Nature Reviews Gastroenterology & Hepatology (publishedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Keywords
gut microbiota, microbial metabolites, inflammatory bowel disease, bile acids, short-chain fatty acids, tryptophan metabolites, host-microbe interactions, immune homeostasis, mucosal integrity, energy metabolism, IBD pathogenesis, precision therapy
MeSH terms
Gastrointestinal Microbiome, Fecal Microbiota Transplantation, Animals, Bile Acids and Salts, Fatty Acids, Volatile, Humans, Tryptophan, Inflammatory Bowel Diseases, Probiotics, Gastrointestinal Tract, Metabolomics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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