Gut microbiota-derived metabolites as key actors in inflammatory bowel disease
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
BA metabolism is defective in patients with IBD, indicated by increased levels of primary BAs and/or their conjugated forms and decreased levels of secondary BAs.
“BA metabolism is defective in patients with IBD, as indicated by increased levels of primary BAs (PBAs) and/or their conjugated forms, accompanied by decreased levels of second BAs (SBAs) (Lavelle and Sokol, 2020; Biagioli et al., 2021; Gallagher et al., 2021).”
From Bacteroides dorei BDX-01 alleviates DSS-induced experimental colitis in mice by regulating intestinal bile salt hydrolase activity and the FXR-NLRP3 signaling pathway (2023) · cites this paper as Lavelle and Sokol, 2020
Cites
Diet rapidly and reproducibly alters the human gut microbiome
David, L. A., Maurice, C. F., Carmody, R. N., Gootenberg, D. B., Button, J. E., Wolfe, B. E., Ling, A. V., Devlin, A. S., Varma, Y., Fischbach, M. A., et al. (2014) · Nature · doi:10.1038/nature12820 · Cited by 10,100 · see citing works
De Filippo, C., Cavalieri, D., Di Paola, M., Ramazzotti, M., Poullet, J. B., Massart, S., Collini, S., Pieraccini, G., & Lionetti, P. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005963107 · Cited by 5,579 · see citing works
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · see citing works
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013) · Science · doi:10.1126/science.1241165 · Cited by 5,413 · see citing works
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,402 · see citing works
Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
Maslowski, K. M., Vieira, A. T., Ng, A., Kranich, J., Sierro, F., Yu, D., Schilter, H. C., Rolph, M. S., Mackay, F., Artis, D., et al. (2009) · Nature · doi:10.1038/nature08530 · Cited by 3,241 · see citing works
Multi-omics of the gut microbial ecosystem in inflammatory bowel diseases
Lloyd-Price, J., Arze, C., Ananthakrishnan, A. N., Schirmer, M., Avila-Pacheco, J., Poon, T. W., Andrews, E., Ajami, N. J., Bonham, K. S., Brislawn, C. J., et al. (2019) · Nature · doi:10.1038/s41586-019-1237-9 · Cited by 3,143 · see citing works
Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome
Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., et al. (2013) · Nature · doi:10.1038/nature12347 · Cited by 2,219 · see citing works
Chang, P. V., Hao, L., Offermanns, S., & Medzhitov, R. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1322269111 · Cited by 2,175 · see citing works
Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10-/- mice
Devkota, S., Wang, Y., Musch, M. W., Leone, V., Fehlner-Peach, H., Nadimpalli, A., Antonopoulos, D. A., Jabri, B., & Chang, E. B. (2012) · Nature · doi:10.1038/nature11225 · Cited by 1,904 · see citing works
Paramsothy, S., Kamm, M. A., Kaakoush, N. O., Walsh, A. J., van den Bogaerde, J., Samuel, D., Leong, R. W. L., Connor, S., Ng, W., Paramsothy, R., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)30182-4 · Cited by 1,276 · see citing works
ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation
Hashimoto, T., Perlot, T., Rehman, A., Trichereau, J., Ishiguro, H., Paolino, M., Sigl, V., Hanada, T., Hanada, R., Lipinski, S., et al. (2012) · Nature · doi:10.1038/nature11228 · Cited by 1,271 · see citing works
Regulation of antibacterial defense in the small intestine by the nuclear bile acid receptor
Inagaki, T., Moschetta, A., Lee, Y.-K., Peng, L., Zhao, G., Downes, M., Yu, R. T., Shelton, J. M., Richardson, J. A., Repa, J. J., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0509592103 · Cited by 1,164 · see citing works
Next-generation probiotics: the spectrum from probiotics to live biotherapeutics
O’Toole, P. W., Marchesi, J. R., & Hill, C. (2017) · Nature Microbiology · doi:10.1038/nmicrobiol.2017.57 · Cited by 971 · see citing works
Rossen, N. G., Fuentes, S., van der Spek, M. J., Tijssen, J. G., Hartman, J. H. A., Duflou, A., Löwenberg, M., van den Brink, G. R., Mathus-Vliegen, E. M. H., de Vos, W. M., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.03.045 · Cited by 921 · see citing works
Gut Microbial Metabolites Fuel Host Antibody Responses
Kim, M., Qie, Y., Park, J., & Kim, C. H. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.07.001 · Cited by 893 · see citing works
Gadaleta, R. M., van Erpecum, K. J., Oldenburg, B., Willemsen, E. C. L., Renooij, W., Murzilli, S., Klomp, L. W. J., Siersema, P. D., Schipper, M. E. I., Danese, S., et al. (2011) · Gut · doi:10.1136/gut.2010.212159 · Cited by 870 · see citing works
Bile acid receptors as targets for drug development
Schaap, F. G., Trauner, M., & Jansen, P. L. M. (2014) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2013.151 · Cited by 696 · see citing works
A weaning reaction to microbiota is required for resistance to immunopathologies in the adult
Al Nabhani, Z., Dulauroy, S., Marques, R., Cousu, C., Al Bounny, S., Déjardin, F., Sparwasser, T., Bérard, M., Cerf-Bensussan, N., & Eberl, G. (2019) · Immunity · doi:10.1016/j.immuni.2019.02.014 · Cited by 679 · see citing works
Gut microbiome interactions with drug metabolism, efficacy, and toxicity
Wilson, I. D., & Nicholson, J. K. (2017) · Translational Research · doi:10.1016/j.trsl.2016.08.002 · Cited by 656 · see citing works
The bile acid receptor FXR is a modulator of intestinal innate immunity
Vavassori, P., Mencarelli, A., Renga, B., Distrutti, E., & Fiorucci, S. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803978 · Cited by 655 · see citing works
The Microbiome Quality Control Project Consortium, Sinha, R., Abu-Ali, G., Vogtmann, E., Fodor, A. A., Ren, B., Amir, A., Schwager, E., Crabtree, J., Ma, S., et al. (2017) · Nature Biotechnology · doi:10.1038/nbt.3981 · Cited by 587 · see citing works
Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells
Chimerel, C., Emery, E., Summers, D. K., Keyser, U., Gribble, F. M., & Reimann, F. (2014) · Cell Reports · doi:10.1016/j.celrep.2014.10.032 · Cited by 548 · see citing works
Understanding the role of gut microbiome–host metabolic signal disruption in health and disease
Holmes, E., Li, J. V., Athanasiou, T., Ashrafian, H., & Nicholson, J. K. (2011) · Trends in Microbiology · doi:10.1016/j.tim.2011.05.006 · Cited by 541 · see citing works
(2014) · Cell Host & Microbe · doi:10.1016/j.chom.2014.08.014 · Cited by 536 · see citing works
Alexeev, E. E., Lanis, J. M., Kao, D. J., Campbell, E. L., Kelly, C. J., Battista, K. D., Gerich, M. E., Jenkins, B. R., Walk, S. T., Kominsky, D. J., et al. (2018) · The American Journal of Pathology · doi:10.1016/j.ajpath.2018.01.011 · Cited by 532 · see citing works
Commensal bacteria make GPCR ligands that mimic human signalling molecules
Cohen, L. J., Esterhazy, D., Kim, S.-H., Lemetre, C., Aguilar, R. R., Gordon, E. A., Pickard, A. J., Cross, J. R., Emiliano, A. B., Han, S. M., et al. (2017) · Nature · doi:10.1038/nature23874 · Cited by 500 · see citing works
Pathways of acetate, propionate, and butyrate formation by the human fecal microbial flora
Miller, T. L., & Wolin, M. J. (1996) · Applied and Environmental Microbiology · doi:10.1128/aem.62.5.1589-1592.1996 · Cited by 481 · see citing works
FGF15/19 Regulates Hepatic Glucose Metabolism by Inhibiting the CREB-PGC-1α Pathway
Potthoff, M. J., Boney-Montoya, J., Choi, M., He, T., Sunny, N. E., Satapati, S., Suino-Powell, K., Xu, H. E., Gerard, R. D., Finck, B. N., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.019 · Cited by 431 · see citing works
Mechanism of growth inhibition by free bile acids in lactobacilli and bifidobacteria
Kurdi, P., Kawanishi, K., Mizutani, K., & Yokota, A. (2006) · Journal of Bacteriology · doi:10.1128/jb.188.5.1979-1986.2006 · Cited by 364 · see citing works
The Gut Microbial Metabolite Trimethylamine-N-Oxide Is Present in Human Cerebrospinal Fluid
Del Rio, D., Zimetti, F., Caffarra, P., Tassotti, M., Bernini, F., Brighenti, F., Zini, A., & Zanotti, I. (2017) · Nutrients · doi:10.3390/nu9101053 · Cited by 172 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Microbiota-derived metabolites as drivers of gut–brain communication
Ahmed, H., Leyrolle, Q., Koistinen, V., Kärkkäinen, O., Layé, S., Delzenne, N., & Hanhineva, K. (2022) · Gut Microbes · doi:10.1080/19490976.2022.2102878 · Cited by 462 · see citing works
Understanding the gut microbiota and sarcopenia: a systematic review
Liu, C., Cheung, W., Li, J., Chow, S. K., Yu, J., Wong, S. H., Ip, M., Sung, J. J. Y., & Wong, R. M. Y. (2021) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12784 · Cited by 363 · see citing works
<i>Ruminococcus gnavus</i> : friend or foe for human health
Crost, E. H., Coletto, E., Bell, A., & Juge, N. (2023) · FEMS Microbiology Reviews · doi:10.1093/femsre/fuad014 · Cited by 335 · see citing works
The gut microbiota-immune-brain axis: therapeutic implications
O’Riordan, K. J., Moloney, G. M., Keane, L., Clarke, G., & Cryan, J. F. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.101982 · Cited by 333 · see citing works
Ma, Z., Zuo, T., Frey, N., & Rangrez, A. Y. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01946-6 · Cited by 297 · see citing works
Feeding gut microbes to nourish the brain: unravelling the diet–microbiota–gut–brain axis
Schneider, E., O'Riordan, K. J., Clarke, G., & Cryan, J. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01108-6 · Cited by 258 · see citing works
“Microbial indole production from the bacterial metabolism of l-tryptophan derivatives further influences metabolic and gastrointestinal function in health and disease, including intestinal barrier integrity, inflammation and potentially even impacting host longevity 181,182 .”
Microbiota in inflammatory bowel disease: mechanisms of disease and therapeutic opportunities
Iliev, I. D., Ananthakrishnan, A. N., & Guo, C.-J. (2025) · Nature Reviews Microbiology · doi:10.1038/s41579-025-01163-0 · Cited by 249 · see citing works
“The most dominant bacterial groups in the gut are Firmicutes and Bacteroides, which together constitute approximately 90% of gut microbiota 11 , and are key producers of short-chain fatty acids (SCFAs) 12 .”
Neutrophils: from IBD to the gut microbiota
Danne, C., Skerniškytė, J., Marteyn, B., & Sokol, H. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00871-3 · Cited by 238 · see citing works
“Indeed, in addition to differences in intestinal microbial species and diversity, patients with IBD and healthy individuals present differences in microbial metabolism pathways 104 .”
Self-citationLü, J., Jiang, Y., Wu, L., Fu, J., Du, J., Luo, Z., Guo, L., Xu, J., & Liu, Y. F. (2024) · Nature Communications · doi:10.1038/s41467-024-45473-y · Cited by 210 · see citing works
Modulation of bone remodeling by the gut microbiota: A new therapy for osteoporosis
Lyu, Z., Hu, Y., Guo, Y., & Liu, D. (2023) · Bone Research · doi:10.1038/s41413-023-00264-x · Cited by 207 · see citing works
Interactive relationships between intestinal flora and bile acids
Guo, X., Okpara, E. S., Hu, W., Yan, C., Wang, Y., Liang, Q., Chiang, J. Y. L., & Han, S. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23158343 · Cited by 206 · see citing works
Foley, M. H., O’Flaherty, S., Allen, G., Rivera, A. J., Stewart, A. K., Barrangou, R., & Theriot, C. M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2017709118 · Cited by 205 · see citing works
Foley, M. H., Walker, M. E., Stewart, A. K., O’Flaherty, S., Gentry, E. C., Patel, S., Beaty, V. V., Allen, G., Pan, M., Simpson, J. B., et al. (2023) · Nature Microbiology · doi:10.1038/s41564-023-01337-7 · Cited by 181 · see citing works
Ge, L., Liu, S., Li, S., Yang, J., Hu, G., Xu, C., & Song, W. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1016578 · Cited by 187 · see citing works
Zhang, S., Nie, Q., Sun, Y.-G., Zuo, S., Chen, C.-H., Li, S., Yang, J., Hu, J.-L., Zhou, X.-T., Yu, Y., et al. (2024) · Microbiome · doi:10.1186/s40168-024-01896-9 · Cited by 177 · see citing works
“Certain metabolites such as short-chain fatty acids (SCFAs), bile acids, and indole derivatives were found significantly changed in patients with IBD, which affect intestinal homeostasis via multiple mechanisms [9].”
BackgroundGut microbiota in overweight and obesity: crosstalk with adipose tissue
Cani, P. D., & Hul, M. V. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00867-z · Cited by 212 · see citing works
“Bile acids are produced by the liver but are highly regulated by the activity and composition of the microbiota 178,179 .”
The Gut Microbial Bile Acid Modulation and Its Relevance to Digestive Health and Diseases
Fogelson, K. A., Dorrestein, P. C., Zarrinpar, A., & Knight, R. (2023) · Gastroenterology · doi:10.1053/j.gastro.2023.02.022 · Cited by 177 · see citing works
Recipient factors in faecal microbiota transplantation: one stool does not fit all
Danne, C., Rolhion, N., & Sokol, H. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00441-5 · Cited by 154 · see citing works
Self-citationThe Detrimental Impact of Ultra-Processed Foods on the Human Gut Microbiome and Gut Barrier
Rondinella, D., Raoul, P., Valeriani, E., Venturini, I., Cintoni, M., Severino, A., Galli, F. S., Mora, V., Mele, M. C., Cammarota, G., et al. (2025) · Nutrients · doi:10.3390/nu17050859 · Cited by 153 · see citing works
“Notably, in IBD patients, three main pathways are affected: SCFA production [106], bile acid metabolism [53], and tryptophan metabolism [54].”
The role of gut microbiota in intestinal disease: from an oxidative stress perspective
Sun, Y., Wang, X., Li, L., Zhong, C., Zhang, Y., Yang, X., Li, M., & Yang, C. (2024) · Frontiers in Microbiology · doi:10.3389/fmicb.2024.1328324 · Cited by 130 · see citing works
Hayase, E., & Jenq, R. R. (2021) · Genome Medicine · doi:10.1186/s13073-021-00923-w · Cited by 145 · see citing works
Balasubramanian, R., Schneider, E., Gunnigle, E., Cotter, P. D., & Cryan, J. F. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105562 · Cited by 136 · see citing works
“Microbial metabolites are capable of regulating the immune system (Lavelle and Sokol, 2020) via systemic circulation (Colombo et al., 2021) or by the vagus nerve (Bluthe et al., 1996; Namgung et al., 2022; Huffman et al., 2019).”
Gao, H., Sun, M., Ai, L., Gu, Q., Kang, D., Feng, Z., Li, X., Wang, X., Chen, L., Hong, Y., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2467235 · Cited by 113 · see citing works
Zhong, S., Sun, Y.-Q., Huo, J.-X., Xu, W., Yang, Y.-N., Yang, J.-B., Wu, W.-J., Liu, Y.-X., Wu, C.-M., & Li, Y.-G. (2024) · iMeta · doi:10.1002/imt2.180 · Cited by 109 · see citing works
“Compelling evidence has demonstrated the intricate connection between the gut microbiota and its metabolites and the development and progression of IBD [5, 9, 30].”
BackgroundPan, R.-Y., Zhang, J., Wang, J., Wang, Y., Li, Z., Liao, Y., Liao, Y., Zhang, C., Liu, Z., Song, L., et al. (2022) · Nature Aging · doi:10.1038/s43587-022-00311-y · Cited by 107 · see citing works
Li, M., Han, X., Sun, L.-J., Liu, X.-J., Zhang, W., & Hao, J.-Y. (2024) · Gut microbes · doi:10.1080/19490976.2024.2329147 · Cited by 104 · see citing works
“10 Indole metabolites can bind and activate the aryl hydrocarbon receptor (AhR), which induces the expression of downstream cytokines to maintain gut homeostasis.”
BackgroundMethodLi, Z.-Y., Lin, L.-H., Liang, H., Li, Y., Zhao, F., Sun, T., Liu, Z., Zhu, J., Gu, F., Xu, J.-N., et al. (2023) · Annals of Medicine · doi:10.1080/07853890.2023.2290213 · Cited by 103 · see citing works
Bile acids activated receptors in inflammatory bowel disease
Biagioli, M., Marchianò, S., Carino, A., Di Giorgio, C., Santucci, L., Distrutti, E., & Fiorucci, S. (2021) · Cells · doi:10.3390/cells10061281 · Cited by 103 · see citing works
Peng, K., Xiao, S., Xia, S., Li, C.-L., Yu, H., & Yu, Q. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c04456 · Cited by 106 · see citing works
Potential roles of gut microbiota and microbial metabolites in Parkinson’s disease
Zheng, S.-Y., Li, H.-X., Xu, R.-C., Miao, W.-T., Dai, M.-Y., Ding, S.-T., & Liu, H.-D. (2021) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101347 · Cited by 101 · see citing works
Vila, A. V., Zhang, J., Liu, M., Faber, K. N., & Weersma, R. K. (2024) · Gut · doi:10.1136/gutjnl-2023-329969 · Cited by 109 · see citing works
“Alterations of other well-studied metabolites in IBD, for example, BAs and SCFAs, 44 have also been reported in several other conditions.”
Bahman, F., Choudhry, K., Al‐Rashed, F., Al‐Mulla, F., Sindhu, S. T. A. K., & Ahmad, R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1421346 · Cited by 98 · see citing works
End-to-end design of ingestible electronics
Abdigazy, A., Arfan, M., Lazzi, G., Sideris, C., Abramson, A., & Khan, Y. (2024) · Nature Electronics · doi:10.1038/s41928-024-01122-2 · Cited by 94 · see citing works
“A variety of biomarkers present in the GI tract, such as bacteria 22 , metabolites 23 , physiological gases 24 , proteins 25 and neurotransmitters 26 , can be sensed and leveraged to assess a patient’s health in real time.”
The emerging roles of bacterial proteases in intestinal diseases
Caminero, A., Guzman, M., Libertucci, J., & Lomax, A. E. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2181922 · Cited by 92 · see citing works
Agolino, G., Pino, A., Vaccalluzzo, A., Cristofolini, M., Solieri, L., Caggia, C., & Randazzo, C. L. (2024) · Journal of Functional Foods · doi:10.1016/j.jff.2024.106357 · Cited by 87 · see citing works
Zhou, J.-X., Yang, Q.-X., Wei, W.-F., Huo, J.-H., & Wang, W.-M. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.118928 · Cited by 84
Microbiota-derived bile acids antagonize the host androgen receptor and drive anti-tumor immunity
Jin, W., Xiao, L., Jeong, M., Han, S.-J., Zhang, W., Yano, H., Shi, H., Arifuzzaman, M., Lyu, M., Wang, D., et al. (2025) · Cell · doi:10.1016/j.cell.2025.02.029 · Cited by 83 · see citing works
Integrating multi-omics to unravel host-microbiome interactions in inflammatory bowel disease
Zhang, Y., Thomas, J. P., Korcsmaros, T. D., & Gul, L. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101738 · Cited by 87 · see citing works
Touch, S., Godefroy, E., Rolhion, N., Danne, C., Oeuvray, C., Straube, M., Galbert, C., Brot, L., Alonso Salgueiro, I., Chadi, S., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.154722 · Cited by 80 · see citing works
Self-citationLiang, G., Cao, W., Tang, D., Zhang, H., Yu, Y., Ding, J., Karges, J., & Xiao, H. (2024) · ACS Nano · doi:10.1021/acsnano.3c11154 · Cited by 88 · see citing works
Microbiota-Derived Short-Chain Fatty Acids Promote LAMTOR2-Mediated Immune Responses in Macrophages
Wu, T., Li, H., Su, C., Xu, F., Yang, G., Sun, K., Xu, M., Lv, N., Meng, B., Liu, Y., et al. (2020) · mSystems · doi:10.1128/msystems.00587-20 · Cited by 78 · see citing works
Jing, W., Dong, S.-J., Xu, Y., Liu, J.-J., Ren, J.-W., Liu, X., Zhu, M., Zhang, M., Shi, H., Li, N., et al. (2024) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2024.11.009 · Cited by 77 · see citing works
Inflammatory bowel diseases: pathological mechanisms and therapeutic perspectives
Yang, X.-N., Guo, H., & Zou, M. (2026) · Molecular Biomedicine · doi:10.1186/s43556-025-00395-z · Cited by 75 · see citing works
Zhou, P., Sun, Q., Huang, L., Xia, Y., Wang, J., Mo, D.-Z., Butch, C. J., Li, C., Zhang, L., Gao, X.-J., et al. (2025) · ACS Nano · doi:10.1021/acsnano.5c08999 · Cited by 74 · see citing works
Wan, L., Qian, C., Yang, C., Peng, S.-N., Dong, G., Cheng, P., Zong, G.-F., Han, H.-K., Shao, M.-Y., Gong, G.-W., et al. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.130822 · Cited by 74 · see citing works
Chen, Z.-H., Chen, H., Huang, W., Guo, X., Yu, L., Shan, J., Deng, X., Liu, J., Li, W., Shen, W., et al. (2024) · Gut microbes · doi:10.1080/19490976.2024.2379566 · Cited by 70 · see citing works
“8,9 10–12 Bile acid metabolism is also involved in the pathogenic process of NEC and a significant elevation of total bile acid (BA) levels is observed in patients with NEC.”
BackgroundLi, J., Song, J., Deng, Z.-C., Yang, J., Wang, X.-Q., Gao, B.-W., Zhu, Y.-Y., Yang, M., Long, D.-P., Luo, X., et al. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.02.033 · Cited by 70 · see citing works
“It involves genetic risk, lifestyle factors, environmental factors, mucosal barrier dysfunction, immune dysregulation, and microbial dysregulation [6,38].”
BackgroundLi, N., Ma, P.-G., Li, Y., Shang, X., Nan, X., Shi, L., Han, X., Liu, J., Hong, Y., Li, Q., et al. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2290315 · Cited by 74 · see citing works
“11 The rest can be bio-trans-formed into secondary BAs (SBAs) by 7α-dehydrox-ylation in some members of Clostridial and Bacteroidaceae species to exert diverse metabolic effects and regulate innate and adaptive immunity.”
BackgroundResultInfluentialLei, W., Cheng, Y., Liu, X., Gao, J., Zhu, Z., Ding, W., Xu, X., Li, Y., Ling, Z., Jiang, R., et al. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1582119 · Cited by 68 · see citing works
Tong, Y., Guo, H., Abbas, Z., Zhang, J., Wang, J., Cheng, Q., Peng, S., Yang, T., Bai, T., Zhou, Y., et al. (2023) · Frontiers in Microbiology · doi:10.3389/fmicb.2023.1229952 · Cited by 70 · see citing works
Gut microbiota in regulatory T cell generation and function: mechanisms and health implications
Sharma, A., Sharma, G., & Im, S. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2516702 · Cited by 65 · see citing works
“6,32,131,132 Additionally, the distribution and expression patterns of SCFA receptors differ between mice and humans, potentially affecting downstream signaling pathways.”
Zhu, Y., Fang, Z., Bai, J., Wang, L., Chen, J.-Q., Zhang, Z.-H., Wang, Q., Sheng, W.-W., Pan, X.-Y., Gao, Z., et al. (2025) · Advancement of science · doi:10.1002/advs.202411939 · Cited by 64
Lin, X., Xu, M., Lan, R., Hu, D., Zhang, S.-P., Zhang, S.-W., Lu, Y., Sun, H., Yang, J., Liu, L.-Y., et al. (2025) · mSystems · doi:10.1128/msystems.01607-24 · Cited by 61 · see citing works
“SCFAs can reshape the gut ecology, induce immune modulation, and mediate inflammatory signaling cascade during gut inflammation (35).”
Metabolic modeling reveals a multi-level deregulation of host-microbiome metabolic networks in IBD
Taubenheim, J., Kadibalban, A. S., Zimmermann, J., Taubenheim, C., Tran, F., Schreiber, S., Rosenstiel, P., Aden, K., & Kaleta, C. (2024) · bioRxiv · doi:10.1038/s41467-025-60233-2 · Cited by 61 · see citing works
Zhu, Y.-Y., Huang, X.-L., Deng, Z.-C., Bai, T., Gao, B.-W., Xu, C.-X., Fu, J.-L., Zhao, Y., Zhang, Y.-J., Zhang, M.-X., et al. (2024) · Journal of Nanobiotechnology · doi:10.1186/s12951-024-02802-z · Cited by 61 · see citing works
“…** P 0.01, and ns represents no statistical difference microbiota can directly convert aromatic amino acids into indole derivatives, which can maintain intestinal homeostasis by promoting epithelial cell recovery, restoring intestinal barrier function, and modulating immune cell function [43–46].”
BackgroundInfluentialIqbal, M., Yu, Q., Tang, J.-Q., & Xiang, J.-J. (2025) · Journal of Bacteriology · doi:10.1128/jb.00479-24 · Cited by 60 · see citing works
“The liver synthesizes primary bile acids, such as cholic acid and chenodeoxycholic acid (CDCA) in humans, conjugating them with glycine or taurine before storing them in the gallbladder (77–79).”
Fang, X.-Y., Liu, H.-Y., Liu, J., Du, Y., Chi, Z., Bian, Y.-Q., Zhao, X., Teng, T., & Shi, B.-M. (2025) · Research · doi:10.34133/research.0673 · Cited by 60 · see citing works
“SCFA levels in the feces of patients with IBD are reduced, and the administration of butyrate can alter disease status [ 24 , 25 ].”
Chen, Y., Shui, M., Li, H., Guo, M., Yuan, Q., Hao, W., Wang, T., Zhou, H., Chen, Z., & Wang, S. (2025) · Biomaterials · doi:10.1016/j.biomaterials.2025.123163 · Cited by 61 · see citing works
Pharmacological effects of ginseng and ginsenosides on intestinal inflammation and the immune system
Zhao, L., Zhang, T., & Zhang, K. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1353614 · Cited by 60 · see citing works
Wu, S.-M., Fang, X.-Y., Zhao, J.-F., Liu, G., & Liao, P. (2025) · Toxicon · doi:10.1016/j.toxicon.2025.108434 · Cited by 58 · see citing works
Jadhav, A., Jagtap, S., Vyavahare, S., Sharbidre, A. A., & Kunchiraman, B. N. (2023) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1268041 · Cited by 70 · see citing works
Unveiling roles of beneficial gut bacteria and optimal diets for health
Kumar, S., Mukherjee, R., Gaur, P., Leal, É., Lyu, X., Ahmad, S., Puri, P., Chang, C.-M., Raj, V., & Pandey, R. (2025) · Frontiers in Microbiology · doi:10.3389/fmicb.2025.1527755 · Cited by 57 · see citing works
“Several studies have focused on elucidating the specific functions and mechanisms of these microorganisms in relation to various diseases (Lavelle and Sokol, 2020; Parada Venegas et al., 2019; Liu et al., 2022).”
Precision microbiota therapy for IBD: premise and promise
Nagayama, M., Gogokhia, L., & Longman, R. S. (2025) · Gut microbes · doi:10.1080/19490976.2025.2489067 · Cited by 56 · see citing works
“Several studies showing a distinct metabolome exists following FMT 21,54 highlight several classes of molecules that need better definition.”
Yarahmadi, A., Afkhami, H., Javadi, A., & Kashfi, M. (2024) · Diabetology & Metabolic Syndrome · doi:10.1186/s13098-024-01561-z · Cited by 59 · see citing works
“These AhRs function as vital transcription factors, assuming pivotal responsibilities in safeguarding and mitigating inflammation, notably through regulating natural lym-phoids and IL-22 within the GI tract [104, 193, 196].”
Jiang, L., Hao, Y., Han, D.-D., Dong, W.-J., Yang, A.-Y., Sun, Z.-Y., Ge, Y., Duan, S., Zhang, X., & Dai, Z.-L. (2024) · The ISME Journal · doi:10.1093/ismejo/wrae166 · Cited by 56 · see citing works
“Additionally, the gut microbiome and associated metabolites are implicated in the prevention and treatment of IBD and colorectal cancer (CRC) [11]; however, their interactions with Abx require further investigation.”
Li, X., Chen, Y., Peng, X., Zhu, Y., Duan, W., Ji, R.-Y., Xiao, H., Li, X.-L., Liu, G., Yu, Y., et al. (2024) · Food Chemistry · doi:10.1016/j.foodchem.2024.140346 · Cited by 55
Sun, H., Shu, J., Tang, J., Li, Y., Qiu, J., Ding, Z., Xuan, B., Chen, M., Gan, C., Lin, J., et al. (2024) · Immunology · doi:10.1111/imm.13784 · Cited by 54 · see citing works
“A recent study showed that GLP-1 [28 – 36], a neutral endopeptidase-generated metabolite of GLP-1, acts directly on mice through micropinocytosis [45].”
BackgroundResultInfluentialCrosstalk between gut microbiotas and fatty acid metabolism in colorectal cancer
Zhang, H., Tian, Y., Xu, C., Chen, M., Xiang, Z., Gu, L., Xue, H., & Xu, Q. R. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02364-5 · Cited by 52 · see citing works
Metabolic network of the gut microbiota in inflammatory bowel disease
Sugihara, K., & Kamada, N. (2024) · Inflammation and Regeneration · doi:10.1186/s41232-024-00321-w · Cited by 54 · see citing works
“This symbiotic relationship between gut microbiota and the host plays a vital role in maintaining intestinal homeostasis [8, 9].”
BackgroundQi, C.-L., He, G.-Y., Qian, K., Guan, S.-Y., Li, Z., Liang, S., Liu, J., Ke, X.-Z., Zhang, S.-N., Lu, M., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1002 · Cited by 52 · see citing works
Gut microbiota and epigenetic inheritance: implications for the development of IBD
Guo, X., Li, J.-H., Xu, J., Zhang, L., Huang, C., Nie, Y., & Zhou, Y.-L. (2025) · Gut microbes · doi:10.1080/19490976.2025.2490207 · Cited by 50 · see citing works
“9 In recent years, advancements in metagenomics and metabolomics technology 8,10 have substantiated the health-promoting efficacy of probiotics, correlating it with specific genes or individual nucleotides; however, the precise control mechanisms remain inade-quately understood.”
Chen, P., Rehman, M. U., He, Y., Li, A., Jian, F.-C., Zhang, L.-X., & Huang, S.-C. (2025) · Veterinary Quarterly · doi:10.1080/01652176.2025.2452169 · Cited by 50 · see citing works
Yin, Y., Li, Z., Gao, H., Zhou, D., Zhu, Z., Tao, L., Guan, W.-X., Gao, Y.-F., Song, Y.-J., & Wang, M. (2024) · Nano letters (Print) · doi:10.1021/acs.nanolett.3c03580 · Cited by 49 · see citing works
Wang, L., Zheng, W.-Y., Men, Q.-Y., Ren, X.-M., Song, S., & Ai, C. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.136687 · Cited by 48 · see citing works
Zhu, X., Zhang, C., Feng, S., He, R., & Zhang, S. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-024-01304-4 · Cited by 46 · see citing works
“…biotransformation of BA that pass through the enterohepatic circulation, which plays an important role in regulating intestinal inflammation by regulating immune cell maturation and cytokine release through farnesoid X receptor (FXR) and G protein-coupled receptor 5 (TGR5) receptors [117, 118].”
BackgroundTruyens, M., Lobatón, T., Ferrante, M., Bossuyt, P., Vermeire, S., Pouillon, L., Dewint, P., Cremer, A., Peeters, H., Lambrecht, G., et al. (2022) · Gastroenterology · doi:10.1053/j.gastro.2022.07.052 · Cited by 48 · see citing works
Wang, Q., Huang, H., Yang, Y., Yang, X.-L., Li, X.-M., Zhong, W., Wen, B., He, F., & Li, J. (2024) · Frontiers in Nutrition · doi:10.3389/fnut.2024.1491821 · Cited by 47 · see citing works
“In both mouse models and IBD patients, dietary tryptophan deficiency exacerbates colitis (160).”
BackgroundGut Microbiome as a Target of Intervention in Inflammatory Bowel Disease Pathogenesis and Therapy
Hetta, . F., Ramadan, Y. N., Alharbi, A. A., Alsharif, S. M., Alkindy, T. T., Alkhamali, A., Albalawi, A. S., & El‐Amin, H. (2024) · Immuno · doi:10.3390/immuno4040026 · Cited by 50 · see citing works
“However, some phages actively integrate their genetic element into the infected cells’ genomes, transmitting this information to the next generation of host cells (lysogenic cycle) [126,127].”
BackgroundJiang, S., Ma, W., Ma, C., Zhang, Z., Zhang, W., & Zhang, J. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2341717 · Cited by 52 · see citing works
“…function, and inflammation, which makes it harder to fight pathogens, 22 thereby inducing various diseases, such as inflammatory bowel diseases; 23,24 metabolic disorders, such as obesity and type 2 diabetes; 25–27 autoimmune diseases, 28,29 such as food allergies, 30 eczema, 31 and asthma; 32…”
BackgroundXing, L.-Y., Liu, X., Wu, L., Wu, J., Deng, Y., Li, Q.-Y., Zhou, Z., Li, L., & Huang, Y. (2024) · Nano Today · doi:10.1016/j.nantod.2024.102155 · Cited by 47 · see citing works
Epithelial regulation of microbiota-immune cell dynamics
Didriksen, B. J., Eshleman, E. M., & Alenghat, T. (2024) · Mucosal Immunology · doi:10.1016/j.mucimm.2024.02.008 · Cited by 47 · see citing works
Aromatic Amino Acid Metabolites: Molecular Messengers Bridging Immune-Microbiota Communication
Shin, H., & Bang, Y.-J. (2025) · Immune Network · doi:10.4110/in.2025.25.e10 · Cited by 46 · see citing works
“These microorganisms produce various bioactive metabolites that act as essential mediators in host-microbe communication, influencing both local and systemic immune responses (1,2).”
Yuan, M., Chang, L., Gao, P., Li, J., Xin-yuan, L., Hua, M., Li, X., Liu, X., & Lan, Y. (2024) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2024.133794 · Cited by 50 · see citing works
Inhibiting the cGAS-STING Pathway in Ulcerative Colitis with Programmable Micelles.
Uthaman, S., Parvinroo, S., Mathew, A., Jia, X., Hernandez, B. G., Proctor, A., Sajeevan, K. A., Nenninger, A. S., Long, M., Park, I.-K., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c11257 · Cited by 46 · see citing works
Wang, Y., Zhou, Y.-H., Wu, Q.-Y., Li, Y.-S., Huang, Y.-L., Yu, K., Li, P., Lv, Z., Liu, H.-T., Zou, H., et al. (2025) · Advancement of science · doi:10.1002/advs.202505208 · Cited by 45 · see citing works
Wang, C., Gu, Y., Chu, Q., Wang, X., Ding, Y.-Y., Qin, X., Liu, T.-Y., Wang, S.-N., Liu, X., Wang, B.-M., et al. (2024) · Microbiology Research · doi:10.1016/j.micres.2024.127660 · Cited by 45 · see citing works
Cao, J., Bao, Q.-Y., & Hao, H. (2024) · Antioxidants · doi:10.3390/antiox13091107 · Cited by 44 · see citing works
“Metabolites derived from gut microbiota are key signaling molecules that mediate the interaction between gut microbiota and the host, playing an important role in regulating the body’s immune and inflammatory responses [39].”
BackgroundYang, Y., Li, N., Gao, Y.-B., Xu, F., Chen, H., Zhang, C., & Ni, X.-L. (2024) · BMC Microbiology · doi:10.1186/s12866-024-03217-4 · Cited by 44 · see citing works
“It plays an essential role in human digestion, metabolism, immunity, and other processes and is closely connected with the health of the host [30].”
BackgroundGut bacteria Prevotellaceae related lithocholic acid metabolism promotes colonic inflammation
Chen, L.-P., Ye, Z.-H., Li, J.-H., Wang, L., Chen, Y., Yu, M., Han, J., Huang, J., Li, D.-Y., Lv, Y., et al. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-024-05873-6 · Cited by 43 · see citing works
“Research has demonstrated gut microbiota-related metabolites are closely linked to colonic inflammation [8].”
Chen, Y., Chen, S.-Y., Chang, H., Liu, Y.-C., Chuang, B.-F., & Yen, G. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.129043 · Cited by 38 · see citing works
Caldarelli, M., Rio, P., Marrone, A., Giambra, V., Gasbarrini, A., Gambassi, G., & Cianci, R. (2024) · Biomedicines · doi:10.3390/biomedicines12081716 · Cited by 42 · see citing works
Zhang, Y., Han, L., Dong, J.-Q., Yuan, Z.-W., Yao, W.-L., Ji, P., Hua, Y.-L., & Wei, Y.-M. (2024) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2024.117874 · Cited by 42 · see citing works
Luo, K.-C., Zhang, M.-T., Tu, Q.-W., Li, J., Wang, Y., Wan, S.-L., Li, D.-J., Qian, Q., & Xia, L. (2025) · Journal of Neuroinflammation · doi:10.1186/s12974-025-03476-6 · Cited by 41 · see citing works
“Other microbial metabolites, such as tryptophan and glycine, have been reported to be closely associated with comorbid anxiety and depression in individuals with IBD, but the underlying mechanisms require further exploration [89–92].”
Integrating multi-omics data to reveal the host-microbiota interactome in inflammatory bowel disease
Su, F., Su, M., Wei, W., Wu, J., Chen, L., Sun, X., Liu, M., Sun, S., Mao, R., Bourgonje, A. R., et al. (2025) · Gut Microbes · doi:10.1080/19490976.2025.2476570 · Cited by 42 · see citing works
“69 In patients with active IBD, fecal levels of conjugated (primary) BAs are significantly elevated, while levels of secondary BAs are markedly decreased.”
Zong, G.-F., Deng, R., Pan, Y.-H., Liu, M., Zhu, H.-Z., Tao, R.-Z., Shan, Y.-L., Wei, Z.-H., & Lu, Y. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.142015 · Cited by 41 · see citing works
Häcker, D., Siebert, K., Smith, B. J., Koehler, N., Riva, A., Mahapatra, A., Heimes, H., Nie, J., Metwaly, A., Hölz, H., et al. (2024) · Cell Host and Microbe · doi:10.1016/j.chom.2024.10.001 · Cited by 41 · see citing works
“12 15 Despite recent findings that EEN mediates protective functions in experimental models of colitis, 16 human studies revealed incomplete recovery of the intestinal microbiome after antibiotic interventions.”
Li, J.-K., Veeraperumal, S., Aweya, J., Liu, Y., & Cheong, K. (2024) · Carbohydrate Polymers · doi:10.1016/j.carbpol.2024.122421 · Cited by 41 · see citing works
Liu, Y., Bai, X., Wu, H., Duan, Z., Zhu, C., Fu, R., & Fan, D. (2024) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.4c00245 · Cited by 42 · see citing works
Toward improved <i>in vitro</i> models of human cancer
Ayuso, J. M., Park, K.-Y., Virumbrales-Muñoz, M., & Beebe, D. J. (2021) · APL Bioengineering · doi:10.1063/5.0026857 · Cited by 40 · see citing works
Lipids in Clinical Nutrition and Health: Narrative Review and Dietary Recommendations
Frydrych, A., Kulita, K., Jurowski, K., & Piekoszewski, W. (2025) · Foods · doi:10.3390/foods14030473 · Cited by 47 · see citing works
“SCFAs are very important metabolites, affecting the modulation of the immune system, and as a result, their dysfunction is associated with inflammatory bowel diseases [85].”
- Authors
- Lavelle, A., & Sokol, H.
- Affiliations
- Inserm (FR)
- Corresponding author
- Sokol, Harry
- Venue
- Nature Reviews Gastroenterology & Hepatology
- Published
- 2020-02-19
- Volume
- 17
- Issue
- 4
- Pages
- 223-237
- ISSN
- 1759-5045 (ISSN-L)
- 1759-5053
- 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
- Locations
- Nature Reviews Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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 ›
Are you an author, or do you see a problem with this page? Request a review
