GUT MICROBIOTA AS A KEY MODULATOR OF METABOLIC SYNDROME AND OBESITY: MECHANISMS, CLINICAL EVIDENCE, AND THERAPEUTIC PERSPECTIVES
DOI:
https://doi.org/10.31435/ijitss.2(50).2026.5108Keywords:
Gut Microbiota, Obesity, Metabolic Syndrome, Dysbiosis, Short-Chain Fatty Acids, InflammationAbstract
The global escalation of obesity and metabolic syndrome (MetS) represents a significant challenge to public health systems (World Health Organization, 2024). Emerging evidence identifies the gut microbiota—the complex community of microorganisms inhabiting the gastrointestinal tract—as a critical environmental factor influencing host energy homeostasis and inflammation (Evans et al., 2013). This review examines the intricate mechanisms through which gut dysbiosis contributes to the pathogenesis of obesity and MetS, including altered energy extraction, modulation of lipid metabolism, and the induction of chronic low-grade inflammation via metabolic endotoxemia (Cani et al., 2007). We synthesize current clinical evidence from human cohort studies that correlate specific microbial signatures with metabolic health (Le Chatelier et al., 2013). Furthermore, this article explores therapeutic perspectives, evaluating the efficacy of probiotics, prebiotics, and fecal microbiota transplantation (FMT) in restoring metabolic balance (Vrieze et al., 2012). A core focus is placed on the integration of advanced bioinformatic frameworks, such as the QIIME 2 pipeline and Random Forest machine learning architectures, which facilitate the transition from taxonomic description to functional, predictive modeling of the gut-metabolic axis (Knight et al., 2018; Zeevi et al., 2015). By integrating findings from molecular biology, systems engineering, and clinical trials, we conclude that the gut microbiota is a viable target for personalized therapeutic interventions in metabolic diseases (Fan & Pedersen, 2021).
References
Alberti, K. G., Eckel, R. H., Grundy, S. M., Zimmet, P. Z., Cleeman, J. I., Donato, K. A., Fruchart, J. C., James, W. P., Loria, C. M., Smith, S. C., Jr., International Diabetes Federation Task Force on Epidemiology and Prevention, National Heart, Lung, and Blood Institute, American Heart Association, World Heart Federation, International Atherosclerosis Society, & International Association for the Study of Obesity. (2009). Harmonizing the metabolic syndrome: A joint interim statement. Circulation, 120(16), 1640–1645. https://doi.org/10.1161/CIRCULATIONAHA.109.192644
Bäckhed, F., Ding, H., Wang, T., Hooper, L. V., Koh, G. Y., Nagy, A., Semenkovich, C. F., & Gordon, J. I. (2004). The gut microbiota as an environmental factor that regulates fat storage. Proceedings of the National Academy of Sciences of the United States of America, 101(44), 15718–15723. https://doi.org/10.1073/pnas.0407076101
Borody, T. J., & Khoruts, A. (2011). Fecal microbiota transplantation and emerging applications. Nature Reviews Gastroenterology & Hepatology, 9(2), 88–96. https://doi.org/10.1038/nrgastro.2011.244
Bouter, K. E., van Raalte, D. H., Groen, A. K., & Nieuwdorp, M. (2017). Role of the gut microbiome in the pathogenesis of obesity and obesity-related metabolic dysfunction. Gastroenterology, 152(7), 1671–1678. https://doi.org/10.1053/j.gastro.2016.12.048
Cani, P. D., & Jordan, B. F. (2018). Gut microbiota-mediated inflammation in obesity: A link with gastrointestinal cancer. Nature Reviews Gastroenterology & Hepatology, 15(11), 671–682. https://doi.org/10.1038/s41575-018-0025-6
Cani, P. D. (2018). Human gut microbiome: Hopes, threats and promises. Gut, 67(9), 1716–1725. https://doi.org/10.1136/gutjnl-2018-316723
Cani, P. D., Amar, J., Iglesias, M. A., Poggi, M., Knauf, C., Bastelica, D., Neyrinck, A. M., Fava, F., Tuohy, K. M., Chabo, C., Waget, A., Delmée, E., Cousin, B., Sulpice, T., Chamontin, B., Ferrières, J., Tanti, J. F., Gibson, G. R., Casteilla, L., Delzenne, N. M., … Burcelin, R. (2007). Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes, 56(7), 1761–1772. https://doi.org/10.2337/db06-1491
Cani, P. D., Bibiloni, R., Knauf, C., Waget, A., Neyrinck, A. M., Delzenne, N. M., & Burcelin, R. (2008). Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes, 57(6), 1470–1481. https://doi.org/10.2337/db07-1403
Cani, P. D., Osto, M., Geurts, L., & Everard, A. (2012). Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity. Gut Microbes, 3(4), 279–288. https://doi.org/10.4161/gmic.19625
Cryan, J. F., & Dinan, T. G. (2012). Mind-altering microorganisms: The impact of the gut microbiota on brain and behaviour. Nature Reviews Neuroscience, 13(10), 701–712. https://doi.org/10.1038/nrn3346
Depommier, C., Everard, A., Druart, C., Plovier, H., Van Hul, M., Vieira-Silva, S., Falony, G., Raes, J., Maiter, D., Delzenne, N. M., de Barsy, M., Loumaye, A., Hermans, M. P., Thissen, J. P., de Vos, W. M., & Cani, P. D. (2019). Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: A proof-of-concept exploratory study. Nature Medicine, 25(7), 1096–1103. https://doi.org/10.1038/s41591-019-0495-2
Evans, J. M., Morris, L. S., & Marchesi, J. R. (2013). The gut microbiome: The role of a virtual organ in the endocrinology of the host. The Journal of Endocrinology, 218(3), R37–R47. https://doi.org/10.1530/JOE-13-0131
Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J. P., Druart, C., Bindels, L. B., Guiot, Y., Derrien, M., Muccioli, G. G., Delzenne, N. M., de Vos, W. M., & Cani, P. D. (2013). Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proceedings of the National Academy of Sciences of the United States of America, 110(22), 9066–9071. https://doi.org/10.1073/pnas.1219451110
Frost, G., Sleeth, M. L., Sahuri-Arisoylu, M., Lizarbe, B., Cerdan, S., Brody, L., Anastasovska, J., Ghourab, S., Hankir, M., Zhang, S., Carling, D., Swann, J. R., Gibson, G., Viardot, A., Morrison, D., Louise Thomas, E., & Bell, J. D. (2014). The short-chain fatty acid acetate reduces appetite via a central homeostatic mechanism. Nature Communications, 5, 3611. https://doi.org/10.1038/ncomms4611
Gibson, G. R., Hutkins, R., Sanders, M. E., Prescott, S. L., Reimer, R. A., Salminen, S. J., Scott, K., Stanton, C., Swanson, K. S., Cani, P. D., Verbeke, K., & Reid, G. (2017). Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the definition and scope of prebiotics. Nature Reviews Gastroenterology & Hepatology, 14(8), 491–502. https://doi.org/10.1038/nrgastro.2017.75
Hotamisligil, G. S. (2006). Inflammation and metabolic disorders. Nature, 444(7121), 860–867. https://doi.org/10.1038/nature05485
Karlsson, F. H., Tremaroli, V., Nookaew, I., Bergström, G., Behre, C. J., Fagerberg, B., Nielsen, J., & Bäckhed, F. (2013). Gut metagenome in European women with normal, impaired and diabetic glucose control. Nature, 498(7452), 99–103. https://doi.org/10.1038/nature12198
Knight, R., Vrbanac, A., Taylor, B. C., Aksenov, A., Callewaert, C., Debelius, J., Gonzalez, A., Kosciolek, T., McCall, L. I., McDonald, D., Melnik, A. V., Morton, J. T., Navas, J., Quinn, R. A., Sanders, J. G., Swafford, A. D., Thompson, L. R., Tripathi, A., Xu, Z. Z., Zaneveld, J. R., … Dorrestein, P. C. (2018). Best practices for analysing microbiomes. Nature Reviews Microbiology, 16(7), 410–422. https://doi.org/10.1038/s41579-018-0029-9
Kootte, R. S., Levin, E., Salojärvi, J., Smits, L. P., Hartstra, A. V., Udayappan, S. D., Hermes, G., Bouter, K. E., Koopen, A. M., Holst, J. J., Knop, F. K., Blaak, E. E., Zhao, J., Smidt, H., Harms, A. C., Hankemeijer, T., Bergman, J. J. G. H. M., Romijn, H. A., Schaap, F. G., Olde Damink, S. W. M., … Nieuwdorp, M. (2017). Improvement of insulin sensitivity after lean donor feces in metabolic syndrome is driven by baseline intestinal microbiota composition. Cell Metabolism, 26(4), 611–619.e6. https://doi.org/10.1016/j.cmet.2017.09.008
Chow, M. D., Lee, Y. H., & Guo, G. L. (2017). The role of bile acids in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis. Molecular Aspects of Medicine, 56, 34–44. https://doi.org/10.1016/j.mam.2017.04.004
Le Chatelier, E., Nielsen, T., Qin, J., Prifti, E., Hildebrand, F., Falony, G., Almeida, M., Arumugam, M., Batto, J. M., Kennedy, S., Leonard, P., Li, J., Burgdorf, K., Grarup, N., Jørgensen, T., Brandslund, I., Nielsen, H. B., Juncker, A. S., Bertalan, M., Levenez, F., … Pedersen, O. (2013). Richness of human gut microbiome correlates with metabolic markers. Nature, 500(7464), 541–546. https://doi.org/10.1038/nature12506
Ley, R. E., Bäckhed, F., Turnbaugh, P., Lozupone, C. A., Knight, R. D., & Gordon, J. I. (2005). Obesity alters gut microbial ecology. Proceedings of the National Academy of Sciences of the United States of America, 102(31), 11070–11075. https://doi.org/10.1073/pnas.0504978102
Ley, R. E., Turnbaugh, P. J., Klein, S., & Gordon, J. I. (2006). Microbial ecology: Human gut microbes associated with obesity. Nature, 444(7122), 1022–1023. https://doi.org/10.1038/4441022a
Lin, H. V., Frassetto, A., Kowalik, E. J., Jr., Nawrocki, A. R., Lu, M. M., Kosinski, J. R., Hubert, J. A., Szeto, D., Yao, X., Forrest, G., & Marsh, D. J. (2012). Butyrate and propionate protect against diet-induced obesity and regulate gut hormones via free fatty acid receptor 3-independent mechanisms. PLOS ONE, 7(4), e35240. https://doi.org/10.1371/journal.pone.0035240
Lynch, S. V., & Pedersen, O. (2016). The human intestinal microbiome in health and disease. The New England Journal of Medicine, 375(24), 2369–2379. https://doi.org/10.1056/NEJMra1600266
Morrison, D. J., & Preston, T. (2016). Formation of short-chain fatty acids by the gut microbiota and their impact on human metabolism. Gut Microbes, 7(3), 189–200. https://doi.org/10.1080/19490976.2015.1134082
Postler, T. S., & Ghosh, S. (2017). Understanding the holobiont: How microbial metabolites affect human health and shape the immune system. Cell Metabolism, 26(1), 110–130. https://doi.org/10.1016/j.cmet.2017.05.008
Pussinen, P. J., Havulinna, A. S., Lehto, M., Sundvall, J., & Salomaa, V. (2011). Endotoxemia is associated with an increased risk of incident diabetes. Diabetes Care, 34(2), 392–397. https://doi.org/10.2337/dc10-1676
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., Peng, Y., Zhang, D., Jie, Z., Wu, W., Qin, Y., Xue, W., Li, J., Han, L., Lu, D., Wu, P., … Wang, J. (2012). A metagenome-wide association study of gut microbiota in type 2 diabetes. Nature, 490(7418), 55–60. https://doi.org/10.1038/nature11450
Queipo-Ortuño, M. I., Seoane, L. M., Murri, M., Pardo, M., Gomez-Zumaquero, J. M., Cardona, F., Casanueva, F., & Tinahones, F. J. (2013). Gut microbiota composition in male rat models under different nutritional status and physical activity and its association with serum leptin and ghrelin levels. PLOS ONE, 8(5), e65465. https://doi.org/10.1371/journal.pone.0065465
Byrne, C. S., Chambers, E. S., Morrison, D. J., & Frost, G. (2015). The role of short-chain fatty acids in appetite regulation and energy homeostasis. International Journal of Obesity, 39(9), 1331–1338. https://doi.org/10.1038/ijo.2015.84
Sanchez, M., Darimont, C., Drapeau, V., Emady-Azar, S., Lepage, M., Rezzonico, E., Ngom-Bru, C., Berger, B., Philippe, L., Ammon-Zuffrey, C., Leone, P., Chevrier, G., St-Amand, E., Marette, A., Doré, J., & Tremblay, A. (2014). Effect of Lactobacillus rhamnosus CGMCC1.3724 supplementation on weight loss and maintenance in obese men and women. The British Journal of Nutrition, 111(8), 1507–1519. https://doi.org/10.1017/S0007114513003875
Sayin, S. I., Wahlström, A., Felin, J., Jäntti, S., Marschall, H. U., Bamberg, K., Angelin, B., Hyötyläinen, T., Orešič, M., & Bäckhed, F. (2013). Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metabolism, 17(2), 225–235. https://doi.org/10.1016/j.cmet.2013.01.003
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. The Journal of Clinical Investigation, 116(11), 3015–3025. https://doi.org/10.1172/JCI28898
Sze, M. A., & Schloss, P. D. (2016). Looking for a signal in the noise: Revisiting obesity and the microbiome. mBio, 7(4), e01018-16. https://doi.org/10.1128/mBio.01018-16
Thomas, C., Gioiello, A., Noriega, L., Strehle, A., Oury, J., Rizzo, G., Macchiarulo, A., Yamamoto, H., Mataki, C., Pruzanski, M., Pellicciari, R., Auwerx, J., & Schoonjans, K. (2009). TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metabolism, 10(3), 167–177. https://doi.org/10.1016/j.cmet.2009.08.001
Turnbaugh, P. J., Ley, R. E., Mahowald, M. A., Magrini, V., Mardis, E. R., & Gordon, J. I. (2006). An obesity-associated gut microbiome with increased capacity for energy harvest. Nature, 444(7122), 1027–1031. https://doi.org/10.1038/nature05414
Turnbaugh, P. J., Hamady, M., Yatsunenko, T., Cantarel, B. L., Duncan, A., Ley, R. E., Sogin, M. L., Jones, W. J., Roe, B. A., Affourtit, J. P., Egholm, M., Henrissat, B., Heath, A. C., Knight, R., & Gordon, J. I. (2009). A core gut microbiome in obese and lean twins. Nature, 457(7228), 480–484. https://doi.org/10.1038/nature07540
Vrieze, A., Van Nood, E., Holleman, F., Salojärvi, J., Kootte, R. S., Bartelsman, J. F., Dallinga-Thie, G. M., Ackermans, M. T., Serlie, M. J., Oozeer, R., Derrien, M., Druesne, A., Van Hylckama Vlieg, J. E., Bloks, V. W., Groen, A. K., Heilig, H. G., Zoetendal, E. G., Stroes, E. S., de Vos, W. M., Hoekstra, J. B., … Nieuwdorp, M. (2012). Transfer of intestinal microbiota from lean donors increases insulin sensitivity in individuals with metabolic syndrome. Gastroenterology, 143(4), 913–916.e7. https://doi.org/10.1053/j.gastro.2012.06.031
Wahlström, A., Sayin, S. I., Marschall, H. U., & Bäckhed, F. (2016). Intestinal crosstalk between bile acids and microbiota and its impact on host metabolism. Cell Metabolism, 24(1), 41–50. https://doi.org/10.1016/j.cmet.2016.05.005
Zeevi, D., Korem, T., Zmora, N., Israeli, D., Rothschild, D., Weinberger, A., Ben-Yacov, O., Lador, D., Avnit-Sagi, T., Lotan-Pompan, M., Suez, J., Mahdi, J. A., Matot, E., Malka, G., Kosower, N., Rein, M., Zilberman-Schapira, G., Dohnalová, L., Pevsner-Fischer, M., Bikovsky, R., … Segal, E. (2015). Personalized nutrition by prediction of glycemic responses. Cell, 163(5), 1079–1094. https://doi.org/10.1016/j.cell.2015.11.001
World Health Organization. (2024, March 1). Obesity and overweight. https://www.who.int/news-room/fact-sheets/detail/obesity-and-overweight
Ridaura, V. K., Faith, J. J., Rey, F. E., Cheng, J., Duncan, A. E., Kau, A. L., Griffin, N. W., Lombard, V., Henrissat, B., Bain, J. R., Muehlbauer, M. J., Ilkayeva, O., Semenkovich, C. F., Funai, K., Hayashi, D. K., Lyle, B. J., Martini, M. C., Ursell, L. K., Clemente, J. C., Van Treuren, W., … Gordon, J. I. (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science, 341(6150), 1241214. https://doi.org/10.1126/science.1241214
Sonnenburg, J. L., & Bäckhed, F. (2016). Diet-microbiota interactions as moderators of human metabolism. Nature, 535(7610), 56–64. https://doi.org/10.1038/nature18846
Zhao, L., Zhang, F., Ding, X., Wu, G., Lam, Y. Y., Wang, X., Fu, H., Xue, X., Lu, C., Ma, J., Yu, L., Xu, C., Ren, Z., Xu, Y., Xu, S., Shen, H., Zhu, X., Shi, Y., Shen, Q., Dong, W., … Zhang, C. (2018). Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 359(6380), 1151–1156. https://doi.org/10.1126/science.aao5774
Tremaroli, V., & Bäckhed, F. (2012). Functional interactions between the gut microbiota and host metabolism. Nature, 489(7415), 242–249. https://doi.org/10.1038/nature11552
Koh, A., De Vadder, F., Kovatcheva-Datchary, P., & Bäckhed, F. (2016). From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell, 165(6), 1332–1345. https://doi.org/10.1016/j.cell.2016.05.041
Mithieux, G. (2018). Gut microbiota and host metabolism: What relationship. Neuroendocrinology, 106(4), 352–356. https://doi.org/10.1159/000484526
Fan, Y., & Pedersen, O. (2021). Gut microbiota in human metabolic health and disease. Nature Reviews Microbiology, 19(1), 55–71. https://doi.org/10.1038/s41579-020-0433-9
Maruvada, P., Leone, V., Kaplan, L. M., & Chang, E. B. (2017). The human microbiome and obesity: Moving beyond associations. Cell Host & Microbe, 22(5), 589–599. https://doi.org/10.1016/j.chom.2017.10.005
Schroeder, B. O., & Bäckhed, F. (2016). Signals from the gut microbiota to distant organs in physiology and disease. Nature Medicine, 22(10), 1079–1089. https://doi.org/10.1038/nm.4185
Valdes, A. M., Walter, J., Segal, E., & Spector, T. D. (2018). Role of the gut microbiota in nutrition and health. BMJ, 361, k2179. https://doi.org/10.1136/bmj.k2179
Aguilar-Toalá, J. E., García-Varela, R., Garcia, H. S., Mata-Haro, V., González-Córdova, A. F., Vallejo-Cordoba, B., & Hernandez-Mendoza, A. (2018). Postbiotics: An evolving term within the functional foods field. Trends in Food Science & Technology, 75, 105–114. https://doi.org/10.1016/j.tifs.2018.03.009
Bjursell, M., Admyre, T., Göransson, M., Marley, A. E., Smith, D. M., Oscarsson, J., & Bohlooly-Y, M. (2011). Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet. American Journal of Physiology-Endocrinology and Metabolism, 300(1), E211–E220. https://doi.org/10.1152/ajpendo.00229.2010
Brown, A. J., Goldsworthy, S. M., Barnes, A. A., Eilert, M. M., Tcheang, L., Daniels, D., Muir, A. I., Wigglesworth, M. J., Kinghorn, I., Fraser, N. J., Pike, N. B., Strum, J. C., Steplewski, K. M., Murdock, P. R., Holder, J. C., Marshall, F. H., Szekeres, P. G., Wilson, S., Ignar, D. M., Foord, S. M., … Dowell, S. J. (2003). The orphan G protein-coupled receptors GPR41 and GPR43 are activated by propionate and other short chain carboxylic acids. The Journal of Biological Chemistry, 278(13), 11312–11319. https://doi.org/10.1074/jbc.M211609200
Zimmerman, M. A., Singh, N., Martin, P. M., Thangaraju, M., Ganapathy, V., Waller, J. L., Shi, H., Robertson, K. D., Munn, D. H., & Liu, K. (2012). Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells. American Journal of Physiology-Gastrointestinal and Liver Physiology, 302(12), G1405–G1415. https://doi.org/10.1152/ajpgi.00543.2011
De Vadder, F., Kovatcheva-Datchary, P., Goncalves, D., Vinera, J., Zitoun, C., Duchampt, A., Bäckhed, F., & Mithieux, G. (2014). Microbiota-generated metabolites promote metabolic benefits via gut-brain neural circuits. Cell, 156(1–2), 84–96. https://doi.org/10.1016/j.cell.2013.12.016
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., Takahashi, M., Fukuda, N. N., Murakami, S., Miyauchi, E., Hino, S., Atarashi, K., Onawa, S., Fujimura, Y., Lockett, T., Clarke, J. M., … Ohno, H. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 504(7480), 446–450. https://doi.org/10.1038/nature12721
Ge, H., Li, X., Weiszmann, J., Wang, P., Baribault, H., Chen, J. L., Tian, H., & Li, Y. (2008). Activation of G protein-coupled receptor 43 in adipocytes leads to inhibition of lipolysis and suppression of plasma free fatty acids. Endocrinology, 149(9), 4519–4526. https://doi.org/10.1210/en.2008-0059
Gomaa, A. A., Klumpe, H. E., Luo, M. L., Selle, K., Barrangou, R., & Beisel, C. L. (2014). Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems. mBio, 5(1), e00928-13. https://doi.org/10.1128/mBio.00928-13
Kalliomäki, M., Collado, M. C., Salminen, S., & Isolauri, E. (2008). Early differences in fecal microbiota composition in children may predict overweight. The American Journal of Clinical Nutrition, 87(3), 534–538. https://doi.org/10.1093/ajcn/87.3.534
Kimura, I., Inoue, D., Maeda, T., Hara, T., Ichimura, A., Miyauchi, S., Kobayashi, M., Hirasawa, A., & Tsujimoto, G. (2011). Short-chain fatty acids and ketones directly regulate sympathetic nervous system via G protein-coupled receptor 41. Proceedings of the National Academy of Sciences of the United States of America, 108(19), 8030–8035. https://doi.org/10.1073/pnas.1016088108
Kimura, I., Ozawa, K., Inoue, D., Imamura, T., Kimura, K., Maeda, T., Terasawa, K., Kashihara, D., Hirano, K., Tani, T., Takahashi, T., Miyauchi, S., Shioi, G., Inoue, H., & Tsujimoto, G. (2013). The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nature Communications, 4, 1829. https://doi.org/10.1038/ncomms2852
Macfarlane, G. T., & Macfarlane, S. (2011). Fermentation in the human large intestine: Its physiologic consequences and the potential contribution of prebiotics. Journal of Clinical Gastroenterology, 45(Suppl.), S120–S127. https://doi.org/10.1097/MCG.0b013e31822fecfe
Plovier, H., Everard, A., Druart, C., Depommier, C., Van Hul, M., Geurts, L., Chilloux, J., Ottman, N., Duparc, T., Lichtenstein, L., Myridakis, A., Delzenne, N. M., Klievink, J., Bhattacharjee, A., van der Ark, K. C., Aalvink, S., Martinez, L. O., Dumas, M. E., Maiter, D., Loumaye, A., … Cani, P. D. (2017). A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice. Nature Medicine, 23(1), 107–113. https://doi.org/10.1038/nm.4236
Samuel, B. S., Shaito, A., Motoike, T., Rey, F. E., Backhed, F., Manchester, J. K., Hammer, R. E., Williams, S. C., Crowley, J., Yanagisawa, M., & Gordon, J. I. (2008). Effects of the gut microbiota on host adiposity are modulated by the short-chain-fatty-acid binding G protein-coupled receptor Gpr41. Proceedings of the National Academy of Sciences of the United States of America, 105(43), 16767–16772. https://doi.org/10.1073/pnas.0808567105
Singh, N., Gurav, A., Sivaprakasam, S., Brady, E., Padia, R., Shi, H., Thangaraju, M., Prasad, P. D., Manicassamy, S., Munn, D. H., Lee, J. R., Offermanns, S., & Ganapathy, V. (2014). Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity, 40(1), 128–139. https://doi.org/10.1016/j.immuni.2013.12.007
Smith, P. M., Howitt, M. R., Panikov, N., Michaud, M., Gallini, C. A., Bohlooly-Y, M., Glickman, J. N., & Garrett, W. S. (2013). The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science, 341(6145), 569–573. https://doi.org/10.1126/science.1241165
Thaiss, C. A., Itav, S., Rothschild, D., Meijer, M. T., Levy, M., Moresi, C., Dohnalová, L., Braverman, S., Rozin, S., Malitsky, S., Dori-Bachash, M., Kuperman, Y., Biton, I., Gertler, A., Harmelin, A., Shapiro, H., Halpern, Z., Aharoni, A., Segal, E., & Elinav, E. (2016). Persistent microbiome alterations modulate the rate of post-dieting weight regain. Nature, 540(7634), 544–551. https://doi.org/10.1038/nature20796
Tolhurst, G., Heffron, H., Lam, Y. S., Parker, H. E., Habib, A. M., Diakogiannaki, E., Cameron, J., Grosse, J., Reimann, F., & Gribble, F. M. (2012). Short-chain fatty acids stimulate glucagon-like peptide-1 secretion via the G-protein-coupled receptor FFAR2. Diabetes, 61(2), 364–371. https://doi.org/10.2337/db11-1019
Ghoshal, S., Witta, J., Zhong, J., de Villiers, W., & Eckhardt, E. (2009). Chylomicrons promote intestinal absorption of lipopolysaccharides. Journal of Lipid Research, 50(1), 90–97. https://doi.org/10.1194/jlr.M800156-JLR200
Groschwitz, K. R., & Hogan, S. P. (2009). Intestinal barrier function: Molecular regulation and disease pathogenesis. The Journal of Allergy and Clinical Immunology, 124(1), 3–22. https://doi.org/10.1016/j.jaci.2009.05.038
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996). IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science, 271(5249), 665–668. https://doi.org/10.1126/science.271.5249.665
Muccioli, G. G., Naslain, D., Bäckhed, F., Reigstad, C. S., Lambert, D. M., Delzenne, N. M., & Cani, P. D. (2010). The endocannabinoid system links gut microbiota to adipogenesis. Molecular Systems Biology, 6, 392. https://doi.org/10.1038/msb.2010.46
Pedersen, H. K., Gudmundsdottir, V., Nielsen, H. B., Hyotylainen, T., Nielsen, T., Jensen, B. A., Forslund, K., Hildebrand, F., Prifti, E., Falony, G., Le Chatelier, E., Levenez, F., Doré, J., Mattila, I., Plichta, D. R., Pöhö, P., Hellgren, L. I., Arumugam, M., Sunagawa, S., Vieira-Silva, S., … Pedersen, O. (2016). Human gut microbes impact host serum metabolome and insulin sensitivity. Nature, 535(7612), 376–381. https://doi.org/10.1038/nature18646
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. The Journal of Clinical Investigation, 116(11), 3015–3025. https://doi.org/10.1172/JCI28898
Stenman, L. K., Lehtinen, M. J., Meland, N., Christensen, J. E., Yeung, N., Saarinen, M. T., Courtney, M., Burcelin, R., Lähdeaho, M. L., Linros, J., Apter, D., Scheinin, M., Kloster Smerud, H., Rissanen, A., & Lahtinen, S. (2016). Probiotic with or without fiber controls body fat mass, associated with serum zonulin, in overweight and obese adults: Randomized controlled trial. EBioMedicine, 13, 190–200. https://doi.org/10.1016/j.ebiom.2016.10.036
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., & Chen, H. (2003). Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. The Journal of Clinical Investigation, 112(12), 1821–1830. https://doi.org/10.1172/JCI19451
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W., Jr. (2003). Obesity is associated with macrophage accumulation in adipose tissue. The Journal of Clinical Investigation, 112(12), 1796–1808. https://doi.org/10.1172/JCI19246
Broeders, E. P., Nascimento, E. B., Havekes, B., Brans, B., Roumans, K. H., Tailleux, A., Schaart, G., Kouach, M., Charton, J., Deprez, B., Bouvy, N. D., Mottaghy, F., Staels, B., van Marken Lichtenbelt, W. D., & Schrauwen, P. (2015). The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metabolism, 22(3), 418–426. https://doi.org/10.1016/j.cmet.2015.07.002
Inagaki, T., Choi, M., Moschetta, A., Peng, L., Cummins, C. L., McDonald, J. G., Luo, G., Jones, S. A., Goodwin, B., Richardson, J. A., Gerard, R. D., Repa, J. J., Mangelsdorf, D. J., & Kliewer, S. A. (2005). Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metabolism, 2(4), 217–225. https://doi.org/10.1016/j.cmet.2005.09.001
Jones, B. V., Begley, M., Hill, C., Gahan, C. G., & Marchesi, J. R. (2008). Functional and comparative metagenomic analysis of bile salt hydrolase activity in the human gut microbiome. Proceedings of the National Academy of Sciences of the United States of America, 105(36), 13580–13585. https://doi.org/10.1073/pnas.0804437105
Makishima, M., Okamoto, A. Y., Repa, J. J., Tu, H., Learned, R. M., Luk, A., Hull, M. V., Lustig, K. D., Mangelsdorf, D. J., & Shan, B. (1999). Identification of a nuclear receptor for bile acids. Science, 284(5418), 1362–1365. https://doi.org/10.1126/science.284.5418.1362
Maruyama, T., Miyamoto, Y., Nakamura, T., Tamai, Y., Okada, H., Sugiyama, E., Nakamura, T., Itadani, H., & Tanaka, K. (2002). Identification of membrane-type receptor for bile acids. Biochemical and Biophysical Research Communications, 298(5), 714–719. https://doi.org/10.1016/s0006-291x(02)02550-0
Parséus, A., Sommer, N., Sommer, F., Caesar, R., Molinaro, A., Ståhlman, M., Greiner, T. U., Perkins, R., & Bäckhed, F. (2017). Microbiota-induced obesity requires farnesoid X receptor. Gut, 66(3), 429–437. https://doi.org/10.1136/gutjnl-2015-310283
Ridlon, J. M., Kang, D. J., & Hylemon, P. B. (2006). Bile salt biotransformations by human intestinal bacteria. Journal of Lipid Research, 47(2), 241–259. https://doi.org/10.1194/jlr.R500013-JLR200
Watanabe, M., Houten, S. M., Mataki, C., Christoffolete, M. A., Kim, B. W., Sato, H., Messaddeq, N., Harney, J. W., Ezaki, O., Kodama, T., Schoonjans, K., Bianco, A. C., & Auwerx, J. (2006). Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature, 439(7075), 484–489. https://doi.org/10.1038/nature04330
Abubucker, S., Segata, N., Goll, J., Schubert, A. M., Izard, J., Cantarel, B. L., Rodriguez-Mueller, B., Zucker, J., Thiagarajan, M., Henrissat, B., White, O., Kelley, S. T., Methé, B., Schloss, P. D., Gevers, D., Mitreva, M., & Huttenhower, C. (2012). Metabolic reconstruction for metagenomic data and its application to the human microbiome. PLOS Computational Biology, 8(6), e1002358. https://doi.org/10.1371/journal.pcbi.1002358
Callahan, B. J., McMurdie, P. J., Rosen, M. J., Han, A. W., Johnson, A. J., & Holmes, S. P. (2016). DADA2: High-resolution sample inference from Illumina amplicon data. Nature Methods, 13(7), 581–583. https://doi.org/10.1038/nmeth.3869
Caporaso, J. G., Lauber, C. L., Walters, W. A., Berg-Lyons, D., Lozupone, C. A., Turnbaugh, P. J., Fierer, N., & Knight, R. (2011). Global patterns of 16S rRNA diversity at a depth of millions of sequences per sample. Proceedings of the National Academy of Sciences of the United States of America, 108(Suppl. 1), 4516–4522. https://doi.org/10.1073/pnas.1000080107
Franzosa, E. A., McIver, L. J., Rahnavard, G., Thompson, L. R., Schirmer, M., Weingart, G., Lipson, K. S., Knight, R., Caporaso, J. G., Segata, N., & Huttenhower, C. (2018). Species-level functional profiling of metagenomes and metatranscriptomes. Nature Methods, 15(11), 962–968. https://doi.org/10.1038/s41592-018-0176-y
Gloor, G. B., Macklaim, J. M., Pawlowsky-Glahn, V., & Egozcue, J. J. (2017). Microbiome datasets are compositional: And this is not optional. Frontiers in Microbiology, 8, 2224. https://doi.org/10.3389/fmicb.2017.02224
Hasin, Y., Seldin, M., & Lusis, A. (2017). Multi-omics approaches to disease. Genome Biology, 18(1), 83. https://doi.org/10.1186/s13059-017-1215-1
Kaelberer, M. M., Buchanan, K. L., Klein, M. E., Barth, B. B., Montoya, M. M., Shen, X., & Bohórquez, D. V. (2018). A gut-brain neural circuit for nutrient sensory transduction. Science, 361(6408), eaat5236. https://doi.org/10.1126/science.aat5236
Kurtz, Z. D., Müller, C. L., Miraldi, E. R., Littman, D. R., Blaser, M. J., & Bonneau, R. A. (2015). Sparse and compositionally robust inference of microbial ecological networks. PLOS Computational Biology, 11(5), e1004226. https://doi.org/10.1371/journal.pcbi.1004226
Quince, C., Walker, A. W., Simpson, J. T., Loman, N. J., & Segata, N. (2017). Shotgun metagenomics, from sampling to analysis. Nature Biotechnology, 35(9), 833–844. https://doi.org/10.1038/nbt.3935
Topçuoğlu, B. D., Lesniak, N. A., Ruffin, M. T., 4th, Wiens, J., & Schloss, P. D. (2020). A framework for effective application of machine learning to microbiome-based classification problems. mBio, 11(3), e00434-20. https://doi.org/10.1128/mBio.00434-20
Berry, S. E., Valdes, A. M., Drew, D. A., Asnicar, F., Mazidi, M., Wolf, J., Capdevila, J., Hadjigeorgiou, G., Davies, R., Al Khatib, H., Bonnett, C., Ganesh, S., Bakker, E., Hart, D., Mangino, M., Merino, J., Linenberg, I., Wyatt, P., Ordovas, J. M., Gardner, C. D., … Spector, T. D. (2020). Human postprandial responses to food and potential for precision nutrition. Nature Medicine, 26(6), 964–973. https://doi.org/10.1038/s41591-020-0934-0
Borody, T. J., & Khoruts, A. (2011). Fecal microbiota transplantation and emerging applications. Nature Reviews Gastroenterology & Hepatology, 9(2), 88–96. https://doi.org/10.1038/nrgastro.2011.244
Goodrich, J. K., Waters, J. L., Poole, A. C., Sutter, J. L., Koren, O., Blekhman, R., Beaumont, M., Van Treuren, W., Knight, R., Bell, J. T., Spector, T. D., Clark, A. G., & Ley, R. E. (2014). Human genetics shape the gut microbiome. Cell, 159(4), 789–799. https://doi.org/10.1016/j.cell.2014.09.053
Salminen, S., Collado, M. C., Endo, A., Hill, C., Lebeer, S., Quigley, E. M. M., Sanders, M. E., Shamir, R., Swann, J. R., Szajewska, H., & Vinderola, G. (2021). The International Scientific Association of Probiotics and Prebiotics consensus statement on the definition and scope of postbiotics. Nature Reviews Gastroenterology & Hepatology, 18(9), 649–667. https://doi.org/10.1038/s41575-021-00440-6
Segata, N. (2015). Gut microbiome: Westernization and the disappearance of intestinal diversity. Current Biology, 25(14), R611–R613. https://doi.org/10.1016/j.cub.2015.05.040
Wang, Z., Roberts, A. B., Buffa, J. A., Levison, B. S., Zhu, W., Org, E., Gu, X., Huang, Y., Zamanian-Daryoush, M., Culley, M. K., DiDonato, A. J., Fu, X., Hazen, J. E., Krajcik, D., DiDonato, J. A., Lusis, A. J., & Hazen, S. L. (2015). Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell, 163(7), 1585–1595. https://doi.org/10.1016/j.cell.2015.11.055
Zhao, L., Zhang, F., Ding, X., Wu, G., Lam, Y. Y., Wang, X., Fu, H., Xue, X., Lu, C., Ma, J., Yu, L., Xu, C., Ren, Z., Xu, Y., Xu, S., Shen, H., Zhu, X., Shi, Y., Shen, Q., Dong, W., … Zhang, C. (2018). Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes. Science, 359(6380), 1151–1156. https://doi.org/10.1126/science.aao5774
Fogelson, K. A., Dorrestein, P. C., Zarrinpar, A., & Knight, R. (2023). The gut microbial bile acid modulation and its relevance to digestive health and diseases. Gastroenterology, 164(7), 1069–1085. https://doi.org/10.1053/j.gastro.2023.02.022
Downloads
Published
Issue
Section
License
Copyright (c) 2026 Karolina Wymoczył, Natalia Cieślak, Agata Chodkowska, Aleksandra Cyrkler, Kamila Czyżak, Urszula Marzec, Karol Dąbek, Eliza Rajca, Agnieszka Giza, Paulina Giza
This work is licensed under a Creative Commons Attribution 4.0 International License.
All articles are published in open-access and licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). Hence, authors retain copyright to the content of the articles.
CC BY 4.0 License allows content to be copied, adapted, displayed, distributed, re-published or otherwise re-used for any purpose including for adaptation and commercial use provided the content is attributed.
How to Cite
