Research Progress on the Regulation of the Gut Microbiota-Metabolism Axis by Probiotics for the Treatment of Inflammatory Bowel Disease

Main Article Content

Xinting Li
College of Horticulture, South China Agricultural University, Guangzhou 510642, China

DOI: https://doi.org/10.70267/emsgh.v3.105116

Keywords

inflammatory bowel disease, probiotics, gut microbiota-metabolic axis, short-chain fatty acids, bile acids, tryptophan

Abstract

Inflammatory bowel disease (IBD), which primarily includes ulcerative colitis (UC) and Crohn’s disease (CD), has seen a rapid rise in incidence in China in recent years. Traditional medications and biologics still face limitations such as limited targeting and a high risk of relapse upon discontinuation. Gut microbiota dysbiosis and the resulting metabolic disturbances are key pathological mechanisms underlying intestinal barrier damage and mucosal immune imbalance in IBD. This article focuses on the microbiota-metabolism axis to elucidate the physiological functions of three core metabolic pathways—short-chain fatty acids, bile acids, and tryptophan—and their pathological alterations in IBD. In addition, the regulatory mechanisms and clinical evidence of typical probiotics such as Clostridium butyricum, Escherichia coli, Faecalibacterium prausnitzii, Bifidobacterium and Limosilactobacillus reuteri on the above pathways were sorted out. Existing studies have shown that probiotics can play an anti-inflammatory role by refilling the exhausted metabolic pathways, repairing the intestinal epithelial barrier and regulating mucosal immunity, which is a safe and good auxiliary intervention for IBD. This article systematically reviews the above evidence to provide a reference for the subsequent mechanism research and clinical application of probiotics in IBD.

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References

  • [1]Guan, Q. (2019). A comprehensive review and update on the pathogenesis of inflammatory bowel disease. Journal of Immunology Research, 2019(1), Article 7247238. https://doi.org/10.1155/2019/7247238
  • [2]Shen, X., Li, Y., Wang, D., & Sun, K. (2025). The gut microbiota and its metabolites: Novel therapeutic targets for inflammatory bowel disease. Frontiers in Immunology, 16, Article 1690279. https://doi.org/10.3389/fimmu.2025.1690279
  • [3]Yang, X., Guo, H., & Zou, M. (2026). Inflammatory bowel diseases: Pathological mechanisms and therapeutic perspectives. Molecular Biomedicine, 7(1), Article 2. https://doi.org/10.1186/s43556-025-00395-z
  • [4]Hijová, E. (2025). Probiotics in IBD: Evidence and perspectives on patient health and disease management. International Journal of Molecular Sciences, 26(18), Article 9065. https://doi.org/10.3390/ijms26189065
  • [5]Giju, J. K., John, S., Sivadas, A., Prabhakar, M., K., K., Sunilkumar, D., Nair, B. G., Pal, S., & Prakash, V. (2026). From dysbiosis to precision medicine: Targeting the microbial–metabolic axis in IBD management. Frontiers in Cellular and Infection Microbiology, 16, Article 1826972. https://doi.org/10.3389/fcimb.2026.1826972
  • [6]Iliev, I. D., Ananthakrishnan, A. N., & Guo, C.-J. (2025). Microbiota in inflammatory bowel disease: Mechanisms of disease and therapeutic opportunities. Nature Reviews Microbiology, 23(8), 509–524. https://doi.org/10.1038/s41579-025-01163-0
  • [7]Ma, J., Wang, K., Wang, J., Zeng, Q., Liu, K., Zheng, S., Chen, Y., & Yao, J. (2024). Microbial disruptions in inflammatory bowel disease: A comparative analysis. International Journal of General Medicine, 17, 1355–1367. https://doi.org/10.2147/ijgm.s448359
  • [8]Dolan, K. T., & Chang, E. B. (2017). Diet, gut microbes, and the pathogenesis of inflammatory bowel diseases. Molecular Nutrition & Food Research, 61(1), Article 1600129. https://doi.org/10.1002/mnfr.201600129
  • [9]Liang, Y., Zhou, Y., Luo, P., & Lin, J. (2026). Gut microbiota metabolites in inflammatory bowel disease: Advances in mechanistic insights. Frontiers in Immunology, 17, Article 1827426. https://doi.org/10.3389/fimmu.2026.1827426
  • [10]Ventura, I., Chomon-García, M., Tomás-Aguirre, F., Palau-Ferré, A., Legidos-García, M. E., Murillo-Llorente, M. T., & Pérez-Bermejo, M. (2024). Therapeutic and immunologic effects of short-chain fatty acids in inflammatory bowel disease: A systematic review. International Journal of Molecular Sciences, 25(20), Article 10879. https://doi.org/10.3390/ijms252010879
  • [11]Sun, M., Wu, W., Liu, Z., & Cong, Y. (2017). Microbiota metabolite short chain fatty acids, GPCR, and inflammatory bowel diseases. Journal of Gastroenterology, 52(1), 1–8. https://doi.org/10.1007/s00535-016-1242-9
  • [12]Goldiș, A., Dragomir, R., Mercioni, M. A., Goldiș, C., Sirca, D., Enătescu, I., Olariu, L., & Belei, O. (2025). Personalized microbiome modulation to improve clinical outcomes in pediatric inflammatory bowel disease: A multi-omics and interventional approach. Microorganisms, 13(5), Article 1047. https://doi.org/10.3390/microorganisms13051047
  • [13]Karłowicz, K., Lewandowski, K., Tulewicz-Marti, E., & Rydzewska, G. (2026). A comprehensive review of usefulness of sodium butyrate for the management of inflammatory bowel disease: From molecular mechanisms to clinical application. Gastroenterology Review/Przegląd Gastroenterologiczny, 21(1), 29–37. https://doi.org/10.5114/pg.2026.159719
  • [14]Kou, R., Guo, Y., Qin, Z., Xu, X., Liu, Y., Wei, W., Chen, Y., Jian, Z., & Lan, B. (2025). Systemic dysregulation of the gut microenvironment plays a pivotal role in the onset and progression of inflammatory bowel disease. Frontiers in Immunology, 16, Article 1661386. https://doi.org/10.3389/fimmu.2025.1661386
  • [15]Fiorucci, S., Carino, A., Baldoni, M., Santucci, L., Costanzi, E., Graziosi, L., Distrutti, E., & Biagioli, M. (2021). Bile acid signaling in inflammatory bowel diseases. Digestive Diseases and Sciences, 66(3), 674–693. https://doi.org/10.1007/s10620-020-06715-3
  • [16]Di Vincenzo, F., Puca, P., Lopetuso, L. R., Petito, V., Masi, L., Bartocci, B., Murgiano, M., De Felice, M., Petronio, L., Gasbarrini, A., & Scaldaferri, F. (2022). Bile acid-related regulation of mucosal inflammation and intestinal motility: From pathogenesis to therapeutic application in IBD and microscopic colitis. Nutrients, 14(13), Article 2664. https://doi.org/10.3390/nu14132664
  • [17]Long, X.-Q., Liu, M.-Z., Liu, Z.-H., Xia, L.-Z., Lu, S.-P., Xu, X.-P., & Wu, M.-H. (2023). Bile acids and their receptors: Potential therapeutic targets in inflammatory bowel disease. World Journal of Gastroenterology, 29(27), 4252–4270. https://doi.org/10.3748/wjg.v29.i27.4252
  • [18]Jahnel, J., Fickert, P., Hauer, A. C., Högenauer, C., Avian, A., & Trauner, M. (2014). Inflammatory bowel disease alters intestinal bile acid transporter expression. Drug Metabolism and Disposition, 42(9), 1423–1431. https://doi.org/10.1124/dmd.114.058065
  • [19]Quinn, R. A., Melnik, A. V., Vrbanac, A., Fu, T., Patras, K. A., Christy, M. P., Bodai, Z., Belda-Ferre, P., Tripathi, A., Chung, L. K., Downes, M., Welch, R. D., Quinn, M., Humphrey, G., Panitchpakdi, M., Weldon, K. C., Aksenov, A., da Silva, R., Avila-Pacheco, J., . . . Dorrestein, P. C. (2020). Global chemical effects of the microbiome include new bile-acid conjugations. Nature, 579(7797), 123–129. https://doi.org/10.1038/s41586-020-2047-9
  • [20]Chen, L., Jiao, T., Liu, W., Luo, Y., Wang, J., Guo, X., Tong, X., Lin, Z., Sun, C., Wang, K., He, Y., Zhang, Y., Xu, H., Wang, J., Zuo, J., Ding, Q., He, S., Gonzalez, F. J., & Xie, C. (2022). Hepatic cytochrome P450 8B1 and cholic acid potentiate intestinal epithelial injury in colitis by suppressing intestinal stem cell renewal. Cell Stem Cell, 29(9), 1366–1381.e9. https://doi.org/10.1016/j.stem.2022.08.008
  • [21]Li, M.-L., Sun, S.-P., Sun, K., Lv, B., & Fan, Y.-H. (2023). Role of tryptophan metabolism in inflammatory bowel disease. World Chinese Journal of Digestology, 31(21), 896–903. https://doi.org/10.11569/wcjd.v31.i21.896
  • [22]Gao, H., Sun, M., Li, A., Gu, Q., Kang, D., Feng, Z., Li, X., Wang, X., Chen, L., Yang, H., Cong, Y., & Liu, Z. (2025). Microbiota-derived IPA alleviates intestinal mucosal inflammation through upregulating Th1/Th17 cell apoptosis in inflammatory bowel disease. Gut Microbes, 17(1), Article 2467235. https://doi.org/10.1080/19490976.2025.2467235
  • [23]Vich Vila, A., Zhang, J., Liu, M., Faber, K. N., & Weersma, R. K. (2024). Untargeted faecal metabolomics for the discovery of biomarkers and treatment targets for inflammatory bowel diseases. Gut, 73(11), 1909–1920. https://doi.org/10.1136/gutjnl-2023-329969
  • [24]Estevinho, M. M., Yuan, Y., Rodríguez‐Lago, I., Sousa‐Pimenta, M., Dias, C. C., Barreiro‐de Acosta, M., Jairath, V., & Magro, F. (2024). Efficacy and safety of probiotics in IBD: An overview of systematic reviews and updated meta-analysis of randomized controlled trials. United European Gastroenterology Journal, 12(7), 960–981. https://doi.org/10.1002/ueg2.12636
  • [25]Chulenbayeva, L., Jarmukhanov, Z., Kaliyekova, K., Kozhakhmetov, S., & Kushugulova, A. (2025). Quantitative alterations in short-chain fatty acids in inflammatory bowel disease: A systematic review and meta-analysis. Biomolecules, 15(7), Article 1017. https://doi.org/10.3390/biom15071017
  • [26]Grenda, T., Grenda, A., Domaradzki, P., Krawczyk, P., & Kwiatek, K. (2022). Probiotic potential of Clostridium spp.—Advantages and doubts. Current Issues in Molecular Biology, 44(7), 3118–3130. https://doi.org/10.3390/cimb44070215
  • [27]Qian, S., Li, S., Ye, K., Lu, S., Sha, X., Zhang, D., Xu, Z., Song, X., & Li, R. (2026). The role of Clostridium butyricum and its metabolites in modulating gut mucosal immunity: Implications for viral infections and inflammatory diseases. Frontiers in Immunology, 17, Article 1763817. https://doi.org/10.3389/fimmu.2026.1763817
  • [28]Lin, J. (2022). Efficacy of Clostridium butyricum capsule combined with infliximab on ulcerative colitis and its impacts on intestinal flora, serum IL-17, sICAM-1 and TNF-α levels. China Medicine and Pharmacy, 12(21), 197–200.
  • [29]Yasueda, A., Mizushima, T., Nezu, R., Sumi, R., Tanaka, M., Nishimura, J., Kai, Y., Hirota, M., Osawa, H., Nakajima, K., Mori, M., & Ito, T. (2016). The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis. Surgery Today, 46(8), 939–949. https://doi.org/10.1007/s00595-015-1261-9
  • [30]Scaldaferri, F., Gerardi, V., Mangiola, F., Lopetuso, L. R., Pizzoferrato, M., Petito, V., Papa, A., Stojanovic, J., Poscia, A., Cammarota, G., & Gasbarrini, A. (2016). Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: An update. World Journal of Gastroenterology, 22(24), 5505–5511. https://doi.org/10.3748/wjg.v22.i24.5505
  • [31]Ye, Z., Tan, Q., Woltemate, S., Tan, X., Römermann, D., Grassl, G. A., Vital, M., Seidler, U., & Kini, A. (2025). Escherichia coli Nissle improves short-chain fatty acid absorption and barrier function in a mouse model for chronic inflammatory diarrhea. Inflammatory Bowel Diseases, 31(4), 1109–1120. https://doi.org/10.1093/ibd/izae294
  • [32]Kruis, W., Frič, P., Pokrotnieks, J., Lukáš, M., Fixa, B., Kaščák, M., Kamm, M. A., Weismueller, J., Beglinger, C., Stolte, M., Wolff, C., & Schulze, J. (2004). Maintaining remission of ulcerative colitis with the probiotic Escherichia coli Nissle 1917 is as effective as with standard mesalazine. Gut, 53(11), 1617–1623. https://doi.org/10.1136/gut.2003.037747
  • [33]Matthes, H., Krummenerl, T., Giensch, M., Wolff, C., & Schulze, J. (2010). Clinical trial: Probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN). BMC Complementary and Alternative Medicine, 10(1), Article 13. https://doi.org/10.1186/1472-6882-10-13
  • [34]Mu, C., Zhao, Q., Zhao, Q., Yang, L., Pang, X., Liu, T., Li, X., Wang, B., Fung, S.-Y., & Cao, H. (2023). Multi-omics in Crohn's disease: New insights from inside. Computational and Structural Biotechnology Journal, 21, 3054–3072. https://doi.org/10.1016/j.csbj.2023.05.010
  • [35]Cao, Y., Shen, J., & Ran, Z. H. (2014). Association between Faecalibacterium prausnitzii reduction and inflammatory bowel disease: A meta-analysis and systematic review of the literature. Gastroenterology Research and Practice, 2014(1), Article 872725. https://doi.org/10.1155/2014/872725
  • [36]Sokol, H., Pigneur, B., Watterlot, L., Lakhdari, O., Bermúdez-Humarán, L. G., Gratadoux, J.-J., Blugeon, S., Bridonneau, C., Furet, J.-P., Corthier, G., Grangette, C., Vasquez, N., Pochart, P., Trugnan, G., Thomas, G., Blottière, H. M., Doré, J., Marteau, P., Seksik, P., & Langella, P. (2008). Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proceedings of the National Academy of Sciences, 105(43), 16731–16736. https://doi.org/10.1073/pnas.0804812105
  • [37]Lopez-Siles, M., Duncan, S. H., Garcia-Gil, L. J., & Martinez-Medina, M. (2017). Faecalibacterium prausnitzii: From microbiology to diagnostics and prognostics. The ISME Journal, 11(4), 841–852. https://doi.org/10.1038/ismej.2016.176
  • [38]Martín, R., Rios-Covian, D., Huillet, E., Auger, S., Khazaal, S., Bermúdez-Humarán, L. G., Sokol, H., Chatel, J.-M., & Langella, P. (2023). Faecalibacterium: A bacterial genus with promising human health applications. FEMS Microbiology Reviews, 47(4), Article fuad039. https://doi.org/10.1093/femsre/fuad039
  • [39]Gadaleta, R. M., Cariello, M., Crudele, L., & Moschetta, A. (2022). Bile salt hydrolase-competent probiotics in the management of IBD: Unlocking the “bile acid code.” Nutrients, 14(15), Article 3212. https://doi.org/10.3390/nu14153212
  • [40]Kriaa, A., Mariaule, V., Jablaoui, A., Rhimi, S., Mkaouar, H., Hernandez, J., Korkmaz, B., Lesner, A., Maguin, E., Aghdassi, A., & Rhimi, M. (2022). Bile acids: Key players in inflammatory bowel diseases? Cells, 11(5), Article 901. https://doi.org/10.3390/cells11050901
  • [41]Xiao, F., Dong, F., Li, X., Li, Y., Yu, G., Liu, Z., Wang, Y., & Zhang, T. (2022). Bifidobacterium longum CECT 7894 improves the efficacy of infliximab for DSS-induced colitis via regulating the gut microbiota and bile acid metabolism. Frontiers in Pharmacology, 13, Article 902337. https://doi.org/10.3389/fphar.2022.902337
  • [42]Sinha, S. R., Haileselassie, Y., Nguyen, L. P., Tropini, C., Wang, M., Becker, L. S., Sim, D., Jarr, K., Spear, E. T., Singh, G., Namkoong, H., Bittinger, K., Fischbach, M. A., Sonnenburg, J. L., & Habtezion, A. (2020). Dysbiosis-induced secondary bile acid deficiency promotes intestinal inflammation. Cell Host & Microbe, 27(4), 659–670.e5. https://doi.org/10.1016/j.chom.2020.01.021
  • [43]Astó, E., Méndez, I., Audivert, S., Farran-Codina, A., & Espadaler, J. (2019). The efficacy of probiotics, prebiotic inulin-type fructans, and synbiotics in human ulcerative colitis: A systematic review and meta-analysis. Nutrients, 11(2), Article 293. https://doi.org/10.3390/nu11020293
  • [44]Matsuoka, K., Uemura, Y., Kanai, T., Kunisaki, R., Suzuki, Y., Yokoyama, K., Yoshimura, N., & Hibi, T. (2018). Efficacy of Bifidobacterium breve fermented milk in maintaining remission of ulcerative colitis. Digestive Diseases and Sciences, 63(7), 1910–1919. https://doi.org/10.1007/s10620-018-4946-2
  • [45]Zhou, L., Song, W., Liu, T., Yan, T., He, Z., He, W., Lv, J., Zhang, S., Dai, X., Yuan, L., & Shi, L. (2024). Multi-omics insights into anti-colitis benefits of the synbiotic and postbiotic derived from wheat bran arabinoxylan and Limosilactobacillus reuteri. International Journal of Biological Macromolecules, 278, Article 134860. https://doi.org/10.1016/j.ijbiomac.2024.134860
  • [46]Hou, Q., Ye, L., Liu, H., Huang, L., Yang, Q., Turner, J. R., & Yu, Q. (2018). Lactobacillus accelerates ISCs regeneration to protect the integrity of intestinal mucosa through activation of STAT3 signaling pathway induced by LPLs secretion of IL-22. Cell Death & Differentiation, 25(9), 1657–1670. https://doi.org/10.1038/s41418-018-0070-2
  • [47]Ahl, D., Liu, H., Schreiber, O., Roos, S., Phillipson, M., & Holm, L. (2016). Lactobacillus reuteri increases mucus thickness and ameliorates dextran sulphate sodium-induced colitis in mice. Acta Physiologica, 217(4), 300–310. https://doi.org/10.1111/apha.12695
  • [48]Oliva, S., Di Nardo, G., Ferrari, F., Mallardo, S., Rossi, P., Patrizi, G., Cucchiara, S., & Stronati, L. (2012). Randomised clinical trial: The effectiveness of Lactobacillus reuteri ATCC 55730 rectal enema in children with active distal ulcerative colitis. Alimentary Pharmacology & Therapeutics, 35(3), 327–334. https://doi.org/10.1111/j.1365-2036.2011.04939.x
  • [49]Adamina, M., Gerasimidis, K., Sigall-Boneh, R., Zmora, O., de Buck van Overstraeten, A., Campmans-Kuijpers, M., Ellul, P., Katsanos, K., Kotze, P. G., Noor, N., Schäfli-Thurnherr, J., Vavricka, S., Wall, C., Wierdsma, N., Yassin, N., & Lomer, M. (2020). Perioperative dietary therapy in inflammatory bowel disease. Journal of Crohn's and Colitis, 14(4), 431–444. https://doi.org/10.1093/ecco-jcc/jjz160
  • [50]Preidis, G. A., Weizman, A. V., Kashyap, P. C., & Morgan, R. L. (2020). AGA technical review on the role of probiotics in the management of gastrointestinal disorders. Gastroenterology, 159(2), 708–738.e4. https://doi.org/10.1053/j.gastro.2020.05.060
  • [51]Han, T., Zhang, Y., Zheng, G., & Guo, Y. (2025). From pathogenic mechanisms to therapeutic perspectives: A review of gut microbiota and intestinal mucosal immunity in inflammatory bowel disease. Frontiers in Immunology, 16, Article 1704651. https://doi.org/10.3389/fimmu.2025.1704651

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Oct 30, 2026
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Research Progress on the Regulation of the Gut Microbiota-Metabolism Axis by Probiotics for the Treatment of Inflammatory Bowel Disease. (2026). Explore Medical Science and Global Health, 3, 105-116. https://doi.org/10.70267/emsgh.v3.105116