Role of the Gut Microbiome in the Pathogenesis of Crohn’s Disease
Abstract
Crohn's disease is one of the inflammatory bowel diseases (IBD) whose pathogenesis is still not fully understood. Many studies have shown a link between dysbiosis of the gut microbiome and the development of the disease. However, the specific mechanism linking the microbiota to inflammation in Crohn's disease is still open to further exploration. This study aims to investigate the role of the gut microbiome in the pathogenesis of Crohn's disease, specifically in differentiating the composition of the microbiota in patients with active disease and in remission. This study used a cross-sectional design with a sample of 100 patients diagnosed with Crohn's disease. Fecal samples were collected and analyzed using metagenomic techniques (16S rRNA sequencing) to identify the composition of the microbiota. Analysis of inflammatory biomarkers such as C-reactive protein (CRP) is also performed to assess disease status. The results showed that patients with active disease had a decrease in the number of anti-inflammatory bacteria such as Faecalibacterium prausnitzii and an increase in pathogenic bacteria such as Escherichia coli. In addition, there was a correlation between microbiome dysbiosis and increased CRP levels in patients with active disease. Microbiome dysbiosis has an important role in exacerbating the symptoms of Crohn's disease. This study provides evidence that the management of the gut microbiota can be a new therapeutic approach in the treatment of Crohn's disease.
Full text article
References
Alric, H., Amiot, A., Kirchgesner, J., Tréton, X., Allez, M., Bouhnik, Y., Beaugerie, L., Carbonnel, F., & Meyer, A. (2020). The effectiveness of either ustekinumab or vedolizumab in 239 patients with Crohn’s disease refractory to anti?tumour necrosis factor. Alimentary Pharmacology & Therapeutics, 51(10), 948–957. https://doi.org/10.1111/apt.15706
Bertani, L., Fornai, M., Fornili, M., Antonioli, L., Benvenuti, L., Tapete, G., Baiano Svizzero, G., Ceccarelli, L., Mumolo, M. G., Baglietto, L., De Bortoli, N., Bellini, M., Marchi, S., Costa, F., & Blandizzi, C. (2020). Serum oncostatin M at baseline predicts mucosal healing in Crohn’s disease patients treated with infliximab. Alimentary Pharmacology & Therapeutics, 52(2), 284–291. https://doi.org/10.1111/apt.15870
Biemans, V. B. C., Van Der Woude, C. J., Dijkstra, G., Van Der Meulen?de Jong, A. E., Löwenberg, M., De Boer, N. K., Oldenburg, B., Srivastava, N., Jansen, J. M., Bodelier, A. G. L., West, R. L., De Vries, A. C., Haans, J. J. L., De Jong, D., Hoentjen, F., Pierik, M. J., & the Dutch Initiative on Crohn and Colitis (ICC). (2020). Ustekinumab is associated with superior effectiveness outcomes compared to vedolizumab in Crohn’s disease patients with prior failure to anti?TNF treatment. Alimentary Pharmacology & Therapeutics, 52(1), 123–134. https://doi.org/10.1111/apt.15745
Bohm, M., Xu, R., Zhang, Y., Varma, S., Fischer, M., Kochhar, G., Boland, B., Singh, S., Hirten, R., Ungaro, R., Shmidt, E., Lasch, K., Jairaith, V., Hudesman, D., Chang, S., Lukin, D., Swaminath, A., Sands, B. E., Colombel, J., … the VICTORY Collaboration. (2020). Comparative safety and effectiveness of vedolizumab to tumour necrosis factor antagonist therapy for Crohn’s disease. Alimentary Pharmacology & Therapeutics, 52(4), 669–681. https://doi.org/10.1111/apt.15921
Chapuis?Biron, C., Bourrier, A., Nachury, M., Nancey, S., Bouhnik, Y., Serrero, M., Armengol?Debeir, L., Buisson, A., Tran?Minh, M., Zallot, C., Fumery, M., Bouguen, G., Abitbol, V., Viennot, S., Chanteloup, E., Rajca, S., Dib, N., Parmentier, A., Peyrin?Biroulet, L., … the GETAID BioLAP Study Group. (2020). Vedolizumab for perianal Crohn’s disease: A multicentre cohort study in 151 patients. Alimentary Pharmacology & Therapeutics, 51(7), 719–727. https://doi.org/10.1111/apt.15665
Chapuis-Biron, C., Kirchgesner, J., Pariente, B., Bouhnik, Y., Amiot, A., Viennot, S., Serrero, M., Fumery, M., Allez, M., Siproudhis, L., Buisson, A., Pineton De Chambrun, G., Abitbol, V., Nancey, S., Caillo, L., Plastaras, L., Savoye, G., Chanteloup, E., Simon, M., … the GETAID BioLAP Study Group. (2020). Ustekinumab for Perianal Crohn’s Disease: The BioLAP Multicenter Study From the GETAID. American Journal of Gastroenterology, 115(11), 1812–1820. https://doi.org/10.14309/ajg.0000000000000810
Dharmasiri, S., Garrido-Martin, E. M., Harris, R. J., Bateman, A. C., Collins, J. E., Cummings, J. R. F., & Sanchez-Elsner, T. (2021). Human Intestinal Macrophages Are Involved in the Pathology of Both Ulcerative Colitis and Crohn Disease. Inflammatory Bowel Diseases, 27(10), 1641–1652. https://doi.org/10.1093/ibd/izab029
Garcia-Olmo, D., Gilaberte, I., Binek, M., D´Hoore, A. J. L., Lindner, D., Selvaggi, F., Spinelli, A., & Panés, J. (2022). Follow-up Study to Evaluate the Long-term Safety and Efficacy of Darvadstrocel (Mesenchymal Stem Cell Treatment) in Patients With Perianal Fistulizing Crohn’s Disease: ADMIRE-CD Phase 3 Randomized Controlled Trial. Diseases of the Colon & Rectum, 65(5), 713–720. https://doi.org/10.1097/DCR.0000000000002325
Goodsall, T. M., Jairath, V., Feagan, B. G., Parker, C. E., Nguyen, T. M., Guizzetti, L., Asthana, A. K., Begun, J., Christensen, B., Friedman, A. B., Kucharzik, T., Lee, A., Lewindon, P. J., Maaser, C., Novak, K. L., Rimola, J., Taylor, K. M., Taylor, S. A., White, L. S., … Ma, C. (2021). Standardisation of intestinal ultrasound scoring in clinical trials for luminal Crohn’s disease. Alimentary Pharmacology & Therapeutics, 53(8), 873–886. https://doi.org/10.1111/apt.16288
Gordon, I. O., Bettenworth, D., Bokemeyer, A., Srivastava, A., Rosty, C., De Hertogh, G., Robert, M. E., Valasek, M. A., Mao, R., Li, J., Harpaz, N., Borralho, P., Pai, R. K., Odze, R., Feakins, R., Parker, C. E., Guizzetti, L., Nguyen, T., Shackelton, L. M., … Rieder, F. (2022). International consensus to standardise histopathological scoring for small bowel strictures in Crohn’s disease. Gut, 71(3), 479–486. https://doi.org/10.1136/gutjnl-2021-324374
Hammoudi, N., Auzolle, C., Tran Minh, M.-L., Boschetti, G., Bezault, M., Buisson, A., Pariente, B., Treton, X., Seksik, P., Fumery, M., Le Bourhis, L., Nancey, S., Allez, M., & on behalf of the REMIND group. (2020). Postoperative Endoscopic Recurrence on the Neoterminal Ileum But Not on the Anastomosis Is Mainly Driving Long-Term Outcomes in Crohn’s Disease. American Journal of Gastroenterology, 115(7), 1084–1093. https://doi.org/10.14309/ajg.0000000000000638
Iborra, M., Beltrán, B., Fernández?Clotet, A., Iglesias?Flores, E., Navarro, P., Rivero, M., Gutiérrez, A., Sierra?Ausin, M., Mesonero, F., Ferreiro?Iglesias, R., Hinojosa, J., Calvet, X., Sicilia, B., González?Muñoza, C., Antolín, B., González?Vivo, M., Carbajo, A. Y., García?López, S., Martín?Cardona, A., … GETECCU group (Grupo Español de trabajo de Enfermedades de Crohn y Colitis Ulcerosa). (2020). Real?world long?term effectiveness of ustekinumab in Crohn’s disease: Results from the ENEIDA registry. Alimentary Pharmacology & Therapeutics, 52(6), 1017–1030. https://doi.org/10.1111/apt.15958
Jongsma, M. M. E., Aardoom, M. A., Cozijnsen, M. A., Van Pieterson, M., De Meij, T., Groeneweg, M., Norbruis, O. F., Wolters, V. M., Van Wering, H. M., Hojsak, I., Kolho, K.-L., Hummel, T., Stapelbroek, J., Van Der Feen, C., Van Rheenen, P. F., Van Wijk, M. P., Teklenburg-Roord, S. T. A., Schreurs, M. W. J., Rizopoulos, D., … De Ridder, L. (2022). First-line treatment with infliximab versus conventional treatment in children with newly diagnosed moderate-to-severe Crohn’s disease: An open-label multicentre randomised controlled trial. Gut, 71(1), 34–42. https://doi.org/10.1136/gutjnl-2020-322339
Kalman, T. D., Everhov, Å. H., Nordenvall, C., Sachs, M. C., Halfvarson, J., Ekbom, A., Ludvigsson, J. F., Myrelid, P., & Olén, O. (2020). Decrease in primary but not in secondary abdominal surgery for Crohn’s disease: Nationwide cohort study, 1990–2014. British Journal of Surgery, 107(11), 1529–1538. https://doi.org/10.1002/bjs.11659
Ko, Y., Paramsothy, S., Yau, Y., & Leong, R. W. (2021). Superior treatment persistence with ustekinumab in Crohn’s disease and vedolizumab in ulcerative colitis compared with anti?TNF biological agents: Real?world registry data from the Persistence Australian National IBD Cohort (PANIC) study. Alimentary Pharmacology & Therapeutics, 54(3), 292–301. https://doi.org/10.1111/apt.16436
Kopylov, U., Hanzel, J., Liefferinckx, C., De Marco, D., Imperatore, N., Plevris, N., Baston?Rey, I., Harris, R. J., Truyens, M., Domislovic, V., Vavricka, S., Biemans, V., Myers, S., Sebastian, S., Ben?Horin, S., González Lama, Y., Gilletta, C., Ariella, B. S., Zelinkova, Z., … Drobne, D. (2020). Effectiveness of ustekinumab dose escalation in Crohn’s disease patients with insufficient response to standard?dose subcutaneous maintenance therapy. Alimentary Pharmacology & Therapeutics, 52(1), 135–142. https://doi.org/10.1111/apt.15784
Lafeuille, P., Hordonneau, C., Vignette, J., Blayac, L., Dapoigny, M., Reymond, M., Rouquette, O., Sollelis, E., Boube, M., Magnin, B., Pereira, B., & Buisson, A. (2021). Transmural healing and MRI healing are associated with lower risk of bowel damage progression than endoscopic mucosal healing in Crohn’s disease. Alimentary Pharmacology & Therapeutics, 53(5), 577–586. https://doi.org/10.1111/apt.16232
Leccese, G., Bibi, A., Mazza, S., Facciotti, F., Caprioli, F., Landini, P., & Paroni, M. (2020). Probiotic Lactobacillus and Bifidobacterium Strains Counteract Adherent-Invasive Escherichia coli (AIEC) Virulence and Hamper IL-23/Th17 Axis in Ulcerative Colitis, but Not in Crohn’s Disease. Cells, 9(8), 1824. https://doi.org/10.3390/cells9081824
Lightner, A. L., Vogel, J. D., Carmichael, J. C., Keller, D. S., Shah, S. A., Mahadevan, U., Kane, S. V., Paquette, I. M., Steele, S. R., & Feingold, • Daniel L. (2020). The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Surgical Management of Crohn’s Disease. Diseases of the Colon & Rectum, 63(8), 1028–1052. https://doi.org/10.1097/DCR.0000000000001716
Liu, B., Ye, D., Yang, H., Song, J., Sun, X., Mao, Y., & He, Z. (2022). Two-Sample Mendelian Randomization Analysis Investigates Causal Associations Between Gut Microbial Genera and Inflammatory Bowel Disease, and Specificity Causal Associations in Ulcerative Colitis or Crohn’s Disease. Frontiers in Immunology, 13, 921546. https://doi.org/10.3389/fimmu.2022.921546
Logan, M., Gkikas, K., Svolos, V., Nichols, B., Milling, S., Gaya, D. R., Seenan, J. P., Macdonald, J., Hansen, R., Ijaz, U. Z., Russell, R. K., & Gerasimidis, K. (2020). Analysis of 61 exclusive enteral nutrition formulas used in the management of active Crohn’s disease—New insights into dietary disease triggers. Alimentary Pharmacology & Therapeutics, 51(10), 935–947. https://doi.org/10.1111/apt.15695
Luglio, G., Rispo, A., Imperatore, N., Giglio, M. C., Amendola, A., Tropeano, F. P., Peltrini, R., Castiglione, F., De Palma, G. D., & Bucci, L. (2020). Surgical Prevention of Anastomotic Recurrence by Excluding Mesentery in Crohn’s Disease: The SuPREMe-CD Study - A Randomized Clinical Trial. Annals of Surgery, 272(2), 210–217. https://doi.org/10.1097/SLA.0000000000003821
Manlay, L., Boschetti, G., Pereira, B., Flourié, B., Dapoigny, M., Reymond, M., Sollelis, E., Gay, C., Boube, M., Buisson, A., & Nancey, S. (2021). Comparison of short? and long?term effectiveness between ustekinumab and vedolizumab in patients with Crohn’s disease refractory to anti?tumour necrosis factor therapy. Alimentary Pharmacology & Therapeutics, 53(12), 1289–1299. https://doi.org/10.1111/apt.16377
Mao, R., Doyon, G., Gordon, I. O., Li, J., Lin, S., Wang, J., Le, T. H. N., Elias, M., Kurada, S., Southern, B., Olman, M., Chen, M., Zhao, S., Dejanovic, D., Chandra, J., Mukherjee, P. K., West, G., Van Wagoner, D. R., Fiocchi, C., & Rieder, F. (2022). Activated intestinal muscle cells promote preadipocyte migration: A novel mechanism for creeping fat formation in Crohn’s disease. Gut, 71(1), 55–67. https://doi.org/10.1136/gutjnl-2020-323719
Nagayama, M., Yano, T., Atarashi, K., Tanoue, T., Sekiya, M., Kobayashi, Y., Sakamoto, H., Miura, K., Sunada, K., Kawaguchi, T., Morita, S., Sugita, K., Narushima, S., Barnich, N., Isayama, J., Kiridooshi, Y., Shiota, A., Suda, W., Hattori, M., … Honda, K. (2020). TH1 cell-inducing Escherichia coli strain identified from the small intestinal mucosa of patients with Crohn’s disease. Gut Microbes, 12(1), 1788898. https://doi.org/10.1080/19490976.2020.1788898
Olaisen, M., Flatberg, A., Granlund, A. V. B., Røyset, E. S., Martinsen, T. C., Sandvik, A. K., & Fossmark, R. (2021). Bacterial Mucosa-associated Microbiome in Inflamed and Proximal Noninflamed Ileum of Patients With Crohn’s Disease. Inflammatory Bowel Diseases, 27(1), 12–24. https://doi.org/10.1093/ibd/izaa107
Papamichael, K., Vande Casteele, N., Jeyarajah, J., Jairath, V., Osterman, M. T., & Cheifetz, A. S. (2021). Higher Postinduction Infliximab Concentrations Are Associated With Improved Clinical Outcomes in Fistulizing Crohn’s Disease: An ACCENT-II Post Hoc Analysis. American Journal of Gastroenterology, 116(5), 1007–1014. https://doi.org/10.14309/ajg.0000000000001111
Park, K. T., Ehrlich, O. G., Allen, J. I., Meadows, P., Szigethy, E. M., Henrichsen, K., Kim, S. C., Lawton, R. C., Murphy, S. M., Regueiro, M., Rubin, D. T., Engel-Nitz, N. M., & Heller, C. A. (2020a). The Cost of Inflammatory Bowel Disease: An Initiative From the Crohn’s & Colitis Foundation. Inflammatory Bowel Diseases, 26(1), 1–10. https://doi.org/10.1093/ibd/izz104
Park, K. T., Ehrlich, O. G., Allen, J. I., Meadows, P., Szigethy, E. M., Henrichsen, K., Kim, S. C., Lawton, R. C., Murphy, S. M., Regueiro, M., Rubin, D. T., Engel-Nitz, N. M., & Heller, C. A. (2020b). The Cost of Inflammatory Bowel Disease: An Initiative From the Crohn’s & Colitis Foundation. Inflammatory Bowel Diseases, 26(1), 1–10. https://doi.org/10.1093/ibd/izz104
Plevris, N., Jenkinson, P. W., Arnott, I. D., Jones, G. R., & Lees, C. W. (2020). Higher anti-tumor necrosis factor levels are associated with perianal fistula healing and fistula closure in Crohn’s disease. European Journal of Gastroenterology & Hepatology, 32(1), 32–37. https://doi.org/10.1097/MEG.0000000000001561
Sands, B. E., Feagan, B. G., Sandborn, W. J., Schreiber, S., Peyrin-Biroulet, L., Frédéric Colombel, J., Rossiter, G., Usiskin, K., Ather, S., Zhan, X., & D’Haens, G. (2020). Mongersen (GED-0301) for Active Crohn’s Disease: Results of a Phase 3 Study. American Journal of Gastroenterology, 115(5), 738–745. https://doi.org/10.14309/ajg.0000000000000493
Siegel, C. A., Yang, F., Eslava, S., & Cai, Z. (2020). Treatment Pathways Leading to Biologic Therapies for Ulcerative Colitis and Crohn’s Disease in the United States. Clinical and Translational Gastroenterology, 11(2), e00128. https://doi.org/10.14309/ctg.0000000000000128
Stidham, R. W., Enchakalody, B., Waljee, A. K., Higgins, P. D. R., Wang, S. C., Su, G. L., Wasnik, A. P., & Al-Hawary, M. (2020). Assessing Small Bowel Stricturing and Morphology in Crohn’s Disease Using Semi-automated Image Analysis. Inflammatory Bowel Diseases, 26(5), 734–742. https://doi.org/10.1093/ibd/izz196
Stournaras, E., Qian, W., Pappas, A., Hong, Y. Y., Shawky, R., UK IBD BioResource Investigators, Raine, T., & Parkes, M. (2021). Thiopurine monotherapy is effective in ulcerative colitis but significantly less so in Crohn’s disease: Long-term outcomes for 11 928 patients in the UK inflammatory bowel disease bioresource. Gut, 70(4), 677–686. https://doi.org/10.1136/gutjnl-2019-320185
Townsend, T., Razanskaite, V., Dodd, S., Storey, D., Michail, S., Morgan, J., Davies, M., Penman, D., Watters, C., Swaminathan, M., Sabine, J., Chapman, A., Smith, P. J., Flanagan, P. K., Reilly, I., Bodger, K., & Subramanian, S. (2020). Comparative effectiveness of ustekinumab or vedolizumab after one year in 130 patients with anti?TNF?refractory Crohn’s disease. Alimentary Pharmacology & Therapeutics, 52(8), 1341–1352. https://doi.org/10.1111/apt.16057
Wang, Y., Gao, X., Zhang, X., Xiao, F., Hu, H., Li, X., Dong, F., Sun, M., Xiao, Y., Ge, T., Li, D., Yu, G., Liu, Z., & Zhang, T. (2021). Microbial and metabolic features associated with outcome of infliximab therapy in pediatric Crohn’s disease. Gut Microbes, 13(1), 1865708. https://doi.org/10.1080/19490976.2020.1865708
Xiong, Y., Mizuno, T., Colman, R., Hyams, J., Noe, J. D., Boyle, B., Tsai, Y., Dong, M., Jackson, K., Punt, N., Rosen, M. J., Denson, L. A., Vinks, A. A., & Minar, P. (2021). Real?World Infliximab Pharmacokinetic Study Informs an Electronic Health Record?Embedded Dashboard to Guide Precision Dosing in Children with Crohn’s Disease. Clinical Pharmacology & Therapeutics, 109(6), 1639–1647. https://doi.org/10.1002/cpt.2148
Yang, C., Yu, H., Hu, X., Chen, H., Wu, H., Deng, C., & Sun, N. (2021). Gold?Doped Covalent Organic Framework Reveals Specific Serum Metabolic Fingerprints as Point of Crohn’s Disease Diagnosis. Advanced Functional Materials, 31(45), 2105478. https://doi.org/10.1002/adfm.202105478
Yang, E., Panaccione, N., Whitmire, N., Dulai, P. S., Vande Casteele, N., Singh, S., Boland, B. S., Collins, A., Sandborn, W. J., Panaccione, R., & Battat, R. (2020). Efficacy and safety of simultaneous treatment with two biologic medications in refractory Crohn’s disease. Alimentary Pharmacology & Therapeutics, 51(11), 1031–1038. https://doi.org/10.1111/apt.15719
Zhao, J., Han, H., Zhong, B., Xie, W., Chen, Y., & Zhi, M. (2021). Health information on social media helps mitigate Crohn’s disease symptoms and improves patients’ clinical course. Computers in Human Behavior, 115, 106588. https://doi.org/10.1016/j.chb.2020.106588
Authors
Copyright (c) 2025 Ahmet Demir, Sevda Kara, Javlonbek Khamraev

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.