The role of gut microbiota in modulating immune responses: a systematic review on implications for autoimmune diseases

Aditya B. Saran; Aditi B. Saran

doi:10.18203/2320-6012.ijrms20251651

Authors

Aditya B. Saran Hinduhridaysamrat Balasaheb Thackeray Medical College and Dr R. N. Cooper Municipal General Hospital, Mumbai, Maharashtra, India https://orcid.org/0009-0003-1933-6989
Aditi B. Saran Government Medical College, GT and Cama Hospital, Mumbai, Maharashtra, India

DOI:

https://doi.org/10.18203/2320-6012.ijrms20251651

Keywords:

Gut microbiota, Autoimmune diseases, Probiotics, Prebiotics, Fecal microbiota transplantation, Dysbiosis

Abstract

The gut microbiota plays a crucial role in immune regulation, influencing innate and adaptive immunity. Dysbiosis an imbalance in microbial composition has been linked to autoimmune diseases such as rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS), inflammatory bowel disease (IBD) and systemic lupus erythematosus (SLE). This review analyses sixteen studies, highlighting common dysbiosis patterns, including decreased short-chain fatty acid (SCFA)-producing bacteria (Faecalibacterium prausnitzii, Bifidobacterium) and increased pro-inflammatory bacteria (Prevotella copri, Akkermansia muciniphila). These shifts contribute to autoimmunity via molecular mimicry, increased gut permeability and immune dysregulation. Microbiota-targeted therapies such as probiotics, prebiotics, dietary interventions and fecal microbiota transplantation (FMT) show promise in restoring microbial balance and modulating immune responses. Probiotics (Lactobacillus reuteri) reduce inflammation in RA and MS, while FMT partially restores microbial diversity in IBD and MS. Despite progress, causality remains unclear, necessitating longitudinal studies and personalized microbiome-based interventions. Understanding the gut microbiota-autoimmunity relationship could pave the way for microbiome-driven immunotherapies.

Metrics

Metrics Loading ...

References

Romero Sender R, Fuchs S, Milo R. Are We Really Vastly Outnumbered? Revisiting the Ratio of Bacterial to Host Cells in Humans. Cell. 2016;164(3):337-40. DOI: https://doi.org/10.1016/j.cell.2016.01.013

Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. DOI: https://doi.org/10.1038/nature08821

Belkaid Y, Hand TW. Role of the microbiota in immunity and inflammation. Cell. 2014;157(1):121-41. DOI: https://doi.org/10.1016/j.cell.2014.03.011

Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. DOI: https://doi.org/10.1126/science.aan4236

Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):71-8. DOI: https://doi.org/10.1007/s12016-011-8291-x

Peters MD, Godfrey CM, McInerney P, Soares CB, Khalil H, Parker D. The Joanna Briggs institute reviewers’ manual 2015: Methodology for JBI scoping reviews. Adelaide: The Joanna Briggs Institute. 2015.

Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;:n71. DOI: https://doi.org/10.1136/bmj.n71

Zotero. Corporation for Digital Scholarship. Available at: https://zotero.org. Accessed on 10 February 2025.

Moher D, Liberati A, Tetzlaff J, Altman DG. for the PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. BMJ. 2009;339(1):2535–5. DOI: https://doi.org/10.1136/bmj.b2535

Round JL, Mazmanian SK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol. 2009;9(5):313-23. DOI: https://doi.org/10.1038/nri2515

Bevins CL, Salzman NH. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol. 2011;9(5):356-68. DOI: https://doi.org/10.1038/nrmicro2546

Koh A, De Vadder F, Kovatcheva-Datchary P, Bäckhed F. From Dietary Fiber to Host Physiology: Short-Chain Fatty Acids as Key Bacterial Metabolites. Cell. 2016;165(6):1332-45. DOI: https://doi.org/10.1016/j.cell.2016.05.041

Ivanov II, Atarashi K, Manel N, Brodie EL, Shima T, Karaoz U, et al. Induction of intestinal Th17 cells by segmented filamentous bacteria. Cell. 2009;139(3):485-98. DOI: https://doi.org/10.1016/j.cell.2009.09.033

Macpherson AJ, de Agüero MG, Ganal-Vonarburg SC. How nutrition and the maternal microbiota shape the neonatal immune system. Nat Rev Immunol. 2017;17(8):508-17. DOI: https://doi.org/10.1038/nri.2017.58

Scher JU, Sczesnak A, Longman RS, Segata N, Ubeda C, Bielski C, et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. Elife. 2013;2:1202. DOI: https://doi.org/10.7554/eLife.01202

Zhang X, Zhang D, Jia H, Feng Q, Wang D, Liang D, et al. The oral and gut microbiomes are perturbed in rheumatoid arthritis and partly normalized after treatment. Nat Med. 2015;21(8):895-905. DOI: https://doi.org/10.1038/nm.3914

VatanenT, Franzosa EA, Schwager R. The human gut microbiome in early-onset type 1 diabetes from the TEDDY study. Nature. 2018;562:589–94. DOI: https://doi.org/10.1038/s41586-018-0620-2

Knip M, Siljander H. The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol. 2016;12(3):154-67. DOI: https://doi.org/10.1038/nrendo.2015.218

Jangi S, Gandhi R, Cox LM, Li N, von Glehn F, Yan R, et al. Alterations of the human gut microbiome in multiple sclerosis. Nat Commun. 2016;28:12015. DOI: https://doi.org/10.1038/ncomms12015

Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, et al. The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis. Science. 2013;341(6145):569-73. DOI: https://doi.org/10.1126/science.1241165

Hughes RA, Cornblath DR. Guillain-Barré syndrome. Lancet. 2005;5;366(9497):1653-66. DOI: https://doi.org/10.1016/S0140-6736(05)67665-9

Marietta EV, Murray JA, Luckey DH, Jeraldo PR, Lamba A, Patel R, et al. Suppression of Inflammatory Arthritis by Human Gut-Derived Prevotella histicola in Humanized Mice. Arthritis Rheumatol. 2016;68(12):2878-88. DOI: https://doi.org/10.1002/art.39785

Makki K, Deehan EC, Walter J, Bäckhed F. The Impact of Dietary Fiber on Gut Microbiota in Host Health and Disease. Cell Host Microbe. 2018;13;23(6):705-15. DOI: https://doi.org/10.1016/j.chom.2018.05.012

Smits LP, Bouter KE, de Vos WM, Borody TJ, Nieuwdorp M. Therapeutic potential of fecal microbiota transplantation. Gastroenterology. 2013;145(5):946-53. DOI: https://doi.org/10.1053/j.gastro.2013.08.058

Jiang H, Ling Z, Zhang Y, Mao H, Ma Z, Yin Y, et al. Altered fecal microbiota composition in patients with major depressive disorder. Brain Behav Immun. 2015;48:186-94. DOI: https://doi.org/10.1016/j.bbi.2015.03.016

David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, et al. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014;505(7484):559-63. DOI: https://doi.org/10.1038/nature12820