The Gut–Immune Axis and Its Multisystem Repercussions: A Systematic Review of the Literature

Abstract

Introduction: The gut microbiota plays a central role in modulating the immune system by interacting with immune cells, epithelial barriers, and inflammatory mediators. Growing evidence indicates that microbial alterations impact multiple organ systems through the gut–immune axis. Aim: To systematically review the scientific literature to identify the multisystem repercussions of gut microbiota on the immune, rheumatologic, ophthalmologic, dermatologic, and gastrointestinal systems. Methodology: This is a systematic review conducted according to PRISMA guidelines. Searches were carried out in PubMed, Scopus, Embase, Web of Science, and SciELO between January 2015 and August 2025, using descriptors related to “gut microbiota,” “immune system,” and systemic diseases. Inclusion criteria comprised original human studies, peer-reviewed, available in English, Portuguese, or Spanish. Exclusion criteria included animal or in vitro studies, narrative reviews, editorials, and papers without full text. Results: The search identified 1,247 records, of which 16 were included in the qualitative synthesis. The gut microbiota influenced regulatory T cell and Th17 differentiation and cytokine production, including IL-6, IL-10, and TNF-α. In rheumatology, Prevotella copri was associated with rheumatoid arthritis. In dermatology, dysbiosis was linked to psoriasis, atopic dermatitis, and rosacea. In ophthalmology, autoimmune uveitis and ocular Sjögren’s syndrome were associated with microbial imbalance. In the gastrointestinal field, dysbiosis patterns were connected with inflammatory bowel diseases, irritable bowel syndrome, and metabolic disorders such as obesity and type 2 diabetes. Conclusion: The gut–immune axis plays an essential role in immune regulation with multisystemic impact. Modulation of gut microbiota emerges as a promising therapeutic strategy, although well-designed randomized trials are needed to establish diagnostic and therapeutic protocols.