Kefir and Its By-Products Supplementation Reduces Inflammation and Oxidative Stress, Improves Intestinal Barrier Integrity, and Modulates the Gut Microbiota in Animal Models of Inflammatory Bowel Disease: A Systematic Review.
UNLABELLED: Kefir is a beverage obtained by fermenting milk or sugary solutions with a symbiotic community of bacteria and yeasts, presenting promising antimicrobial, antioxidant, and immunomodulatory properties. This systematic review aimed to synthesize evidence from preclinical studies evaluating the effects of kefir or its by-products on biomarkers of inflammation, oxidative stress, and gut health in animal models of IBD. A systematic review was conducted in accordance with PRISMA guidelines, utilizing the PubMed/MEDLINE, Web of Science, Embase, and Scopus databases. The quality of the studies was assessed using SYRCLE’s Risk of Bias tool. Sixteen experimental studies were included, comprising 585 rodents with chemically induced colitis. The interventions included traditional milk kefir, rice and water kefir, as well as isolated microorganisms and kefir-derived supernatants. Most studies reported reductions in inflammatory cytokines (TNF-α, IL-1β, IL-6) and inflammatory enzymes (iNOS, COX-2, MPO), along with increases in anti-inflammatory cytokines (IL-10, IL-4). Reductions in MDA and H₂O₂ were reported, supporting the antioxidant effects of kefir and its derivatives. Changes in antioxidant enzyme activity, including SOD, were also observed. In addition, kefir modulated gut microbiota composition, upregulated the expression of tight junction proteins, and influenced immune and molecular signaling pathways. Improvements were also observed in clinical parameters of IBD models, including disease activity index, rectal bleeding, and histological damage. Kefir and its derivatives exhibit beneficial effects on inflammation, oxidative stress, gut permeability, and immune modulation in animal models of IBD, suggesting a potential alternative for treating these diseases in humans. Although the findings are promising, heterogeneity among study protocols and methodological limitations highlight the need for further studies. Registration PROSPERO number: CRD420251062931. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12602-026-10948-5.