Preventive effects of sheep milk on DSS-induced colitis in mice: modulation of gut microbiota and inflammatory responses

Abstract

This study explores the potential of sheep milk (SM) as a therapeutic treatment for ulcerative colitis (UC) in mice, focusing on its dose-dependent effects. Sheep milk, known for its rich bioactive compounds, shows significant anti-inflammatory and antioxidant properties. Using a combination of ELISA, qPCR, IHC, microbiome analysis, and untargeted metabolomics, we examined how SM protects against UC. The results revealed that SM treatment reduced the expression of pro-inflammatory cytokines (IL-1β, TNF-α), inflammatory markers (COX-2, iNOS), and TLR-4 in mice with DSS-induced colitis. Additionally, SM increased the levels of MUC2, MUC3, and key tight junction proteins (ZO-1, claudin-1, occludin), helping to restore the intestinal barrier. Microbiome analysis and metabolomics showed that SM helped balance the gut microbiota and boosted beneficial short-chain fatty acids. These findings suggest that sheep milk supplementation significantly modulated beneficial gut microbiota groups, including Akkermansia and Lactobacillus, showing promise as a dietary intervention for improving gut health and managing inflammatory bowel disease.