Therapeutic Effects of Camel Milk Exosomes and Their miR-148a-3p Cargo on DSS-Induced Colitis: Modulating Gut Inflammation through the SIRT1/NF-κB Pathway and Microbiota Alterations

Camel milk contains abundant bioactive compounds, but the therapeutic potential of its exosomes as natural delivery systems for gut health remains unclear. This study investigated the therapeutic effects and underlying mechanisms of camel milk exosomes (CME) and their enriched miRNA cargo, miR-148a-3p, on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice. Both CME and miR-148a-3p significantly alleviated colitis symptoms, including weight loss, colon shortening, and disease activity scores. These effects were achieved by suppressing pro-inflammatory cytokines and restoring intestinal barrier integrity through Zonula Occludens-1 (ZO-1) upregulation. Moreover, the treatments promoted M2 macrophage polarization, inhibited NF-κB signaling via silent information regulator T1 (SIRT1) upregulation and increased microbial diversity with the enrichment of beneficial taxa. Notably, the therapeutic effects of miR-148a-3p were comparable to those of CME, underscoring its role as a key functional component. These findings highlight CME as promising natural nanotherapeutics for UC, offering a novel, multitargeted strategy for managing intestinal inflammation.