Long-term moderate lard intake reduces susceptibility to colitis and secondary liver injury in mice.

The role of dietary fats in inflammatory bowel disease is source-dependent. Lard has long been considered a less favorable dietary fat, yet its effects on intestinal health may be dose-dependent, and the mechanisms remain poorly understood. In this study, a dextran sulfate sodium (DSS)-induced colitis model was used to investigate the effects of moderate intake of different dietary fats-lard, beef tallow (beef), and corn oil (corn)-on colitis and secondary liver injury. We found that, compared to beef or corn, lard reduced susceptibility to DSS-induced colitis, as evidenced by less severe colonic inflammation, enhanced intestinal barrier integrity with upregulation of tight junction proteins (ZO-1, Occludin, Claudin1), and reduced colonic and systemic levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6). Moreover, lard-fed mice exhibited less severe secondary liver injury than beef- or corn-fed mice, as indicated by decreased serum ALT/AST levels, lower hepatic LPS accumulation, and reduced oxidative stress markers (MDA, protein carbonyl, 3-nitrotyrosine). Untargeted metabolomics revealed that lard enriched specific intestinal metabolites, including crispolide, steviol, swertiamarin, genipin, and several diglycerides. Hepatic transcriptomics and RT-qPCR validation further showed that lard specifically activated the PPAR signaling pathway and fatty acid degradation pathway, which was corroborated at the protein level by elevated PPARα and PPARγ expression. Spearman correlation analysis established positive associations between key intestinal metabolites and critical genes involved in these pathways. These results demonstrated that moderate lard intake reduced susceptibility to DSS-induced colitis and secondary liver injury compared to beef or corn, potentially through modulation of gut-liver crosstalk.