Lard promotes intestinal stem/progenitor cell proliferation and differentiation with improved gut microbiota

The effects of dietary fats on the intestinal barrier have been widely studied, yet their role in intestinal repair remains unclear. Previous studies have primarily focused on fat quantity (e.g., high-fat vs. low-fat diets) and quality (e.g., saturated vs. unsaturated fats), while neglecting the importance of structural properties. This study evaluated the impact of dietary fats with varying <em>sn</em>-2 palmitate levels on intestinal repair using a DSS-induced murine injury model under moderate intake levels. The results indicated that lard, rich in <em>sn</em>-2 palmitate, significantly lowered intestinal permeability, reduced crypt damage, and decreased apoptosis in mice compared to fats low in <em>sn</em>-2 palmitate (corn oil and beef tallow). Immunohistochemical analysis demonstrated that lard significantly increased the number of SOX9, Ki67, MUC2, and PAS-positive cells per crypt, indicating enhanced proliferation and differentiation of intestinal stem/progenitor cells, thereby facilitating intestinal repair. Untargeted metabolomics analysis revealed distinct metabolic profiles of intestinal digestive products derived from dietary fats, with lard leading to enrichment of metabolites such as diacylglycerols, palmitoylcarnitine, and adhumulinic acid. The microbial results showed that lard improved α-diversity and increased the abundance of beneficial bacteria such as <em>unclassified_Lachnospiraceae, unclassified_Muribaculaceae</em>, and <em>Ligilactobacillus</em>. KEGG pathway analysis further demonstrated that lard enriched microbial pathways associated with replication and repair, translation, and amino acid metabolism. Our findings reveal that moderate intake of lard promotes intestinal repair, which is associated with beneficial shifts in metabolite profiles and gut microbiota composition. These results highlight the significance of the <em>sn</em>-2 palmitate structure in dietary fat interventions for promoting intestinal repair.