PDLIM2 deficiency alters small intestinal epithelial metabolites, intestine length and faecal microbiota in mice
PDLIM2 is altered in chronic diseases associated with a westernised diet, including inflammatory bowel disease (IBD) and colon cancer, yet its role in the small intestine remains unexplored. This study investigates PDLIM2 in a murine dietary model, small intestinal organoids and epithelial fractions using transcriptomic, microbiomic, metabolomic and protein analyses. PDLIM2 is expressed in absorptive enterocytes throughout the human gastrointestinal tract but is uniquely enriched in a small intestinal stem cell population. PDLIM2-deficiency in mice altered intestinal anatomy, faecal microbiota composition, and ileal transcriptional levels of genes associated with immunological, metabolic and antimicrobial responses. Loss of PDLIM2 induced small intestinal expression of the adaptor protein WDFY1 and altered epithelial metabolite profiles, including phospholipid and oleic acid abundance, without sensitising animals to western diet-induced intestinal inflammation. These findings highlight a unique albeit modest role for PDLIM2 in small intestinal biology, linking immune, metabolic, and microbial networks under basal and diet-induced stress.