Vitamin D deficiency disrupts a host microbiota bile acid axis in aged mice to drive Faecalibaculum rodentium expansion and intestinal epithelial barrier dysfunction
This study investigates how vitamin D deficiency modulates the gut microbiome and intestinal epithelial barrier function during aging. Aged male C57BL6J mice, 18 months old, were subjected to a 16-week dietary intervention, receiving either a vitamin D3 deficient diet, called VDD, or a control diet containing 1000 IU per kg vitamin D3, called VDS. Compared to young cohorts, aged mice exhibited impaired intestinal barrier function, which was profoundly exacerbated by dietary vitamin D deficiency, as evidenced by increased gut permeability, elevated circulating lipopolysaccharide, and structural damage across the jejunum, ileum, and colon. Multi-omics integration revealed that vitamin D deficiency drove extensive spatial remodeling of the gut microbiota, notably the selective expansion of Faecalibaculum rodentium. This bacterium was confirmed as a major contributor to bile salt hydrolase activity, driving excessive bile acid deconjugation that precipitates epithelial junctional damage. These findings define a critical host, microbiota, and metabolite circuit governing intestinal homeostasis during aging and identify actionable metabolic targets for therapeutic intervention. Fecal and intestinal content samples were collected for 16S rRNA gene sequencing and metagenomic analysis.