Vitamin D Deficiency Exacerbates d-Galactose-Induced Intestinal Barrier Dysfunction in a Murine Model of Intestinal Aging

Vitamin D deficiency is prevalent in the elderly population. The molecular mechanisms by which vitamin D influences the intestinal function in aging remain poorly understood. To address this, a 16 week dietary intervention using a vitamin D₃-withdraw diet (VDD) combined with d-galactose treatment was conducted in mice. We assessed the gut barrier integrity, immune response, and changes in microbiota composition. In the context of d-galactose-induced aging, VDD significantly reduced serum 25-hydroxyvitamin D₃ levels and exacerbated intestinal permeability and downregulation of ZO-1 and Occludin. VDD led to transcriptional suppression of antiviral defense and antigen presentation pathways in the colon, which correlated with decreased expression of the vitamin D receptor. Additionally, VDD caused detrimental shifts in the gut microbiota, characterized by a decline in beneficial genera including Lactobacillus and an increase in pathogenic genera including Allobaculum. These findings highlight the essential role of vitamin D in maintaining intestinal barrier function, antiviral immunity, and microbiota homeostasis during aging.