Modulation of dysregulated ATG5 and ATG16L1 expression in IBD by Akkermansia muciniphila and its extracellular vesicles (EVs)

Akkermansia muciniphila is a next-generation probiotic known for its ability to degrade mucin within the intestinal mucus layer. Notably, extracellular vesicles (EVs) derived from A. muciniphila can mimic many of the bacterium’s functional properties. Autophagy, a vital cellular mechanism, maintains homeostasis by recycling damaged cellular components. Key genes in this pathway, including ATG5 and ATG16L1 , are essential for autophagosome formation. In this study, we analyzed the expression levels of ATG5 and ATG16L1 in patients with ulcerative colitis (UC) and Crohn’s disease (CD) (two major forms of inflammatory bowel disease (IBD)) compared to healthy controls using real-time PCR. Additionally, we evaluated the regulatory effects of A. muciniphila and its EVs on these genes in an inflamed Caco-2 colonic epithelial cell model. Our findings revealed significant overexpression of both ATG5 and ATG16L1 in UC and CD patients relative to controls. In vitro, IL-1β-induced inflammation in Caco-2 cells led to marked dysregulation of autophagy-related genes, with ATG5 upregulated and ATG16L1 downregulated. Treatment with live A. muciniphila and its EVs modulated the expression of these genes in a dose-dependent manner. While live bacteria consistently reversed inflammation-induced gene dysregulation, EVs exhibited a biphasic response, with higher concentrations more effectively restoring ATG16L1 expression. These results suggest that A. muciniphila and its EVs may offer therapeutic potential for managing autophagy-related inflammatory disorders, particularly in the context of IBD.