Allobaculum mucilyticum-Mediated Gut Barrier Dysfunction Exacerbates the Severity of Hypertriglyceridemic Acute...

Hypertriglyceridemic acute pancreatitis (HTGAP) is characterized by frequent severe complications and poor clinical prognosis. Recent evidence suggests that gut dysbiosis is correlated with pancreatic injury in HTGAP, although the precise mechanisms remain to be elucidated. Here, we found that experimental HTGAP mice exhibited gut dysbiosis and intestinal barrier dysfunction, accompanied by an abnormal increase in Allobaculum mucilyticum (A. mucilyticum) and a decrease in Akkermansia muciniphila (A. muciniphila). Administration of A. mucilyticum aggravated oxidative stress-associated intestinal barrier dysfunction, promoted bacterial translocation to the pancreas, and ultimately exacerbated pancreatic injury. Conversely, supplementation with A. muciniphila alleviated the severity of HTGAP by restoring mucus layer thickness and reducing intestinal pro-inflammatory macrophage polarization. These findings highlight the critical role of gut dysbiosis in HTGAP progression, mediated through the pro-inflammatory mucolytic pathobiont A. mucilyticum, and suggest that modulating gut microbiota may represent a novel therapeutic strategy for HTGAP.