The membrane protein Amuc_1098 from Akkermansia muciniphila alleviates acute pancreatitis via TLR2 signaling and glycerophospholipid metabolism remodeling

作者：Lijuan Wang, Ruilin Zhang, Liangtao Zhao, Liuxiang Xiao, Xiaoyan Zhang, Lingyi Liu, Jiaju Wang, Kuiyuan Chen, Jinyang Li, Jinyang Li, Maosen Zhang, Jie Li, Jie Li, Wei Lin · 发表于：Nature Communications · 年份：2026 · DOI：10.1038/s41467-026-71140-5 · 被引用次数：2 · 研究领域：Pancreatitis Pathology and Treatment、Immune Response and Inflammation、Neonatal and Maternal Infections

Acute pancreatitis is a complex inflammatory disease with high morbidity and mortality, closely associated with intestinal barrier dysfunction, gut microbiota dysbiosis and abnormal lipid metabolism. Akkermansia muciniphila has been shown to exert beneficial effects on the host via bioactive components such as Amuc proteins. Here, we investigate the effect of Amuc_1098 on acute pancreatitis in mice induced by caerulein combined with lipopolysaccharide or L-arginine. We show that oral administration of Amuc_1098 reduces pancreatic tissue injury and the levels of serum amylase and lipase. Mechanistically, it suppressed NF-κB signaling partially dependent on TLR2, thereby reducing the levels of pro-inflammatory factors (TNF-α, IL-1β, IL-6) and the proportion of macrophages in the spleen, pancreas and intestine, and reversed downregulation of colonic tight junction proteins via TLR2 to protect intestinal barrier function. Amuc_1098 improves disrupted glycerophospholipid metabolism seen in both acute pancreatitis patients and mice. Together, these results suggest that Amuc_1098 alleviates acute pancreatitis severity by exerting anti-inflammatory effects, reducing macrophage infiltration, enhancing colonic tight junction proteins, and regulating intestinal flora and glycerophospholipid metabolism.