Diversity of oligosaccharides in lipooligosaccharides of Akkermansia muciniphila and its anti-atherosclerotic activity

Abstract As an important and beneficial gut commensal, Akkermansia muciniphila plays a crucial role in regulating host metabolism and immunity. Lipooligosaccharides from A. muciniphila (ALOS) show anti-obesity effects in high-fat diet-fed mice. Herein, we investigated the chemical characteristics of core oligosaccharides of ALOS and explored its anti-atherosclerotic efficacy. The LC-Q-TOF-MS analysis indicated a high structural diversity of core oligosaccharides in ALOS, comprising fourteen distinct oligosaccharide species with different degrees of phosphorylation. Functionally, administration of ALOS significantly attenuated hyperlipidemia and reduced atherosclerotic plaque burden in high-fat diet-fed ApoE −/− mice. The improvement of these metabolic symptoms was related to the restoration of intestinal barrier integrity. Mechanistically, ALOS upregulated the IL-23/IL-22 immune axis, which in turn promoted intestinal epithelial repair and modulates the microbiota. ALOS intervention reshaped the gut microbiota composition by enriching beneficial genera such as Bifidobacterium longum , Roseburia intestinalis , and Oscillibacter sp. , while suppressing potential pathobionts. Our findings highlight the structural diversity and anti-atherosclerotic effect of lipooligosaccharides from A. muciniphila . Graphical Abstract