摘要Akkermansia,a next-generation probiotic candidate,exhibits a reduced abundance in obesity yet persists in the gut,suggesting unique adaptive mechanisms for survival in this adverse metabolic environment.To elucidate these mechanisms,a comparative pan-genome analysis of 494 Akkermansia metagenome-assembled genomes from hosts with diverse body mass indices was conducted.It was found that the genus possesses high genetic diversity,with Akkermansia muciniphila as the dominant species(80%),though species distribution itself was not correlated with BMI.There were 15 genes significantly enriched in obese individuals.These genes may potentially be involved in pathways such as nutrient acquisition,antioxidant stress response,energy metabolism,translational fidelity,and viral defense.Co-occurrence network analysis showed that these genes are associated with pathways including the tricarboxylic acid cycle and lipoic acid metabolism.These findings suggest potential adaptive functional mechanisms of Akkermansia for survival in the obese gut environment,providing novel insights for the development of targeted probiotics addressing obesity-related conditions.