TITLE: ““Cross-tissue multiomics studies reveal gutbrain interactions mediating the effect of Akkermansia muciniphila in counteracting fructose-induced obesity”
ABSTRACT: The gut bacterium Akkermansia muciniphila (A. muciniphila) has been implicated in anti-obesity effects, but a systems level understanding of the molecular mechanisms is lacking. We carried out multiomics studies to investigate the molecular cascades mediating the anti-obesity effect of A. muciniphila in a fructoseinduced obesity mouse model. We found that A. muciniphila colonization triggered significant shifts in gut microbiota composition, gut and plasma metabolites, and gene expression in hypothalamic neurons. Multiomics integration and network analysis prioritized the metabolite oleoylethanolamide (OEA) in the gut and circulation as a regulator of gut-brain interactions that underlie the A. muciniphila antiobesity effect. Oral administration of OEA counteracted the fructose-induced obesity through the regulation of hypothalamic anorexigenic neuropeptides such as oxytocin and arginine vasopressin. Our multiomics investigation and experimental validation elucidates the molecular regulators and pathways involved in the communication between A. muciniphila in the gut and hypothalamic neurons that counter fructose-induced obesity.
