Cross-tissue multiomics reveals that Akkermansia muciniphila counteracts metabolic syndrome by reprograming gut microbiota, oleoylethanolamide and the gut-hypothalamus axis

High fructose diet is a major risk factor for metabolic syndrome (MetS). The gut bacterium Akkermansia muciniphila (A. muciniphila) has been shown to improve fructose-induced MetS, but the underlying mechanism remains unclear. Here, we investigated how A. muciniphila modulates fructose-induced MetS using multitissue, multiomics studies encompassing gut microbiota, plasma and gut metabolome, and hypothalamus single cell RNA-sequencing. A. muciniphila colonization enriched beneficial gut bacteria, increased metabolites including bile acids, endocannabinoids, and vitamins, and activated genes related to oxytocin and vasopressin signaling in hypothalamic neurons. Multiomics network analysis prio