Network topology of the gut microbiome associates with metabolic health in obesity

Abstract Obesity is a heterogeneous condition comprising a continuum of phenotypes with various metabolic and inflammatory profiles. Metabolically healthy obesity (MHO) identifies individuals with obesity but a relatively preserved metabolic state, although little is known about the gut microbiome features underlying this phenotype. Here, we analyzed gut microbial network structures of 931 individuals living with metabolically healthy non-obesity (MHNO), MHO, metabolically unhealthy non-obesity (MUNO), and metabolically unhealthy obesity (MUO), performing cross-sectional analyses on feces shotgun metagenomics data. Individuals with MHNO and MHO harbor more robust and functionally cohesive microbial networks, while communities from MUO and MUNO phenotypes exhibit a potentially dysbiotic state with reduced connectivity. A nutritional intervention cohort showed an improvement in network connectivity in parallel with metabolic improvements. Our findings show differences in microbial connectivity and association patterns across metabolic and obesity phenotypes, shedding light on how distinct microbial network structures may associate with host metabolic health and disease.