Microbiome and Metabolomics in Obesity: Advances in Understanding and Interventions Across the Lifespan
ABSTRACT Obesity arises from intertwined and reciprocal diet‐microbiome‐host pathways that reshape energy balance, insulin sensitivity, and inflammation. This review synthesizes mechanistic links between microbial functions and metabolic control, charts lifestyle‐related lifecourse dynamics from birth to older age, examines how GLP‐1‐based therapies may perturb gut ecology and metabolite output and surveys AI/ML frameworks for multi‐omics integration. Plant‐based, fiber‐rich dietary patterns generally enrich saccharolytic guilds, boost SCFAs production, and modulate bile acid signaling, whereas Westernized patterns favor bile‐tolerant, amino acid‐fermenting consortia and proinflammatory metabolites. Preclinical data suggest that incretin‐based therapies remodel the microbiome‐metabolome axis, but human causal mediation remains unproven and observed changes may partly reflect weight loss or metabolic improvement. Function‐centered metrics outperform phylum‐level ratios for translation. Harmonized longitudinal cohorts and explainable ML‐derived microbial and metabolomic signatures are now pivotal to identify responder subtypes and actionable microbe‐metabolite targets, enabling precision nutrition alongside pharmacotherapy across the lifespan.