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.