Systematic analysis reveals that obesity involves a specific microbial signature: depletion of short-chain fatty acid-producing bacteria coupled with impaired gut hormone release through disrupted free fatty acid receptor signaling. This represents a concrete mechanism linking the gut microbiome to metabolic dysfunction beyond simple correlation. The therapeutic landscape shows a stark divide in efficacy. GLP-1 receptor agonists demonstrate substantial weight loss, while microbiota-targeted interventions like probiotics, prebiotics, and fecal transplants show only modest, variable effects in humans. This disparity highlights a critical gap between mechanistic promise and clinical reality for microbiome therapies. The finding suggests obesity treatment may require a precision medicine approach combining pharmaceutical hormone modulation with targeted microbiome restoration. However, the review's reliance on associative rather than causal evidence limits definitive conclusions about whether microbial changes drive obesity or result from it. This represents confirmatory rather than paradigm-shifting research, consolidating existing knowledge while pointing toward personalized multi-modal treatments that address both hormonal and microbial dysfunction simultaneously.