Effects of Weight Loss Interventions on Gut Microbiota-Derived Metabolites Linked to Cardiometabolic Health: A Systematic Review and Meta-Analysis.

BACKGROUND: Gut microbiota-derived metabolites are emerging as potential mediators between obesity and cardiometabolic conditions. While weight loss interventions modify microbiota composition, their effects on systemic microbial metabolites remain unclear. OBJECTIVE: To evaluate the effect of weight loss interventions on circulating levels of key gut-derived metabolites in individuals with overweight or obesity, through a systematic review and meta-analysis. METHODS: Searches were performed in MEDLINE, EMBASE, and The Cochrane Library up to July 17, 2024. We included intervention studies in individuals with overweight/obesity undergoing weight loss strategies, with measurement of serum lipopolysaccharides (LPSs), trimethylamine N-oxide (TMAO), secondary bile acids, short-chain fatty acids (SCFAs), or indole derivatives. Meta-analysis used the standardized mean difference (SMD) with a random-effects model, stratified by intervention type (non-surgical or surgical). RESULTS: = 58.8%). Evidence on SCFAs and indole derivatives was limited. CONCLUSION: Weight loss strategies have distinct effects on gut microbiota-derived metabolites, underscoring the complexity of microbiota-host interactions and the potential for personalized approaches to obesity treatment.