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

Abstract

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. 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. 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). Sixty-seven studies were included. Non-surgical interventions were associated with reduced TMAO (n = 8 studies; SMD: -0.56; 95% CI -0.90 to -0.22; I² = 74.7%), but not LPS (n = 10 studies; SMD: -0.11; 95% CI -0.58 to 0.35; I² = 91.2%). Surgical interventions were associated with decreased LPS (n = 7 studies; SMD: -0.47; 95% CI -0.80 to -0.14; I² = 78.8%), and increased TMAO (n = 8 studies; SMD: 0.49; 95% CI 0.08 to 0.90; I² = 81.8%) and secondary bile acids (n = 13 studies; SMD: 0.48; 95% CI 0.30 to 0.66; I² = 58.8%). Evidence on SCFAs and indole derivatives was limited. 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.