Obesity is intricately associated with the gut microbiome, and emerging research suggests that lifestyle interventions, such as dietary changes and active lifestyle, can significantly affect the composition and function of the gut microbiome. However, evidence demonstrating a causal link between these changes and long-term weight loss or metabolic improvements remains limited. This systematic review investigates how overweight- and obesity-targeted interventions, such as dietary modifications, physical activity, supplementation with prebiotics and probiotics, and fecal microbiota transplantation (FMT), manipulate gut microbiome diversity and composition, major metabolites, and weight status. We conducted a systematic literature search and included 87 out of 255 randomized clinical trials with 6086 adults aged 18-84 with a BMI ≥ 25 kg/m. The quality of the included RCTs ranged from very low to moderate risk of bias. Most interventions did not cause any significant changes in microbial alpha or beta diversity, however, positive associations between prebiotic consumption and abundance of Actinobacteria and Bifidobacterium were observed, and intake of probiotics was related to increased levels of Lactobacillus and reduced body weight and body fat. We did not observe strong evidence for associations between SCFA levels, gut microbiome, and obesity. Overall, diversity and heterogeneity in reported outcomes, both in methods and results, were large. Taken together, our findings suggest that overweight- and obesity-targeted dietary interventions of at least 4 weeks, particularly those involving prebiotics and probiotics, have the potential to beneficially alter the gut microbiome, although standardized protocols and harmonized reporting are needed to confirm this through meta-analysis. 2
