Weight loss diet co-supplemented with biotics improved leptin levels in overweight and obese adults: A systematic review and meta-analysis

Abstract

Background and aim Evidence from clinical trials regarding the potential interactive effects of combining weight loss diets with microbiota-targeted interventions on adipokine levels remains inconsistent. Therefore, to address this knowledge gap, we performed a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the combined effects of calorie restriction and microbiota-targeted interventions on adiponectin and leptin levels, in comparison with calorie-restricted diets alone, in adults. Methods A systematic literature search was conducted across three major electronic databases, Web of Science (ISI), PubMed, and Scopus, up to February 2025, without any restrictions on publication date or language to identify relevant RCTs. A random-effects model was applied to calculate pooled weighted mean differences (WMDs) along with 95 confidence intervals. Results Meta-analysis of data from six trials (n = 510) revealed no significant effect on circulating adiponectin concentrations (WMD: 1.89 & micro;g/mL; 95 CI: -0.14-3.93; P = 0.068; I & sup2; = 64.2; P-Heterogeneity=0.010) following supplementation with probiotics, prebiotics, or synbiotics combined with a calorie-restricted diet, compared to a calorie-restricted diet alone. In contrast, meta-analysis of nine trials involving 653 participants showed a significant decrease in circulating leptin levels (WMD: -10.79 ng/mL; 95 CI: -17.85 to -3.73; P = 0.003; I & sup2; = 69.1; P-Heterogeneity=0.001). For adiponectin concentration, significant increases were observed in subgroup analyses of studies conducted outside Asia (WMD: 1.38 & micro;g/mL; 95 CI: 0.52-2.24; P = 0.002) and studies using probiotics as the intervention (WMD: 1.51 & micro;g/mL; 95 CI: 0.61-2.41; P = 0.001). The subsequent subgroup analyses revealed that the leptin-lowering effect was particularly pronounced in studies conducted in Asia (WMD: -19.59 ng/mL; 95 CI: -26.80 to -12.38; P < 0.001); in studies using prebiotics (WMD: -15.34 ng/mL; 95 CI: -28.57 to -2.10; P = 0.023) or probiotics (WMD: -10.58 ng/mL; 95 CI: -19.23 to -1.93; P = 0.016) as interventions; in studies recruiting younger participants (<50 years: WMD: -13.48 ng/mL; 95 CI: -24.97 to -1.99; P = 0.021) and older participants (>= 50 years: WMD: -6.92 ng/mL; 95 CI: -12.57 to -1.27; P = 0.016); and in studies incorporating an exercise component (WMD: -17.96 ng/mL; 95 CI: -25.02 to -10.89; P < 0.001). Despite these findings, the overall certainty of the evidence was rated as low. Conclusion Our findings indicate that adding probiotics, prebiotics, or synbiotics to calorie-restricted diets significantly lowers leptin levels, while effects on adiponectin remain uncertain. However, these effects may vary by region, intervention type, age, and exercise. Given the low certainty of evidence, well-designed, long-term RCTs are needed to confirm these results<bold>.</bold>