Microbiome‐modulating nutraceuticals ameliorate dyslipidemia in type 2 diabetes: A systematic review, meta‐analysis, and meta‐regression of clinical trials

Abstract Aims Type 2 Diabetes is intrinsically linked to cardiovascular disease (CVD) via diabetic dyslipidemia, both of which remain global health concerns with annually increasing prevalence. Given the established links between gut microbiome dysbiosis and metabolic diseases, its modulation is an attractive target to ameliorate metabolic imbalances in such patients. There is a need to quantitively summarise, analyse, and describe future directions in this field. Methods We conducted a systematic review, meta‐analysis, and meta‐regression following searches in major scientific databases for clinical trials investigating the effect of pro/pre/synbiotics on lipid profile published until April 2022. Data were pooled using random‐effects meta‐analysis and reported as mean differences with 95% confidence intervals (CIs). PROSPERO No. CRD42022348525. Results Data from 47 trial comparisons across 42 studies ( n = 2692) revealed that, compared to placebo/control groups, the administration of pro/pre/synbiotics was associated with statistically significant changes in total cholesterol (−9.97 mg/dL [95% CI: −15.08; −4.87], p < 0.0001), low‐density lipoprotein (−6.29 mg/dL [95% CI: −9.25; −3.33], p < 0.0001), high‐density lipoprotein (+3.21 mg/dL [95% CI: 2.20; 4.22], p < 0.0001), very‐low‐density lipoprotein (−4.52 mg/dL [95% CI: −6.36; −2.67], p < 0.0001) and triglyceride (−22.93 mg/dL [95% CI: −33.99; −11.87], p < 0.001). These results are influenced by patient characteristics such as age or baseline BMI, and intervention characteristics such as dosage and duration. Conclusions Our study shows that adjunct supplementation with a subset of pro/pre/synbiotics ameliorates dyslipidemia in diabetic individuals and has the potential to reduce CVD risk. However, widespread inter‐study heterogeneity and the presence of several unknown confounders limit their adoption in clinical practice; future trials should be designed with these in mind.