Gut Microbiota Modulation in Type 2 Diabetes and Cardiometabolic Risk: A Systematic Review

Cardiometabolic complications related to type 2 diabetes mellitus (T2DM) are often due to changes in the gut microbiota. The review analyzed studies looking at the effects of probiotics, prebiotics, high-fiber diets, and fecal microbiota transplantation (FMT) on glucose levels and heart and metabolic health in individuals either having T2DM or being at risk. The review followed the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines. The literature was searched using text terms and controlled vocabulary, employing Boolean operators "AND," "OR," and various combinations across PubMed, Embase, and the Cochrane Library. Open-access, full-text English papers from 2005 to 2025, including those authored by people, were searched. The quality was assessed using the Risk of Bias 2.0 (RoB 2.0) tool, and the evidence was appraised using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Fifteen randomized controlled trials (RCTs) were analyzed for methodological quality, with three categorized as having a high risk of bias (RoB). The GRADE tool categorized two high RoB RCTs as "low quality." However, two RCTs had low RoB and were classified as "high quality." Ten RCTs had uncertain RoB, lowering the evidence by one point to "moderate quality." A comprehensive review of RCTs was conducted to assess outcomes related to glycemic parameters (e.g., glycated hemoglobin (HbA1c), fasting glucose), lipid profiles, inflammatory markers, anthropometric measures, and gut microbiota composition. Interventions included probiotic and prebiotic supplementation, high-fiber or Mediterranean-style diets, and FMT. Probiotic yogurt containing Lactobacillus acidophilus and Bifidobacterium lactis significantly improved lipid profiles by reducing low-density lipoprotein cholesterol (LDL-C) and total cholesterol. High-fiber diets consistently lowered fasting blood glucose, HbA1c, triglycerides, and LDL-C while elevating high-density lipoprotein cholesterol (HDL-C) and beneficial short-chain fatty acid (SCFA)-producing bacteria. Anti-inflammatory effects were observed across interventions, notably with probiotics and polyphenol-rich Mediterranean diets, which reduced tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and other inflammatory cytokines. The Green-Mediterranean diet significantly improved weight, insulin resistance, and Framingham risk scores. Novel mechanisms involving SCFAs and bile acid metabolism were also identified as key modulators of host metabolic response. Microbiota-based interventions offer promising avenues for glycemic control and cardiometabolic risk reduction in patients with T2DM.