Silent allies: non-living microbes shaping the future of cardiometabolic health

Abstract

Background: Metabolic syndrome and its components constitute significant global health challenges, and growing evidence links their development to gut microbiota disturbances and altered microbial metabolites. Postbiotics have emerged as promising alternatives to traditional probiotics, offering greater safety, stability, and mechanistic specificity. This review synthesizes current preclinical and clinical evidence on their potential roles in managing key cardiometabolic risk factors. Main body: For glucose homeostasis, preclinical studies (PS) demonstrate benefits in fasting glucose, HbA1c, glucose tolerance, and insulin sensitivity, though responses vary by strain, preparation method, and experimental model. Human studies indicate that metabolically at-risk individuals, particularly those with prediabetes, may benefit, while results in overweight, obese, or healthy populations are generally neutral. For obesity, PS consistently show that inactivated bacterial cells, heat-treated strains, and microbial metabolites reduce body weight, visceral adiposity, and adipose inflammation. Clinically, findings across human populations are inconsistent; however, interventions using postbiotic preparations derived from intact, inactivated microbial cells tend to produce more favorable effects on anthropometric indices than postbiotic formulations. For lipid disorders, in PS, postbiotics reduce triglycerides, total cholesterol, and LDL-C while increasing HDL-C. In clinical studies, short chain fatty acid-based postbiotics may improve lipid parameters, although their effectiveness depends on factors including metabolic status, age, dosage, and duration of supplementation. For hypertension, PS support reductions in blood pressure and improved vascular function, while human results vary, with some forms such as direct butyrate showing paradoxically increased blood pressure. Conclusions: Overall, postbiotics show considerable promise, but more rigorous clinical trials are needed to optimize formulations, dosing, and target populations.