Postbiotics as Antiinflammatory and Immune-Modulating Bioactive Compounds in Metabolic Dysfunction-Associated Steatotic Liver Disease

Abstract

Postbiotics, defined as products or metabolic byproducts secreted by live bacteria or released after bacterial lysis, are emerging as promising therapeutic agents for metabolic dysfunction-associated steatotic liver disease (MASLD). This review explores the antiinflammatory and immunomodulatory properties of various postbiotics, including exopolysaccharides, lipoteichoic acid, short-chain fatty acids, hydrogen sulfide, polyamines, tryptophan derivatives, and polyphenol metabolites. These compounds have demonstrated potential in mitigating steatotic liver infiltration, reducing inflammation, and slowing fibrosis progression in preclinical studies. Notably, postbiotics exert their beneficial effects by modulating gut microbiota composition, enhancing intestinal barrier function, optimizing lipid metabolism, reducing hepatic inflammation and steatosis, and exhibiting hepatoprotective properties. However, translating these findings into clinical practice requires well-designed trials to validate efficacy and safety, standardize production and characterization, and explore personalized approaches and synergistic effects with other therapeutic modalities. Despite challenges, the unique biological properties of postbiotics, such as enhanced safety compared to probiotics, make them attractive candidates for developing novel nutritional interventions targeting the multifactorial pathogenesis of MASLD. Further research is needed to establish their clinical utility and potential to improve liver and systemic outcomes in this increasingly prevalent condition.

Keywords: gut microbiota; immunomodulation; inflammation; metabolic dysfunction‐associated steatotic liver disease; nutritional interventions; postbiotics.