Bioactive compounds as therapeutic modulators of metabolic syndrome: targeting inflammation and gut microbiota regulation

Abstract

Food bioactives, including polyphenols, flavonoids, omega-3 fatty acids, and glucosinolates, play a crucial role in preventing metabolic syndrome by modulating chronic inflammation, gut microbiota homeostasis, and metabolic processes. These compounds influence key molecular pathways implicated in metabolic dysfunction and systemic inflammation. This review explores the mechanisms through which food bioactives contribute to metabolic health, emphasizing their role in inflammation regulation, gut microbiota modulation, and insulin sensitivity. A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science. Relevant peer-reviewed articles, meta-analyses, and clinical trials published in the last two decades were analyzed, focusing on bioactives’ biochemical actions and therapeutic potential in Metabolic syndrome. The study showed that bioactives mitigate inflammation by inhibiting NF-κB signaling and NLRP3 inflammasome activation, reducing pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). They also modulate gut microbiota, promoting beneficial bacteria (e.g., Akkermansia muciniphila ) and enhancing gut barrier integrity via increased expression of tight junction proteins. Short-chain fatty acids (SCFAs) derived from microbial metabolism contribute to systemic anti-inflammatory effects. Clinical studies indicate that polyphenol-rich diets, such as the Mediterranean diet, improve metabolic syndrome parameters by lowering inflammatory markers, enhancing lipid profiles, and improving insulin sensitivity. Despite promising findings, challenges such as poor bioavailability and variability in gut microbiome responses hinder clinical application. Strategies like nanoencapsulation and microbiome-targeted nutrition may optimize bioactive efficacy. Overall, food bioactives represent a promising strategy for metabolic health. Future research should focus on enhancing bioavailability, personalized nutrition, and large-scale clinical trials to establish optimal dosing and long-term benefits.