Dietary Polyphenols and Gut Microbiota Cross-Talk: Molecular and Therapeutic Perspectives for Cardiometabolic Disease: A Narrative Review

Abstract

The intricate interplay between the gut microbiota and polyphenols has emerged as a captivating frontier in understanding and potentially harnessing the therapeutic potential of these bioactive compounds. Phenolic compounds, renowned for their antioxidant, anti-inflammatory, antidiabetic, and anticancer properties, are subject to intricate transformations within the gut milieu, where the diverse microbial ecosystem exerts profound effects on their metabolism and bioavailability. Conversely, polyphenols exhibit a remarkable capacity to modulate the composition and activity of the gut microbiota, fostering a bidirectional relationship that extends beyond mere nutrient processing. This symbiotic interaction holds significant implications for human health, particularly in cardiometabolic diseases such as diabetes mellitus, metabolic-dysfunction-associated steatotic liver disease, and cardiovascular disease. Through a comprehensive exploration of molecular interactions, this narrative review elucidates the reciprocal dynamics between the gut microbiota and polyphenols, unveiling novel avenues for therapeutic intervention in cardiometabolic disorders. By unravelling the intricate cross-talk between these two entities, this review underscores the multifaceted roles of polyphenols in overall health and the pivotal role of gut microbiota modulation as a promising therapeutic strategy in mitigating the burden of cardiometabolic diseases.

Keywords: cardiovascular disease; diabetes mellitus; flavonoids; gut microbiota; polyphenols; steatotic liver disease.

Figure 1

Impact of phenolic compounds on gut microbiota composition and function. Phenolic compounds are bioactive molecules capable of inducing numerous beneficial effects in our organism by modulating the gut microbiota composition. These compounds exert a positive modulation through two main mechanisms: 1. A prebiotic effect, promoting the growth and production of beneficial bacteria and consequently increasing the levels of short-chain fatty acids. 2. An antimicrobial effect, suppressing pathogenic bacteria by altering their structural and functional integrity through the inhibition of PBP2 and PBP4, leading to reduced peptidoglycan cross-linking and increased lysine content as well as creating an acidic microenvironment by proton donation, impairment of proton pumps, and depletion of H+-ATPase5.

Figure 2

Therapeutic targets in MASLD. This illustration highlights the role of phenolic compounds in addressing metabolic-associated fatty liver disease (MASLD). These compounds modulate key pathways, including NF-κB, AMPK, and PPARs, to reduce lipid accumulation, insulin resistance, oxidative stress, and inflammation. By activating PPARs, they offer an alternative to conventional treatments. Phenolic compounds target diverse signaling pathways, providing therapeutic potential within the cardiometabolic context and reshaping MASLD management. TLRs: toll-like receptor; AMPK: AMP-activated protein kinase; JAK/STAT: Janus kinase/signal transducers and activators of transcription; PI3K/Akt: phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT); SREBP-1c: sterol regulatory element binding protein-1c; PPARs: peroxisome proliferator-activated receptors; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; TNF-α: tumor necrosis factor alpha; IL-6: interleukin-6.