Research progress in molecular mechanisms of lipid metabolism regulation by natural active components through targeting the gut microbiota

Abstract:

Lipid metabolism disorders have emerged as a global health challenge, and gut microbiota dysbiosis, along with the consequent metabolic endotoxemia, are key factors promoting this pathological process. This review summarizes the molecular mechanisms by which natural active components (NACs) improve lipid homeostasis through targeted modulation of gut microecology. At the microecological intervention level, NACs optimize the microbiota structure by increasing the abundance of functional bacteria such as Bifidobacterium and Akkermansia muciniphila, while inhibiting the proliferation of opportunistic pathogens like Desulfovibrio. At the “metabolite-host” interaction level, the lipid-lowering mechanisms mainly involve two aspects. The first is the targeted effects of metabolites, wherein short-chain fatty acids, secondary bile acids, and phenolic acid derivatives specifically modulate metabolic targets including 3-hydroxy-3-methylglutaryl-coenzyme A reductase and fatty acid synthase. The second is the host signaling responses, wherein the aforementioned metabolic mediators synergistically modulate key signaling nodes, such as adenosine 5′-monophosphate-activated protein kinase (AMPK)/sterol regulatory element-binding protein-1c (SREBP-1c) and peroxisome proliferator-activated receptors (PPARs), to inhibit de novo lipogenesis and promote fatty acid β-oxidation, while simultaneously inhibiting the Toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) pathway to alleviate inflammation-associated abnormal lipid deposition. The “component-microbiota-metabolite-host signaling” regulatory mechanism outlined herein provides a theoretical reference for elucidating the pharmacodynamic material basis of NACs and developing gut microecology-based personalized nutritional intervention strategies.