Phyllanthus emblica Polysaccharide Improves Metabolic Associated Fatty Liver Disease by Regulating Gut–Liver Axis through Akkermansia and Short-Chain Fatty Acid Receptors

Abstract

This study investigated the therapeutic effects of PEP-2, a 348.45 kDa pectin isolated from Phyllanthus emblica, against metabolic-associated fatty liver disease (MAFLD). Characterized as a homogalacturonan with minor rhamnogalacturonan I, PEP-2 consists of galacturonic acid, galactose, rhamnose, and arabinose. In high-fat diet-induced mice, PEP-2 significantly improved metabolic phenotypes, reducing obesity, insulin resistance, and hepatic steatosis. Mechanistically, PEP-2 modulated the gut–liver axis by enriching Akkermansia and enhancing short-chain fatty acid (SCFA) production. These changes were associated with increased colonic mRNA expression of SCFA receptor-related genes, including GPR41, GPR43, and GPR109A, and favorable regulation of hepatic lipid metabolism-related genes, including AMPK, PPARα, and CPT1. In vitro, PEP-2 promoted Akkermansia muciniphila growth, while its fermentation products effectively reduced lipid accumulation in cell models. These findings support a microbiota-SCFA-associated mechanism underlying the beneficial effects of PEP-2 and highlight its potential as a prebiotic candidate for functional food development against metabolic disorders.