A Multi-Component High-Fibre Meal Replacement Containing Pyrus bretschneideri Rehd. Pomace Alleviates Diet-Induced Obesity by Modulating the Gut Microbiota, Bile Acid Metabolism and Hepatic AMPK Signalling.

This study employed an integrated multi-omics approach to investigate the regulatory effects and molecular mechanisms of a multi-component, high-dietary-fibre meal replacement powder containing Pyrus bretschneideri Rehd. pomace (PDMR) in high-fat-diet-induced obese mice. The results showed that PDMR significantly reduced body weight gain, Lee's index, serum lipid and inflammatory cytokine levels, and improved adipocyte morphology. Mechanistically, PDMR activated the AMPK signalling pathway, suppressed lipogenesis via the ACC-SREBP1c-FAS axis, and promoted fatty acid β-oxidation and thermogenesis through the PPARα-CPT-1 and PGC-1α/UCP-1 axes. Moreover, PDMR remodelled the gut microbiota by enriching bacteria associated with SCFA production and anti-inflammatory activity (Alloprevotella, Ruminococcaceae, Odoribacter and Prevotellaceae_Ga6A1_group) and inhibiting bacteria associated with pro-inflammatory and fat-accumulation effects (Candidatus Saccharimonas and Clostridia_UCG-014), whilst reversing the excessive accumulation of secondary bile acids. Correlation analysis established a multi-level regulatory network linking gut microbiota, secondary bile acid metabolites and AMPK target gene expression. Collectively, PDMR may ameliorate lipid metabolic disorders through a potential gut microbiota-secondary bile acid-AMPK axis, providing a scientific basis for the high-value utilisation of Pyrus bretschneideri Rehd. and the development of functional meal replacement foods.