Structure-function relationship of polysaccharides derived from Pericarpium Citri Reticulatae 'Chachiensis' : highlighting the effects on metabolic syndrome by regulating gut microbiota

Abstract

The precise interaction between gut microbes and dietary polysaccharides is not fully understood. This study elucidated the structure-function relationship and the underlying mechanisms of polysaccharides derived from Pericarpium Citri Reticulatae ‘Chachiensis’ (PCRCP) against a high-fat diet (HFD)-induced metabolic syndrome (MetS). Three subfractions (PCRCPI-III) were isolated, with GalA contents of 79.7%, 56.7%, and 33.5% and average molecular weights of 48.85, 32.28, and 51.12 kDa, respectively. Notably, PCRCPI exhibits a linear backbone composed of →4)-GalA-(1→ residues, complemented by side chains of →5)-Ara-(1→ and →4)-Gal-(1→, interconnected via →2,4)-Rha-(1→ linkages. Their efficacy in mitigating MetS was structure-dependent, with PCRCPI exerting the most significant therapeutic effects. Oral administration of PCRCPI in mice alleviated metabolic phenotypes in a gut microbiota-dependent manner, characterized by the selective enrichment of an elongation taxonomic chain Lactobacillales - Lactobacillaceae - Lactobacillus - Lactobacillus spp. Colonization with live Lactobacillus strains enhanced the efficacy of PCRCPI in improving metabolic phenotypes, especially when co-administered with Lactobacillus murinus , which synergistically augmented insulin sensitivity and activated hepatic PPAR signaling. Additionally, PCRCPI increased microbial-derived deoxycholic acid, which activated PPAR-mediated fatty acid oxidation in hepatocytes. These findings suggest that PCRCPI may serve as a promising therapeutic agent for MetS management, potentially through the targeted stimulation of beneficia Lactobacillus proliferation.