Molecular weight-engineered lentinan fractions as prebiotic modulators: Steering gut microbiota for precision obesity...

Lentinus edodes polysaccharides are widely recognized for their potential contributions to human health, in part due to their interactions with the gut microbiota. In this study, three molecular weight (Mw) fractions of water-soluble lentinan (WSL)-WSL-40 (2.19 × 10⁶ Da), WSL-60 (2.96 × 10⁵ Da), and WSL-80 (1.70 × 10⁴ Da), derived from Lentinula edodes cultivated in Zhejiang, were systematically investigated using an in vitro fermentation model to assess their regulatory effects on gut microbiota from healthy and obese individuals. In healthy microbiota, WSL demonstrated diet-induced obesity prevention potential via Mw-dependent regulation: WSL-80 reached a total sugar glycolysis equilibrium the earliest, with maximal butyric acid production, and specifically promoted the growth of Parabacteroides (p < 0.05). In obese microbiota, WSL alleviated dysbiosis and enhanced the proliferation of beneficial genera, with Mw-gradient-dependent effects demonstrated by a progressive reduction in the Firmicutes/Bacteroidetes ratio as Mw decreased. Higher abundances of Phascolarctobacterium, Klebsiella, and Parabacteroides were observed with WSL-80. Elevated Bacteroides were noted in WSL-60 and WSL-80, and maximal Weissella abundance was observed in WSL-40. This establishes lentinan's Mw gradient as a directional regulator of functional microbiota, thereby providing a theoretical basis for precision nutrition interventions against obesity.