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

TL;DR

Three molecular weight fractions of water-soluble lentinan demonstrated Mw-gradient-dependent regulation of gut microbiota from healthy and obese individuals, with lower molecular weight fractions showing distinct prebiotic effects including progressive reduction in Firmicutes/Bacteroidetes ratio as Mw decreased.

Key Findings

Three molecular weight fractions of water-soluble lentinan (WSL) were successfully derived from Lentinula edodes with distinct molecular weights.

  • WSL-40 had a molecular weight of 2.19 × 10^6 Da
  • WSL-60 had a molecular weight of 2.96 × 10^5 Da
  • WSL-80 had a molecular weight of 1.70 × 10^4 Da
  • Fractions were derived from Lentinula edodes cultivated in Zhejiang
  • Fractions were investigated using an in vitro fermentation model

WSL-80 reached total sugar glycolysis equilibrium the earliest and produced the maximal butyric acid among the fractions in healthy microbiota.

  • WSL-80 is the lowest molecular weight fraction at 1.70 × 10^4 Da
  • Maximal butyric acid production was observed with WSL-80 in healthy microbiota
  • These effects were characterized as Mw-dependent regulation
  • Results were observed using an in vitro fermentation model with healthy individual microbiota

WSL-80 specifically promoted the growth of Parabacteroides in healthy microbiota.

  • The effect was statistically significant (p < 0.05)
  • This promotion was specific to WSL-80, the lowest molecular weight fraction
  • This was observed in the healthy microbiota fermentation model
  • WSL demonstrated diet-induced obesity prevention potential through this Mw-dependent regulation

In obese microbiota, WSL fractions alleviated dysbiosis and enhanced proliferation of beneficial genera with Mw-gradient-dependent effects.

  • A progressive reduction in the Firmicutes/Bacteroidetes ratio was observed as Mw decreased
  • All three WSL fractions demonstrated effects on obese microbiota
  • The effects were characterized as showing an 'Mw-gradient-dependent' pattern
  • Results were obtained using an in vitro fermentation model with obese individual microbiota

WSL-80 was associated with higher abundances of Phascolarctobacterium, Klebsiella, and Parabacteroides in obese microbiota.

  • WSL-80 is the lowest molecular weight fraction (1.70 × 10^4 Da)
  • Three distinct genera showed higher abundance with WSL-80 treatment in obese microbiota
  • These effects were observed in the in vitro fermentation model using obese individual microbiota
  • Parabacteroides was promoted by WSL-80 in both healthy and obese microbiota

Elevated Bacteroides abundance was specifically noted with WSL-60 and WSL-80 fractions in obese microbiota.

  • Bacteroides elevation was observed with both medium (WSL-60, 2.96 × 10^5 Da) and low (WSL-80, 1.70 × 10^4 Da) molecular weight fractions
  • This effect was not reported for the highest molecular weight fraction WSL-40
  • Results were from the in vitro fermentation model with obese microbiota

Maximal Weissella abundance was observed with WSL-40, the highest molecular weight fraction, in obese microbiota.

  • WSL-40 has the highest molecular weight at 2.19 × 10^6 Da
  • Weissella promotion appeared specific to the highest molecular weight fraction
  • This contrasts with other beneficial genera that were more promoted by lower Mw fractions
  • Results suggest different molecular weight fractions selectively promote different beneficial bacterial genera

Lentinan molecular weight gradient functions as a directional regulator of functional microbiota composition.

  • Different Mw fractions selectively promoted distinct microbial genera in both healthy and obese microbiota
  • The study establishes a theoretical basis for precision nutrition interventions against obesity
  • The Mw-gradient effects were demonstrated across both healthy and obese microbiota contexts
  • Authors describe this as establishing 'lentinan's Mw gradient as a directional regulator of functional microbiota'

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Citation

Yan X, Shen Y, Tao Q, Shi P, Zhang Q, Qi Y, et al.. (2026). Molecular weight-engineered lentinan fractions as prebiotic modulators: Steering gut microbiota for precision obesity intervention.. Food research international (Ottawa, Ont.). https://doi.org/10.1016/j.foodres.2025.118169