Recently, researchers from Chinese Food Processing and Equipment Innovation Team at the Institute of Food Science and Technology, Chinese Academy of Agricultural Sciences (IFST-CAAS), systematically elucidated the in vitro fermentation characteristics of structurally distinct low molecular weight chondroitin sulfates (LMCSs). The research findings were published on International Journal of Biological Macromolecules (JCR Q1, IF=7.7). Wang Kangyu, a PhD student, is the first author, Prof. Zhang Chunhui and Dr. Guo Yujie are co-corresponding authors. The research was supported by the National Key R&D Program of China (2021YFD2100804), and National Agricultural Science and Technology Innovation Project (CAAS-ASTIP-2024).

Previous studies have shown that the composition of gut microbiota and the activity of their metabolic products are closely related to the molecular structure of dietary polysaccharides. Chondroitin sulfate (CS) is a functional anionic polysaccharide with various biological activities, including anti-inflammatory and antioxidant effects. Its molecular weight can be reduced through hydrolysis, hydrogen abstraction, and deamination reactions to produce LMCSs with distinct structural characteristics. In this paper, structurally diverse LMCSs with the same molecular weight were prepared by oxidative degradation (LMCSO), deamidation cleavage (LMCSD), and hydrothermal depolymerization (LMCSH), and their fermentation dynamics were studied using in vitro models. Our aim was to elucidate the specific changes in gut microbiota and metabolites resulting from the structural differences between CS and LMCSs, and to reveal the polysaccharide structure-function activity pattern, which is crucial for the exploitation of LMCSs.

Studies have shown that oxidative, deamination, and hydrothermal depolymerization can reduce the molecular weight of CS to produce LMCSs with different structures. In vitro fermentation studies have shown that LMCSs with different structures exert distinct effects on the composition of gut microbiota and their metabolic products. The degree of carbohydrate metabolism was in the order of CS > LMCSH > LMCSO > LMCSD. Significantly, GlcA in chondroitin-6-sulfate (CSC) was more readily utilized by gut microbiota during fermentation, and this trend was more pronounced in LMCSs. The LMCSs group notably increased microbial richness and evenness, especially in the LMCSD group. Bacteroides fragilis was identified as a potential primary degrader of CS and LMCSs through species-level analysis. The abundance of Escherichia-Shigella was reduced by LMCSs, and short-chain fatty acids production was enhanced, particularly by LMCSO, while the production of beneficial metabolites such as N-acetyl-D-Glucosamine 6-Phosphate (GlcNAc-6P), lactate, and progesterone was stimulated. Among these, the metabolism of the key metabolite GlcNAc-6P was significantly and positively correlated with the abundance of Bacteroides, Clostridium_sensu_stricto_1, and Parabacteroides. 

Exploring the mechanisms by which gut microbiota metabolize LMCSs with different structures can provide theoretical support for the targeted preparation of LMCSs that modulate the gut microbiota.

https://doi.org/10.1016/j.ijbiomac.2025.143051

In vitro fermentation characteristics of structurally distinct LMCSs