Bacteroides salyersiae is a potent chondroitin sulfate-degrading species in the human gut microbiota.

Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS could not be absorbed after oral intake due to its polyanionic nature and large molecular weight. Gut microbiota has recently been proposed to play a pivotal role in the metabolism of drugs and nutrients. Nonetheless, how CS is degraded by the human gut microbiota has not been fully characterized. In the present study, we demonstrated that each human gut microbiota was characterized with a unique capability for CS degradation. Degradation and fermentation of CS by the human gut microbiota produced significant amounts of unsaturated CS oligosaccharides (CSOSs) and short-chain fatty acids. To uncover which microbes were responsible for CS degradation, we isolated a total of 586 bacterial strains with a potential CS-degrading capability from 23 human fecal samples. Bacteroides salyersiae was a potent species for CS degradation in the human gut microbiota and produced the highest amount of CSOSs as compared to other well-recognized CS-degraders, including Bacteroides finegoldii, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, and Bacteroides ovatus. Genomic analysis suggested that B. salyersiae was armed with multiple carbohydrate-active enzymes that could potentially degrade CS into CSOSs. By using a spent medium assay, we further demonstrated that the unsaturated tetrasaccharide (udp4) produced by the primary degrader B. salyersiae could serve as a "public goods" molecule for the growth of Bacteroides stercoris, a secondary CS-degrader that was proficient at fermenting CSOSs but not CS. Taken together, our study provides insights into the metabolism of CS by the human gut microbiota, which has promising implications for the development of medical and nutritional therapies for osteoarthritis. Video Abstract.

Polysaccharide from edible alga Gloiopeltis furcata attenuates intestinal mucosal damage by therapeutically remodeling the interactions between gut microbiota and mucin O-glycans.

Gloiopeltis furcata is an edible alga that has long been consumed in China. However, the bioactive polysaccharides from G. furcata have been largely unexplored. Here, we show for the first time that a sulfated polysaccharide from G. furcata (SAO) could improve the integrity of the colonic epithelial layer and protect against dextran sulfate sodium-induced intestinal mucosal damage. Mechanistically, SAO attenuated colonic mucosal damage by therapeutically remodeling the interactions between gut microbiota and mucin O-glycans. Specifically, SAO increased the proportions of complex long-chain mucin O-glycans in the epithelial layer with two terminal N-acetylneuraminic acid residues and promoted the growth of probiotic bacteria including Roseburia spp. and Muribaculaceae. Altogether, our study demonstrates a novel application of SAO for the treatment of inflammatory bowel disease-associated mucosal damage and forms the basis to understand the therapeutic effects of natural polysaccharides from the perspective of symbiotic interactions between host mucin O-glycome and gut microbiome.

Dietary Polysaccharide from Enteromorpha Clathrata Modulates Gut Microbiota and Promotes the Growth of Akkermansia muciniphila, Bifidobacterium spp. and Lactobacillus spp.

Recently, accumulating evidence has suggested that Enteromorpha clathrata polysaccharide (ECP) could contribute to the treatment of diseases. However, as a promising candidate for marine drug development, although ECP has been extensively studied, less consideration has been given to exploring its effect on gut microbiota. In this light, given the critical role of gut microbiota in health and disease, we investigated here the effect of ECP on gut microbiota using 16S rRNA high-throughput sequencing. As revealed by bioinformatic analyses, ECP considerably changed the structure of the gut microbiota and significantly promoted the growth of probiotic bacteria in C57BL/6J mice. However, interestingly, ECP exerted different effects on male and female microbiota. In females, ECP increased the abundances of Bifidobacterium spp. and Akkermansia muciniphila, a next-generation probiotic bacterium, whereas in males, ECP increased the population of Lactobacillus spp. Moreover, by shaping a more balanced structure of the microbiota, ECP remarkably reduced the antigen load from the gut in females. Altogether, our study demonstrates for the first time a prebiotic effect of ECP on gut microbiota and forms the basis for the development of ECP as a novel gut microbiota modulator for health promotion and disease management.

Structural modulation of gut microbiota by chondroitin sulfate and its oligosaccharide.

Chondroitin sulfate (CS) as a dietary supplement and a symptomatic slow acting (SYSA) drug has been used for years. Recently, CS has been demonstrated to be readily degraded and fermented in vitro by specific human gut microbes, hinting that dietary CS may pose a potential effect on gut microbiota composition in vivo. However, until now, little information is available on modulations of gut microbiota by CS. In the present study, modulations of gut microbiota in Kunming mice by CS and its oligosaccharide (CSO) were investigated by high-throughput sequencing. As evidenced by Heatmap and principal component analysis (PCA), the female microbiota were more vulnerable than the male microbiota to CS and CSO treatment. Besides, it is of interest to found that CS and CSO had differing effects on the abundance of Bacteroidales S24-7, Bacteroides, Helicobacter, Odoribacter, Prevotellaceae and Lactobacillus in male mice versus female mice. Collectively, we demonstrated a sex-dependent effect on gut microbiota of CS and CSO. In addition, since gut microbiota exerts a major effect on host physiology, our study highlighted that certain beneficial effects of CS may be associated with modulations of gut microbiota, which merits further investigation.

Degradation of chondroitin sulfate by the gut microbiota of Chinese individuals.

Oral preparations of chondroitin sulfate (CS) have long been used as anti-osteoarthritis (anti-OA) drugs. However, little is known about the degradation of CS by human gut microbiota. In the present study, degradation profiles of CSA (the main constituent of CS drugs) by the human gut microbiota from six healthy subjects were investigated. Each individual's microbiota had differing degradation activities, but ΔUA-GalNAc4S was the end product in all cases. To elucidate the mechanisms underlying this phenomenon, different CSA-degrading bacteria were isolated from each individual's microbiota and tested for CSA degradation. In addition to Bacteroides thetaiotaomicron J1, Bacteroides thetaiotaomicron 82 and Bacteroides ovatus E3, a new CSA-degrading bacterium, Clostridium hathewayi R4, was isolated and characterized. Interestingly, at least two different CSA-degrading species were identified from each individual's gut microbiota. Predictably, these functional bacteria also had differing degradation rates, but still generated the same end product, ΔUA-GalNAc4S. In addition, the human fecal isolates produced different degradation profiles for CSC, CSD, and CSE, suggesting that CS could be readily metabolized to varying extents by diverse microbial consortiums, which may help to explain the poor bioavailability and unequal efficacy of CS among individuals in OA treatment.