Abstract
Chondroitin sulfate (CS) has been widely used for medical and nutraceutical purposes due to its roles in maintaining tissue structural integrity. We investigated if CS disaccharides may act as a bioactive compound and modulate gut microbial composition in mice. Our data show that CS disaccharides supplementation for 16 days significantly reduced blood LPS in the mice experiencing exhaustive exercise stress. CS disaccharides partially restored total fecal short-chain fatty acids from the level significantly repressed in mice under the stress. Our findings demonstrated that CS was likely butyrogenic and resulted in a significant increase in fecal butyrate concentration. CS disaccharides had a profound impact on gut microbial composition, affecting the abundance of 13.6% and 7.3% Operational Taxonomic Units in fecal microbial communities in healthy and stressed mice, respectively. CS disaccharides reduced the prevalence of inflammatory Proteobacteria. Together, our findings demonstrated that CS may ameliorate stress-induced intestinal inflammation. Furthermore, CS significantly increased intestinal Bacteroides acidifaciens population, indirectly exerting its immunomodulatory effect on the intestine. CS disaccharides had a significant impact on a broad range of biological pathways under stressed condition, such as ABC transporters, two-component systems, and carbohydrate metabolism. Our results will facilitate the development of CS as a bioactive nutraceutical.
Highlights
Chondroitin sulfate (CS) belongs to a class of sulfated glycosaminoglycans (GAG) that consist of up to hundreds of repeating disaccharide units
One day after exhaustive exercise, the mice had a significant reduction in feed intake (P < 0.01)
Exercise is known to have an important impact on the microbial diversity and composition of the gut microbiome[22, 23]
Summary
Chondroitin sulfate (CS) belongs to a class of sulfated glycosaminoglycans (GAG) that consist of up to hundreds of repeating disaccharide units. Gene knockout studies suggest that CS plays a critical role in development and homeostasis of organs and tissues[3]. CS can be readily metabolized to component disaccharides in the hindgut, suggesting a role by the gut microbiome[13]. The β-glucuronidase activities can be detected in a broad range of bacteria, including those from the most predominant phyla in the gut microbiome, such as Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria, suggesting that many CS disaccharides-degrading bacteria have yet to be discovered. Stress-induced fatigue has been linked to alterations in the gut microbiome[19]. We attempted to understand potential prebiotic effect of CS disaccharides and their role in modulating the structure and function of the gut microbiome under healthy and exhaustive exercise-induced stressed conditions using a murine model
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