Effects of chitooligosaccharides on the rebalance of gut microorganisms and their metabolites in patients with nonalcoholic fatty liver disease

Abstract Chitobiose (OC)and chitotriose (TOC)were used to simulate the in vitro fermentation of feces samples from nonalcoholic fatty liver disease (NAFLD) patients to evaluate their effects on gut microorganisms and metabolites. The results indicated that OC and TOC shifted the gut microbial community of NAFLD patients to that of healthy volunteers. Specifically, OC and TOC increased the relative abundance of Fusobacteria, while reducing Actinobacteria and the ratio of Firmicutes to Bacteroidetes. OC's targeted bacteria were Fusobacterium, Clostridium sensu stricto 13 and Parabacteroides, while TOC's targeted bacteria were Clostridium sensu stricto 1, Enterococcus. The content of total short-chain fatty acids, propionic acid and butyric acid in the OC and TOC groups increased significantly, which was closely related to the increase in the abundance of the targeted flora. Although the non-targeted metabolites of OC and TOC had a high degree of similarity in the positive ion mode and a large difference in the negative ion mode. The up-regulated metabolites of the OC and TOC groups include bile acids (7-ketodeoxycholic acid, docosahexaenoic acid ethyl ester, deoxycholic acid, cholic acid), amino acids (succinyl proline, cys-tyr, L-β-leucine), antibiotics (fortimicin FU-10, kanoamine), and down-regulated metabolites include xanthine, hypoxanthine, L-glutamic acid, acetophenone, etc. The biomarker metabolites of OC and TOC may reveal the probiotic effect on gut microecological health on the biosynthesis of amino acids, butyric and bile acid metabolism pathways. The results can be helpful for the further development of COS as a functional food.