Galactooligosaccharide or 2′-Fucosyllactose Modulates Gut Microbiota and Inhibits LPS/TLR4/NF-κB Signaling Pathway to Prevent DSS-Induced Colitis Aggravated by a High-Fructose Diet in Mice

• Published in: Journal of agricultural and food chemistry 2023-06, Vol.71 (24), p.9349-9360
• Main Authors: Chen, Tao, Wang, Chuqing, Nie, Chenxi, Yuan, Xiaojin, Tu, Aobai, Li, Juxiu
• Format: Article
• Language: English
• Subjects: Animals; Bioactive Constituents, Metabolites, and Functions; Colitis - chemically induced; Colitis - drug therapy; Colitis - genetics; Colon; Dextran Sulfate - adverse effects; Diet; Disease Models, Animal; Fructose; Gastrointestinal Microbiome; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; NF-kappa B - genetics; Signal Transduction; Toll-Like Receptor 4 - genetics
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/acs.jafc.2c08814

A high-fructose diet (HFrD) has been reported to exacerbate dextran sulfate sodium (DSS)-induced colitis. 2′-Fucosyllactose (FL) and galactooligosaccharide (GOS) have been shown, respectively, to have preventive and ameliorative effects on colitis, while limited research has explored whether GOS and FL may be equally protective or preventive in mice with HFrD. Here, we evaluated the protective effects of FL and GOS on colitis exacerbated by feeding HFrD and explored the underlying mechanisms. DSS-induced colitis was studied in four randomized C57BL/6J male mice (n = 8 mice/group). Among them, three groups were fed with HFrD, and two received either GOS or FL treatment, respectively. Gut microbial composition was analyzed by 16S rDNA gene sequencing. Intestinal barrier integrity and inflammatory pathway expression were measured using qPCR, immunofluorescence, and Western blot methods. Compared to the HFrD group, GOS or FL treatment increased the α-diversity of the gut microbiota, reduced the relative abundance of Akkermansia, and increased the content of short-chain fatty acids (SCFAs), respectively. Compared with the HFrD group, GOS or FL treatment improved the loss of goblet cells and the reduction of tight junction protein expression, thereby improving intestinal barrier integrity. Also, GOS or FL inhibited the LPS/TLR4/NF-κB signaling pathway and oxidative stress to suppress the inflammatory cascade compared with the HFrD group. These findings suggest that GOS or FL intake can alleviate HFrD-exacerbated colitis, with no significant difference observed between GOS and FL treatments.