Journal Article

2′-Fucosyllactose Remits Colitis-Induced Liver Oxygen Stress through the Gut–Liver–Metabolites Axis

Gao, Yanan, Fan, Linlin, Wang, Jiaqi, Zheng, Nan, Yao, Qianqian

2022

Overview

Liver oxygen stress is one of the main extraintestinal manifestations of colitis and 5% of cases develop into a further liver injury and metabolic disease. 2′-fucosyllactose (2′-FL), a main member of human milk oligosaccharides (HMOs), has been found to exert efficient impacts on remitting colitis. However, whether 2′-FL exerts the function to alleviate colitis-induced liver injury and how 2′-FL influences the metabolism via regulating gut microbiota remain unknown. Herein, in our study, liver oxygen stress was measured by measuring liver weight and oxygen-stress-related indicators. Then, 16S full-length sequencing analysis and non-target metabolome in feces were performed to evaluate the overall responses of metabolites and intestinal bacteria after being treated with 2′-FL (400 mg/kg b.w.) in colitis mice. The results showed that, compared with the control group, the liver weight of colitis mice was significantly decreased by 18.30% (p < 0.05). After 2′-FL treatment, the liver weight was significantly increased by 12.65% compared with colitis mice (p < 0.05). Meanwhile, they exhibited higher levels of oxidation in liver tissue with decreasing total antioxidant capacity (T-AOC) (decreased by 17.15%) and glutathione (GSH) levels (dropped by 22.68%) and an increasing malondialdehyde (MDA) level (increased by 36.24%), and 2′-FL treatment could reverse those tendencies. Full-length 16S rRNA sequencing revealed that there were 39 species/genera differentially enriched in the control, dextran sulphate sodium (DSS), and DSS + 2′-FL groups. After treatment with 2′-FL, the intestinal metabolic patterns, especially glycometabolism and the lipid-metabolism-related process, in DSS mice were strikingly altered with 33 metabolites significantly down-regulated and 26 metabolites up-regulated. Further analysis found DSS induced a 40.01%, 41.12%, 43.81%, and 39.86% decline in acetic acid, propionic acid, butyric acid, and total short chain fatty acids (SCFAs) in colitis mice (all p < 0.05), respectively, while these were up-regulated to different degrees in the DSS + 2′-FL group. By co-analyzing the data of gut microbiota and metabolites, glycometabolism and lipid-metabolism-associated metabolites exhibited strong positive/negative relationships with Akkermansia_muciniphila (all p < 0.01) and Paraprevotella spp. (all p < 0.01), suggesting that the two species might play crucial roles in the process of 2′-FL alleviating colitis-induced liver oxygen stress. In conclusion, in the gut–liver–microbiotas axis, 2′-FL mediated in glucose and lipid-related metabolism and alleviated liver oxygen stress via regulating gut microbiota in the DSS-induced colitis model. The above results provide a new perspective to understand the probiotic function of 2′-FL.

• Publisher: MDPI AG,MDPI
• Subject: 2′-fucosyllactose (2′-FL) / Acetic acid / Akkermansia muciniphila / Analysis / Animals / Antioxidants / Antioxidants - metabolism / Bacteria / Butyrates - metabolism / Colitis / Colitis - chemically induced / Colitis - drug therapy / Colitis - metabolism / Colon / Colon - metabolism / Dextran Sulfate - adverse effects / Disease Models, Animal / Fatty acids / Fatty Acids, Volatile - metabolism / Food Science / Glucose - metabolism / Glutathione - metabolism / glycometabolism / gut microbiota / Humans / Inflammation / Inflammatory bowel disease / Life sciences / lipid metabolism / Liver / Liver - metabolism / liver oxygen stress / Malondialdehyde / Malondialdehyde - metabolism / Metabolism / Metabolites / Mice / Mice, Inbred C57BL / Microbiota / Microbiota (Symbiotic organisms) / Milk / Nutrition and Dietetics / Oxidative stress / Oxygen - metabolism / Paraprevotella spp / Paraprevotellaspp / Propionates / Propionates - metabolism / RNA, Ribosomal, 16S - genetics / Sciences des denrées alimentaires / Sciences du vivant / Statistical analysis / Trisaccharides