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.