Human milk oligosaccharide 2'-fucosyllactose attenuates oxidative stress-induced intestinal barrier injury in mice via regulating microbial tryptophan metabolism.

The present study aimed to investigate the protective effects of 2'-fucosyllactose (2'-FL) on diquat-induced intestinal oxidative injury and the underlying involvement of the gut microbiota and microbial tryptophan metabolism in this process. Thirty-six mice were assigned to CON, diquat, and 2'-FL + diquat groups. The results indicated that the diquat injection significantly impaired the intestinal barrier, suppressed the antioxidant capacities in serum and the jejunum, downregulated the mRNA expression of genes related to redox balance, and elevated proinflammatory cytokines. All these adverse effects were alleviated by 2'-FL administration. Moreover, 2'-FL increased the abundance of Lactobacillus and the contents of indole-3-acetic acid, indole-3-acetonitrile, 3-indoleglyoxylic acid, and melatonin and activated the aryl hydrocarbon receptor (AHR) and its downstream genes, while inhibiting the expression of NF-κB and MLCK. Collectively, 2'-FL mitigated oxidative stress-induced intestinal barrier injury by promoting microbial tryptophan metabolism to activate the AHR pathway, underscoring its potential as a functional prebiotic for improving intestinal health.