Modulation of intestinal mucosal immunity in human microbiota-associated rat by 2′-Fucosyllactose and Lacto-N-neotetraose

The objective of this study was to investigate the role of human milk oligosaccharides, specifically 2′-Fucosyllactose and Lacto-N-neotetraose, in the immunomodulation of the intestinal mucosa in human microbiota-associated rats. Evidence from studies suggests that 2′-FL and LNnT significantly alleviate damage induced by LPS in the intestines, resulting in a notable increase in DAI scores. Furthermore, 2′-FL and LNnT have been shown to enhance the function of the intestinal barrier and improve the immunity of the intestinal mucosa. This beneficial effect is achieved by increasing the mRNA expression of proteins such as MUC2, Claudin-1, Claudin-2, and ZO-1 in the intestinal tract, while simultaneously promoting a decrease in serum D-Lactate and DAO levels. 2′-FL and LNnT may also play a significant role in ameliorating intestinal immune damage. This is accomplished by suppressing the secretion of pro-inflammatory cytokines while simultaneously augmenting the production of anti-inflammatory cytokines. Furthermore, 2′-FL and LNnT are capable of modulating the cellular immune homeostasis of essential immune cells, including CD4⁺/CD8⁺, Th1/Th2, and Th17/Treg. The findings of this study also revealed that human milk oligosaccharides can ameliorate intestinal dysbiosis triggered by LPS. This includes increasing the abundance of <em>Muribaculaceae </em>and <em>Roseburia</em>, decreasing the abundance of <em>Escherichia-Shigella</em> and <em>Alloprevotella</em>. Furthermore, we conducted a more detailed investigation into the levels of major short-chain fatty acids in the feces of rats and found that 2'-FL and LNnT significantly increased the concentrations of acetate, propionate, and butyrate in the feces of LPS-treated rats. In summary, human milk oligosaccharides demonstrate a significant improvement in intestinal mucosal immunity by refining the structure of the intestinal microbiota, enhancing the functions of the intestinal barrier, and coordinating immune responses.