Human Milk Oligosaccharide Lacto-<i>N</i>-Neotetraose Promotes Gut Microbiota Recovery in the Context of Antibiotic-Induced Dysbiosis

Human milk oligosaccharides (HMOs) may shape intestinal homeostasis, although the optimal form of HMOs to restore the gut microbiota in antibiotic-induced dysbiosis remains unclear. Here, we found that HMOs with various structures modulate microbial communities differently after antibiotic exposure. Lacto-<i>N</i>-neotetraose (LNnT) better promotes the recovery of intestinal microbiota (chiefly <i>Lactobacillus</i>) and increases the level of <i>Bifidobacterium</i> compared to 3'-sialyllactose, 2'-fucosyllactose, and the mixture. Additionally, LNnT decreases the potential pathogenic bacteria <i>Klebsiella</i> level and the microbial dysbiosis index. Although supplementation with LNnT does not decrease the <i>Clostridioides difficile</i> burden or alleviate the decline in the fecal numbers of <i>Lactobacillus</i> and <i>Bifidobacterium</i> after <i>C. difficile</i> infection (CDI), LNnT attenuates intestinal epithelial damage, decreases inflammatory status, and alters metabolome profiles after CDI. Collectively, LNnT may function as a promising prebiotic to promote gut microbiota recovery in the context of antibiotic-induced dysbiosis.