Human Milk Oligosaccharide Lacto‑N‑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-N-neotetraose (LNnT) better promotes the recovery of intestinal microbiota (chiefly Lactobacillus) and increases the level of Bifidobacterium compared to 3′-sialyllactose, 2′-fucosyllactose, and the mixture. Additionally, LNnT decreases the potential pathogenic bacteria Klebsiella level and the microbial dysbiosis index. Although supplementation with LNnT does not decrease the Clostridioides difficile burden or alleviate the decline in the fecal numbers of Lactobacillus and Bifidobacterium after C. difficile 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.