The Impact of Human Milk Oligosaccharides on Antibiotic-Induced Microbial Dysbiosis and Gut Inflammation in Mice.

Background/Objectives: Antibiotics have a significant impact on the gut microbiota, and we hypothesized that human milk oligosaccharides may alleviate antibiotic-induced gut microbiota dysbiosis. Methods: Six groups of eight mice were administered drinking water with or without ampicillin for one week. We then introduced the human milk oligosaccharide 2'-fucosyllactose (2'FL), either alone or in combination with difucosyl-lactose (DFL), for two weeks after the termination of ampicillin treatment. Results: Ampicillin reduced microbiota diversity and the abundance of specific bacteria. One week after the termination of ampicillin treatment, the 2'FL + DFL mixture counteracted the ampicillin-induced reduction in diversity, although this effect was not sustained. Over the subsequent two weeks, the 2'FL + DFL mixture had a significant impact on the relative abundances of Lactobacillus spp. and Bacteroides spp. Ampicillin also reduced caecal propionate levels, downregulated the gene Gzmb for Granzyme B, and upregulated the gene Reg3a for Regenerating islet-derived protein 3 alpha, all of which were counteracted by the 2'FL + DFL mixture. Ampicillin had a minor impact on ileal cytokine levels. The 2'FL + DFL mixture showed a cytokine effect indicating reduced adaptive and innate inflammation. Ampicillin reduced water intake and growth in the mice. The oligosaccharides did not affect water intake, but the 2'FL + DFL mixture slightly reduced body weight. Conclusions: The 2'FL + DFL mixture appears to hold potential for counteracting some of the side effects of ampicillin treatment.