Bovine colostrum supplementation rescues early-life antibiotic-induced dysbiosis and reduces long-term obesity risk

The prevalence of metabolic disease in the United States has increased from 30.4% to 41.9% since 2013 with 17.2% of children affected. Evidence implicates intestinal microbiome dysbiosis with metabolic disease risk, and while antibiotics can be lifesaving, they cause ecological instability in the microbiome. Colostrum is the first milk produced by mammals immediately after birth, and its primary function is to provide the nutrition and bioactive compounds to support gastrointestinal tract immune system develop. Considering the impact of colostrum in the sterile-like early-life gut, we hypothesized that bovine colostrum provided as a supplement would augment gut microbial recolonization and improve intestinal cell function following antibiotic exposures and mitigate long-term metabolic consequences. To test this hypothesis, specific pathogen-free (SPF) C57BL/6 mice (n = 18 three-week old males, Jackson Laboratory) were housed under standard laboratory conditions with a 45% high-fat diet. The animals were divided into three groups: control, antibiotics (ABX), and antibiotics followed by colostrum (ABX + Colostrum). Tylosin tartrate, a veterinary form of azithromycin, was administered to the ABX and ABX + Colostrum groups in drinking water 3 days per week over three weeks, with 4 days washout periods. The ABX + Colostrum group received bovine colostrum immediately following antibiotic exposures via oral gavage. The experiment repeated 3 times, differing only in experiment endpoint to analyze samples during, immediately following, or 16 weeks after intervention. The primary outcomes were body composition, lipid metabolism, glucose homeostasis, fecal microbiota community composition, and gene expression in the jejunal transcriptome. Systemically, the ABX + Colostrum group exhibited reduced long-term fat gain and improved glucose metabolism. Specific to the digestive tract, ABX + Colostrum group had an increased fecal relative abundance of Akkermansia and Parasutterella during and after the bovine colostrum pulse. These genera were correlated to elevated fat mass gain and dysregulated glucose metabolism. The ABX + Colostrum demonstrated significant upregulation of Defa20 and Spdef, demonstrating potential stimulation of Paneth cell function and a downregulation of genes responsible for lipid absorption and repackaging. Taken together, these data suggest colostrum may stimulate epithelial responses that foster host-microbial symbiosis at the mucosal surface and play a beneficial role in intestinal recolonization to improve metabolic homeostasis locally and systemically after antibiotic exposure. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.