LAUSR

Purpose Human breast milk is the optimal source of nutrients for growing infants. However, many circumstances can arise which preclude breast milk feeding, leading to the use of infant formula, including during the weaning period. Many diet-related effects are modulated by the gut microbiome. Therefore, we investigated the effect of human milk (HM) or infant formula (IF) on the gut microbiota in weanling rats. Methods The gut microbiota of weanling male Sprague–Dawley rats fed HM or IF for 28 days was analysed by shotgun metagenome sequencing. Caecal contents were analysed by liquid chromatography–mass spectrometry metabolomics. Results Numerous genera within the Proteobacteria phylum were relatively more abundant in the ileum, caecum, and colon of rats fed HM, including ileal Escherichia (HM = 9.6% ± 4.3 SEM; IF = 0.9% ± 0.3 SEM; P  = 0.03). Other taxa that differed between HM- and IF-fed rats included Prevotella and Ruminococcus . Overall, more differences were observed in the ileum than the caecum and colon between rats fed HM and IF. For the rats fed IF, in the ileum, the relative abundance of Bifidobacterium was higher (HM = 1.7% ± 0.7 SEM; IF = 5.0% ± 1.5 SEM; P  = 0.04) with gene functions related to carbohydrate and amino acid metabolism also decreased. In the caecum, metabolic features such as bile acids were elevated while amino sugars were also decreased. Conclusion Our results show that HM and IF composition differences are reflected in the gut microbiome composition and function in both the small and large intestines.