Breastfeeding and the major fermentation metabolite lactate determine occurrence of in infant feces.

Previous studies indicated an intrinsic relationship between infant diet, intestinal microbiota composition and fermentation activity with a strong focus on the role of breastfeeding on microbiota composition. Yet, microbially formed short-chain fatty acids acetate, propionate and butyrate and other fermentation metabolites such as lactate not only act as substrate for bacterial cross-feeding and as mediators in microbe-host interactions but also confer antimicrobial activity, which has received considerably less attention in the past research. It was the aim of this study to investigate the nutritional-microbial interactions that contribute to the development of infant gut microbiota with a focus on human milk oligosaccharide (HMO) fermentation. Infant fecal microbiota composition, fermentation metabolites and milk composition were analyzed from 69 mother-infant pairs of the Swiss birth cohort Childhood AlleRgy nutrition and Environment (CARE) at three time points depending on breastfeeding status defined at the age of 4 months, using quantitative microbiota profiling, HPLC-RI and H-NMR. We conducted fermentations in the presence of HMO fermentation metabolites and determined the antimicrobial activity of lactate and acetate against major and representatives. Our data show that fucosyllactose represented 90% of the HMOs present in breast milk at 1- and 3-months post-partum with fecal accumulation of fucose, 1,2-propanediol and lactate indicating fermentation of HMOs that is likely driven by . Concurrently, there was a significantly lower absolute abundance of in feces of exclusively breastfed infants at 3 months. , lactate inhibited strains of . Taken together, this study not only identified breastfeeding dependent fecal microbiota and metabolite profiles but suggests that HMO-derived fermentation metabolites might exert an inhibitory effect against selected gut microbes.