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

ABSTRACT

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 ¹H-NMR. We conducted in vitro fermentations in the presence of HMO fermentation metabolites and determined the antimicrobial activity of lactate and acetate against major Clostridiaceae and Peptostreptococcaceae 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 Bifidobacterium. Concurrently, there was a significantly lower absolute abundance of Peptostreptococcaceae in feces of exclusively breastfed infants at 3 months. In vitro, lactate inhibited strains of Peptostreptococcaceae. 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.

GRAPHICAL ABSTRACT

KEYWORDS:

• Exclusively breastfeeding
• gut microbiota
• lactate
• Peptostreptococcaceae
• HMO fermentation metabolites

Disclosure statement

No potential conflict of interest was reported by the author(s).

Data availability statement

The authors confirm that the data supporting the findings of this study are either submitted to public repository (PRJNA616703) or available within the article and its supplementary materials.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2241209

Additional information

Funding

CS acknowledges funding from the Aarhus Universitets Forskningsfond (starting grant to CS) and the Novo Nordisk Foundation (NNF21OC0066725). Furthermore, the study was funded by the Christine Kühne-Center for Allergy Research and Education (CK CARE).