Human Milk Microbiota composition and function
Abstract
Although human milk (HM) has long been considered sterile, microorganisms have emerged as a natural part of this nutritional fluid even in healthy women. Based on the growing literature on HM microbiota, this presentation will provide an overview of this microbial community, its composition and influencing factors, and then focus on the role of this HM microbial component in infant gut homeostasis based on our recent findings.
The HM microbiota is characterised by a low microbial load but a high diversity with several dozen genera and more than 200 species identified so far1. The fungal and viral milk communities have also begun to be studied. Several factors contribute to shaping the milk microbiota or affect its composition, including host and environmental factors, as well as methodological factors that are likely to introduce bias in milk microbiota analysis. The origin of the HM microbiota remains controversial. HM microbiota is likely to be a combination of microorganisms from the mother's skin and infant's oral cavity, as well as from the mother's gut via an as yet hypothetical entero-mammary pathway.
Recent evidence on its role in infant physiology and health suggests that the HM microbiota contributes to infant gut homeostasis. The milk microbiota is not only a reservoir of beneficial bacteria for the infant gut microbiota, but more globally contributes to its shaping2. To better understand the role of the HM microbiota as a complex microbial community on intestinal homeostasis, including immune and barrier functions, we recently used a disassembly/reassembly strategy combined with in vitro and in vivo approaches3. A collection of HM bacteria was established from 28 healthy, exclusively breast-feeding mothers. HM strains covering the diversity of cultivable HM microbiota were first characterised individually and then assembled into synthetic bacterial communities (SynComs) of 11 strains using two human cell models, peripheral blood mononuclear cells and a quadricellular model mimicking intestinal epithelium. Selected HM bacteria displayed a wide range of immunomodulatory properties and had variable effects on the epithelial barrier, with no clear association with taxonomy. More importantly, the assembly of HM strains into two SynComs of similar taxonomic composition, but with strains exhibiting different individual properties, resulted in contrasting effects on the epithelium. The effects of these SynComs were further evaluated in vivo: three groups of 2-day-old Yucatan mini-piglets (n=10 per group) were either fed a formula without supplementation or supplemented at a physiological dose with a SynCom with an anti-inflammatory (AI) or high immunomodulatory (HI) profile and compared with a group of sow milk-fed piglets. Daily supplementation with these two SynComs differentially modulated gut microbiota composition beyond the presence of SynCom bacteria in the gut and altered gut physiology, in particular intestinal immune and barrier signatures. Changes in physiological variables were directly correlated with the presence of SynCom bacteria, particularly in the ileum, or indirectly through their effects on the microbiota, as in colon.
In conclusion, HM microbiota, as a complex and variable microbial component, likely contribute to the development of intestinal homeostasis in infant. The functional profile of bacteria forming the human milk microbiota may induce a different developmental profile of infant gut physiology. Further exploration of the relationships between HM microbiota composition and infant intestinal homeostasis and health should help us to unravel the complex relationships between breastfeeding and infant health, opening new avenues for the development of strategies aimed at controlling infant gut homeostasis for health benefits.
1.Oikonomou, G. et al. Milk microbiota: what are we exactly talking about? Front. Microbiol. 11, (2020).
2.Boudry, G. et al. The Relationship Between Breast Milk Components and the Infant Gut Microbiota. Front. Nutr. 8, 629740 (2021).
3.Le Bras, C. et al. Two human milk-like synthetic bacterial communities displayed contrasted impacts on barrier and immune responses in an intestinal quadricellular model. ISME Commun. ycad019 (2024) doi:10.1093/ismeco/ycad019.