Summary

The greatest influence on the development and establishment of the gut microbiota occurs at birth when the infant is exposed to vaginal, fecal, and skin microbiota from the mother and to microbes from the environment. The early intestinal colonization of functional microbial groups plays an essential role in infant gut health, with most studies targeting the initial colonization period from birth to 6 months of age. Although the composition and diversity of the infant gut microbiota has been well described at a taxonomic level, functional aspects of this ecosystem remain little explored. This presentation will attempt to summarize many years of research carried out in collaboration with the Division of Gastroenterology and Nutrition and the Nutrition Research Unit of the University Children‘s Hospital Zurich on functional characterization of the healthy infant gut microbiome during the first 2 years of life.

Using a combination of culture dependent, molecular and metabolic profiling methods, we first showed that some species of bacteria supplied in the human milk play an important role in the establishment of a balanced trophic chain in the neonatal gut, which may prevent disorders associated with the accumulation of intestinal lactate. Next, we characterized the evolutive colonization of functional groups and identified keystone species involved in lactate cross-feeding in healthy infants. The interactions of such species and their main metabolic products (acetate, propionate and butyrate) could have direct impacts on infant health, either beneficial (production of short chain fatty acids) or detrimental (accumulation of hydrogen or hydrogen sulfide).

Dysregulation of the metabolism of lactate has been suggested as one of many causes in the etiology of gastrointestinal symptoms, such as infant colic, a functional gastrointestinal disorder that affects up to 20% of infants. In a cohort of healthy infant, we detected specific functional signatures between colicky and non-colicky infants and for crying and non-crying infants, associated with cross-feeding of both lactate and hydrogen, supporting that an imbalance towards increased H2 production could be a contributing factor to IC. As a result, BactoKindTM is currently developed as a first synergistic bacterial formulation with mechanistic basis to prevent and treat IC.

Our findings present the early establishment of the infant gut microbiome with a novel functional perspective and emphasize the importance of lactate utilization in infancy.