The human gut microbiota is a complex ecosystem consisting of hundreds to thousands of distinct bacterial species which provide important immune, metabolic and trophic functions for their host. Our knowledge on the processes contributing to microbial dysbiosis has a direct impact on our ability to manage and maintain human health. Early childhood appears a crucial age-window since diversification and maturation of the microbiota primarily occurs during this period under the influence of host development and dietary changes. Early life dietary exposures may dominate over factors such as host genetics in modifying the type and distribution of gut organisms and contribute to disturbances in the gut microbiome, leading to impairment in allergen tolerance, abnormal fat accretion, chronic obesity and metabolic derangement. Previous research has linked weaning and the introduction to solid foods to the transition of an infant to adult microbiota, however, longitudinal studies directly linking cessation of breast-milk or timing of introduction of solid foods with the composition of the microbiome or associations with obesity or allergy were largely lacking. Our project aimed to identify the impact of early life dietary events among infants born at term and preterm on gut microbiome community structures and the subsequent association with health outcomes.
To address this aim we prospectively collected data from ~1000 newborns in Canada, the Netherlands and Germany with multiple biological sampling points to enable longitudinal characterization of microbial communities using 16S rRNA gene profiling of all faecal samples and metagenomic and metabolomic studies on a subset of infants.
Thus far we have found that during the first year of life the development of the microbiome is characterised by an increasing diversity and a shift from a high abundance in bifidobacteria and facultative anaerobes towards butyrate-producing genera within the order of Clostrida. Birth mode was a major driver of microbiota community structure in the first month of life, while thereafter diet became the strongest driving force of microbiota composition. Our Intensively Sampled Sub-Study demonstrated that the introduction of solid foods has an impact on the developing infant gut microbiome and that nutritional choices influence the changes that occur. Overall, this study contributes new knowledge to the research topic of the development of the gut microbiota in infancy and the influences of early dietary choices.

- In a longitudinal study of fecal microbiota among children with a genetic predisposition for atopy, from 5 weeks through 6 to 11 years, we tracked changes in gut microbial diversity and composition that were associated with the development of atopic dermatitis, allergic sensitization, and asthma. Members of the Lachnospiraceae family, as well as the genera Faecalibacterium and Dialister, were associated with a reduced risk of atopy.

- Capitalizing on a policy change, we compared preterms given probiotic supplements as part of routine care to those who received none. Our study showed that probiotic bacteria given to preterm infants while they are hospitalized may still be present in their stool for many weeks after supplementation was stopped. Infants that were administered the probiotic had a gut microbial community that was more like healthy 10-day-old full-term infants, suggesting that the probiotic is helping to promote better gut colonization overall.

- Microbiome development throughout the first year of life is characterised by an increasing diversity and a shift from a high abundance in, amongst others, bifidobacteria and facultative anaerobes towards butyrate-producing genera within the order of Clostrida (e.g. Faecalibacterium and Blautia) (all cohorts).

- Despite similar trends in microbiota maturation and harmonisation of all steps from metagenomic DNA isolation to bioinformatic analyses, the microbiota composition significantly differed between cohorts from different geographic regions (all cohorts).

- Birth mode appeared to be a major driver of microbiota community structure in the first month of life, while thereafter diet became the strongest driving force of microbiota composition (PAPS, LucKi). Cessation of breastfeeding had a more pronounced impact on the microbiota maturation than the introduction of solid foods (Lucki, PAPS).

- The introduction of solid foods has an impact on the developing infant gut microbiome and nutritional choices influence the changes that occur, but the jurisdictional cohort that the participant belonged to and differences in individual characteristics were stronger predictors of variation in the gut microbiota (Intensively Sampled Sub-Study; Baby & Mi, LucKi). During the introduction of solid foods, higher fiber intake and high dietary diversity were associated with higher microbial alpha diversity. High daily dietary diversity was associated with stability of the gut microbiota over the study period.