From infancy to childhood: the intersection of gastrointestinal microbial communities, diet and health
Background and aim
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.
Our work has begun to generate new information on several topics within the infant gut microbiome field of research. Our findings show that there is an association between specific gut microbial communities and subsequent development of atopy; we have also described patterns of colonization during critical life transitions including the early weeks of life after preterm birth; the impact of probiotics on the preterm gut; and during the introduction of solid foods among full term healthy infants in two different jurisdictions and among preterm infants. This work contributes to the understanding of how the gut is colonized in early life, factors that may be associated with short- and long-term microbial changes and how this may impact future clinical outcomes. Future research may utilize the factors that we have found to be associated with gut microbial patterns and clinical outcomes in order to develop a primary prevention tool, such as diet modification as therapy. Our team plans to continue this important work and will seek funding in order to further analyse the rich datasets that we have created.
|Charité Medical University
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.
Author: J Penders* and N van Best
Author: CM Homann, CAJ Rossel, S Dizzell, L Bervoets, J Simioni, J Li, E Gunn, MG Surette*, RJ de Souza, M Mommers*, EK Hutton*, KM Morrison*, J Penders*, N van Best and JC Stearns*
Author: S Dizzell, JC Stearns*, J Li, N van Best, L Bervoets, M Mommers*, K Morrison*, EK Hutton*, J Penders*, on behalf of the GI-MDH Consortium Partners*
Author: G Galazzo, N van Best, L Bervoets, IO Dapaah, PH Savelkoul, MW Hornef, GI-MDH Consortium*, S Lau*, E Hamelmann*, J Penders*
Author: EI Yousuf, M Carvalho, SE Dizzell, S Kim, E Gunn, J Twiss, L Giglia, C Stuart, E Hutton*, the Baby & Mi Study Group, KM Morrison*, JC Stearns*
Author: Renz H, Adkins BD, Bartfeld S, Blumberg RS, Farber DL, Garssen J, Ghazal P, Hackam DJ, Marsland BJ, McCoy KD, Penders J*, Prinz I, Verhasselt V, von Mutius E, Weiser JN, Wesemann DR, Hornef MW
We have formed cohorts of ~1000 full and pre-term infants and collected data on perinatal and early infancy exposures as well as detailed longitudinal data, and for some infants, frequent faecal sampling during periods of great dietary change (introduction of solid foods and weaning from breastmilk). Together, our cohorts contribute greatly to the understanding of how nutritional practices in infancy influence health in the longer term via the gut microbiome.
Over the course of the first year of life we have found that 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 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. Cessation of breastfeeding had a more pronounced impact on the microbiota maturation than the introduction of solid foods.
Frequent faecal sampling and dietary data collection in our Intensively Sampled Sub-Study revealed that the introduction of solids induces gradual changes in the infant gut microbiome, rather than rapid and stark differences. To our knowledge, this study was the first to collect detailed dietary data on a day-to-day basis during an important dietary milestone in infancy followed by evaluation of the gut microbiome to 12–14 months of age. The gut microbiome of infants at the time of solid foods showed high inter-individual variability. There were also strong jurisdictional cohort effects, which was expected, as the composition of the gut microbiome is known to vary by geographical area. Despite these differences by cohort and individual, we found that dietary diversity was positively associated with stability of the microbial community in both Canadian and Dutch infants suggesting that a diverse diet stabilizes the composition of the gut microbiota during solid food introduction. Bifidobacterial taxa were positively associated, while taxa of the genus Veillonella, that may be the same species, were negatively associated with dietary diversity in both cohorts. These findings indicate that dietary diversity is beneficial to a healthy gut microbiome, as bifidobacteria have many beneficial effects on the human host.
In the preterm population we have used a change in clinical practice to observe changes in the gut microbiome after administration of a probiotic supplement. 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.
We have also identified specific microbial communities that appear to be associated with atopic disease in children and after further research this information may lead to interventions to treat or prevent atopy.