GI-MDH

From infancy to childhood: the intersection of gastrointestinal microbial communities, diet and health

Project description

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.

Expected impact

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.

Consortium

Partner Organization Partner Country
Charité Medical University Germany
Maastricht University The Netherlands

Highlights

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.

Products

Title: Book Chapter in - Evolution, Biodiversity and Reassessment of the Hygiene Hypothesis - Editors Graham Rook and Chris Lowry. Chapter 6 - The development of the gut microbiota in childhood and its distortion by lifestyle changes (in press).
Author: J Penders* and N van Best
Title: Infants’ First Solid Foods: Impact on Gut Microbiota Development in Two Intercontinental Cohorts
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*
Link: https://doi.org/10.3390/nu13082639
Title: Investigating colonization patterns of the infant gut microbiome during the introduction of solid food and weaning from breastmilk: A cohort study protocol
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*
Link: https://doi.org/10.1371/journal.pone.0248924
Title: Development of the Microbiota and Associations with Birth Mode, Diet, and Atopic Disorders in a Longitudinal Analysis of Stool Samples, Collected From Infancy Through Early Childhood
Author: G Galazzo, N van Best, L Bervoets, IO Dapaah, PH Savelkoul, MW Hornef, GI-MDH Consortium*, S Lau*, E Hamelmann*, J Penders*
Link: https://doi.org/10.1053/j.gastro.2020.01.024
Title: Persistence of suspected probiotic organisms in preterm infant gut microbiota weeks after probiotic supplementation in the NICU
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*
Link: https://doi.org/10.3389/fmicb.2020.574137
Title: The neonatal window of opportunity-early priming for life
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
Link: https://doi.org/10.1016/j.jaci.2017.11.019

Reports


Endreport

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.

Target group Authors Means of communication Hyperlink Pdf
Health care providers E Hutton,* J Stearns.* “The microbiome: a new frontier”, Association of Ontario Midwives Research Symposium, Hamilton, Canada, 2017 Keynote address    
Health care providers E Hutton.* “The Baby and Mi Project: progress to date”, Hamilton Area Midwives Rounds, Hamilton, Canada, 2017 Oral presentation    
Health Care Providers J. Penders,* L Bervoets. “The LucKi Gut Study: goals and design”. Presented at: - Midwives Round South Limburg area, Netherlands 2017 - Gynaecoligists Maastricht University Medical Center+, Netherlands 2017 - Gynaecologists Zyderland Hospital Heerlen, Netherlands 2017 Oral presentation    
Scientists J Stearns,* K Morrison,* A Holloway,* M Surette,* L Thabane,* H McDonald,* A Mousseau, J Schertzer,* E Ratcliffe,* J Simioni, E Gunn, E Hutton.* “The development of the gut microbiome after exposure to Intrapartum antibiotics (IPA):The Baby &Mi prospective cohort Study”, Canadian National Perinatal Research Meeting 2016, Banff, Canada, 2016 Poster presentation    
Scientists K Morrison,* E Hutton,* H McDonald,* A Holloway,* J Schertzer,* M Surette,* L Thabane*, A Mousseau, J Stearns*, J Simioni, E Gunn “The Baby & Microbiota of the Intestine Project”, Innovation Fund Showcase 2016, Toronto, Canada, 2016 Poster presentation    
Scientists K Morrison.* Inaugural DOHaD@MAC Research Day, Hamilton, Canada, 2016 Invited oral presentation    
Scientists J Penders.* “Establishment of the microbiome in early infancy”. The neonatal window of opportunity, early priming for life congress, Hanover, Germany, 2016. Audience: Academia Invited oral presentation LINK  
Scientists J Penders.* “Establishing a causal link between gut microbes and body weight – towards the identification of key players”. Beneficial Microbes Conference, Amsterdam, the Netherlands, 2016 Invited oral presentation LINK  
Scientists K Morrison,* A Holloway*, J Stearns,* M Surette,* H McDonald,* E Ratcliffe,* J Schertzer,* L Thabane,* J Simioni, E Gunn, E Hutton* “The Baby & Microbiota of the Intestine Cohort Studies: Baby & Mi and Baby & PreMi,” 6th Annual In-FLAME Workshop, New York, USA, 2017 Oral presentation    
Scientists N van Best, P. Savelkoul, L. Bervoets, M. Hornef, M. Mommers*, J Penders*. “Impact of breastmilk and solid food on human gut microbial colonization: the LucKi birth cohort”. 6th Annual In-FLAME Workshop, New York, USA, 2017 Oral presentation LINK  
Scientists N van Best, P Savelkoul, . Schaap, S Olde-Damink, J Penders,* M Hornef. “Postnatal development of the murine gut microbiota.” 6th Annual In-FLAME Workshop, New York, USA, 2017 Oral presentation LINK  
Scientists E Hutton,* K Morrison,* A Holloway,* J Stearns,* M Surette,* H McDonald,* E Ratcliffe,* J Schertzer,* L Thabane,* M Mommers,* L Bervoets, N van Best, S Lau*, E Hamelmann,* J Penders* “From Infancy to Childhood: The Intersection of Gastrointestinal Microbial Communities, Diet and Health,” 6th Annual In-FLAME Workshop, New York, USA, 2017 Oral presentation    
Scientists J Penders,* L Bervoets, Bervoets L, Massa G, Guedens W, Louis E, Noben JP, Adriaensens P. “Metabolic profiling of the type 1 diabetes mellitis in children by proton NMR-based metabolomics.” 6th Annual In-FLAME Workshop, New York, USA, 2017 Oral presentation LINK  
Scientists J Penders.* The early life microbiome in health and disease”. The Finish Gut Day, Helsinki, Finland, 2017. Invited oral presentation    
Clinicians and scientists J Penders.* “Microbiome development from cradle to grave”. Dutch Society of Gastroenterology Spring Meeting, Veldhoven, the Netherlands, 2017. Invited oral presentation    
Scientists J Penders.* “From Infancy to Childhood: GastroIntestinal Microbial Communities, Diet, and Health.” JPI Symposium, 2017. Oral presentation    
Scientists E Yousuf, E Gunn, V Vaughan Williams, M Carvalho, J Simioni, J Twiss, L Giglia, A Holloway,* H McDonald,* E Ratcliffe*, J Schertzer,* M Surette,* J Stearns,* L Thabane*, C Stuart, G Travis, E Hutton*, and K Morrison.* “Establishing the Relationship Between Gut Microbiota and Early-Life Lean Mass in Preterm Infants.” Presented at: - EMPhasis on Health Research Symposium, Hamilton, Canada, 2017 - McMaster Child Health Research Day, Hamilton, Canada, 2017 Poster presentation    
Scientists L ElDakiky, S Dizzell, J Simioni , E Gunn, K Morrison,* E Hutton,* M Surette,* J Stearns.* “Impact of solid food introduction on microbial succession in the infant gut.” Presented at: - McMaster Medical Sciences Research Day. Hamilton, Canada, 2017 - 6th Annual EMPhasis on Health Research Symposium, Hamilton, Canada, 2017 - Michael DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day, Hamilton, Canada, 2017 Poster presentation    
Scientists E Yousuf, M Carvalho, S Dizzell, E Gunn, J Simioni, J Twiss, E Hutton*, K Morrison,* J Stearns*. “Exploring the viability of early gut microbiota analysis in preterm infants” McMaster Child Health Research Day, Hamilton, Canada, 2018 Oral presentation    
Scientists E Yousuf, M Carvalho, S Dizzell, E Gunn, J Simioni, J Twiss, E Hutton*, K Morrison,* J Stearns*. “Exploring the viability of early gut microbiota analysis in preterm infants” Presented at: Pediatric Academic Society Conference, Toronto, Canada, 2018. Poster presentation    
Scientists B Singh, S Dizzell, L ElDakiky, E Hutton,* K Morrison,* J Stearns*. “Analytical methods for relatively low diversity microbial communities such as the infant gut microbiome - the case of the missing bfidobacteria.” Presented at: - Michael DeGroote Institute for Infectious Disease Research (IIDR) Trainee Day, Hamilton, Canada, 2019 - 2019 McMaster FHS Plenary, Hamilton, Canada, 2019 Poster presentation    
Scientists C Homann, S Dizzell, J Li, E Gunn, R de Souza, E Hutton*, J Stearns*, K Morrison*. “Dietary Intake and the Gut Microbiome in Full-Term Infants at Introduction of Solid Foods: A Longitudinal Study.” Presented at: - Child Health Research Day, Hamilton, Canada, 2019 - MODR Research Blitz, Hamilton, Canada, 2019 - Canadian National Perinatal Research Meeting, Banff, Canada, 2020 - Medical Sciences Research Day, McMaster University, Hamilton, Canada, 2020 Poster presentation    
Scientists E Yousuf, M Carvalho, S Dizzell, E Gunn, J Simioni, J Twiss, E Hutton*, K Morrison*, J Stearns*. “Exploring the early development of the preterm gut microbiome”. Canadian National Perinatal Research Meeting, Montebello, Canada, 2019. Poster presentation    
Scientists J Penders*. “From Infancy to Childhood: GastroIntestinal Microbial Communities, Diet, and Health.” JPI Symposium, 2019. Oral presentation LINK  
  G Galazzo, J Penders.* “An altered gut microbiota establishment in early life is linked with the development of atopic dermatitis.” Dutch Society for Medical Microbiology Annual Spring Meeting, 2019. Oral presentation LINK  
Scientists G Galazzo, J Penders*. “An altered gut microbiota establishment in early life is linked with the development of atopic dermatitis.” World of Microbiome: Pregnancy, Birth & Infancy Conference, Milan, Italy, 2019. Poster presentation LINK  
Scientists E Yousuf, M Carvalho, S Dizzell, E Gunn, J Simioni, J Twiss, E Hutton*, K Morrison*, J Stearns*. “Persistence of bacteria in the preterm infant gut week after probiotic supplementation in the NICU.” Canadian National Perinatal Research Meeting, Banff, Canada, 2020. Poster presentation    
Scientists and clinicians J Penders*. “Update on gut microbiota and allergic diseases.” Allergie im Fokus-Veranstaltung der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI), 2020. Invited oral presentation LINK  
Physicians, dietitians, pharmacists, nutritionists, scientists and nurses involved in the field of nutrition and metabolism J Penders. “Population-based metagenomics analysis” European Society for Clinical Nutrition and Metabolism Annual Congress (ESPEN), 2017. Invited oral presentation    
Clinicians and researchers within all aspects of allergology J Penders*. “Establishment of the infant microbiome” Nordic Allergy Symposium, 2018. Invited oral presentation LINK  
Scientists and clinicians EI Yousuf, N Rochow, J Li, J Simioni, E Gunn, EK Hutton*, and KM Morrison*. Growth and Body Composition Trajectories from 6 Weeks to 5 Months in Healthy, Breast-Fed, Term-Born Infants. UBC's 8th Conference on Recent Advances in the Prevention & Treatment of Childhood and Adolescent Obesity (Virtual). October 2020. Poster presentation    
Scientists and clinicians N van Best and J Penders*. “On the origin of species - Establishment of the microbiome and its role in allergy development”. European Allergy and Clinical Immunology Congress. Krakow, Poland, July 2021. Invited oral presentation    

Subjects

Features

Project number:
GI-MDH
Duration: 100%
Duration: 100 %
2016
2020
Related subsidy round:
Project lead and secretary:
Eileen K Hutton