From infancy to childhood: the intersection of gastrointestinal microbial communities, diet and health
|Partner Organization||Partner Country|
|Charité Medical University||Germany|
|Maastricht University||The Netherlands|
1. Overall project description
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. Cessation of breastfeeding had a more pronounced impact on the microbiota maturation than the introduction of solid foods. We are currently working on describing the changes that occur in the infant gut microbiome during the introduction of solid foods and the factors that appear to drive changes in diversity and composition.
- 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).
4.1 List of publications
|Authors||Title||Year, Issue, PP||Doi|
|G Galazzo, N van Best, L Bervoets, IO Dapaah, PH Savelkoul, MW Hornef, GI-MDH Consortium, S Lau, E Hamelmann, J Penders||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||2020 May;158(6):1584-1596||10.1053/j.gastro.2020.01.024|
|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||The neonatal window of opportunity-early priming for life||2018 Apr;141(4):1212-1214||10.1016/j.jaci.2017.11.019|
4.2 Presentation of the project
|Target group||Authors||Means of communication||Hyperlink|
|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||Download|
|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||Download|
|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||Download|
|Scientists, students||K Morrison. Inaugural DOHaD@MAC Research Day, Hamilton, Canada, 2016||Invited oral presentation|
|Academia||J Penders. “Establishment of the microbiome in early infancy”. The neonatal window of opportunity, early priming for life congress, Hanover, Germany, 2016.||Invited oral presentation||Link|
|Academia and (Food & Pharma) Industry||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||Download|
|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||Download|
|Academia||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. “From Infancy to Childhood: GastroIntestinal Microbial Communities, Diet, and Health.” JPI Symposium, 2017.||Oral presentation||Download|
|Academia||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||Download|
|Academia||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||Download|
|Academia||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||Download|
|Academia||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||Download|
|Academia||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||Download|
|Scientists||J Penders. “From Infancy to Childhood: GastroIntestinal Microbial Communities, Diet, and Health.” JPI Symposium, 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.” 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|
|Academia||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||Download|
|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|
|clinicians and researchers within all aspects of allergology||J. Penders. “Establishment of the infant microbiome” Nordic Allergy Symposium, 2018. Audience: clinicians and researchers within all aspects of allergology||Invited oral presentation||Link|
4.3 List of submitted patents and other outputs
|Patent licence||Partners involved||Year||International eu or national patent||Comment|