Long-term impact of gestational and early-life dietary habits on infant gut immunity and disease risk
Man is colonized immediately upon birth by environmental microbes of primarily maternal origin. Initial colonization and transfer of maternal immunity through breastfeeding are believed to impact infant health at short- and long-term by conferring protection from infection and potentially resistance to metabolic and allergic diseases.
Our objectives are to assess the importance of dietary habits on neonatal colonization and gut immunity. To attain these goals, we will analyze meconium samples from formula- versus breastfed children. Our analysis includes microbiome composition, secretory-IgA immune-microbiome and (xeno)-metabolomics. In vitro studies will define the impact of selected metabolites on gut microbiota composition and validate by comparison with ex vivo data linking metabolites and microbiota composition. Finally, integrative exposome analysis will combine experimental and epidemiological data to provide associations with life style and clinical outcome.
Presently, partner UPMC has provided access to meconium samples from 60 children stratified for allergic outcome and breastfeeding (EDEN cohort). Partner UPMC has equally recruited 600 mother-child couples (EXHES), for which we have obtained 230 meconium samples. The meconium samples have been processed by partner CIMI to extract microbes (metagenomic and immune-metagenomic analysis) and fecal water (metabolomics analysis). Ex vivo analysis of the fraction of microbes bound by immunoglobulins have been effectuated The microbiota composition and Immuno-microbiome analysis of this cohort is in progress by partner CIMI. Partner TNO has conducted extensive metabolomics analysis of fecal water samples. Partner URV has acquired 20 paired breastmilk and meconium samples and CNR has obtained 27 longitudinal meconium samples from twins. The URV samples have been analyzed for xenometabolites, which will be used to validate a Physiologically based pharmacokinetic (PBPK) model describing transfer of xenometabolites from mother to child through breastfeeding. The samples from URV and CNR have been send to Paris (Partners CIMI and UPMC). Aliquotes and shipment of samples to other partners is in progress (temporarily halted by the COVID-19 epidemics).
The program will identify predictive biomarkers and early-life preventive strategies for the growing epidemic of human metabolic and allergic diseases. Such advances may have important impact on public health and generate socio-economic benefits.
|IPLESP INSERM UPMC
|Department for Microbiology and Systems Biology (TNO)
|TecnATox, Universitat Rovira i Virgili (URV), Tarragona
|Pulmonary Environmental Epidemiology Unit (EPAP), CNR Institute of Clinical Physiology, Pisa (Italy) (CNR)
The EarlyFOOD consortium has recruited approximately 300 mother-child couples for whom we have infant fecal samples at birth (n=301) and at 1-2 years of age (n=66). We equally have maternal fecal samples (n=49). These fecal samples will be analysed for microbial composition and anti-microbial immunity as well as metabolite content. Associated with dietary and epidemiological data we expect to identify dietary influences on key biological and clinical parameters, which could pave the way for new mechanistic studies and guide political decision making.
Author: Remy VILLETTE, Gaelle AUTAA, Sophie HIND, Johanna B HOLM, Alicia MORENO-SABATER and Martin LARSEN*