Abstact

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Today, one third of children worldwide are either undernourished or overweight. Early life under- and over-nutrition (jointly termed malnutrition) are increasingly recognized as key risk factors for adult obesity and metabolic syndrome, which affect 1.9 billion adults globally.

In this proposal, we hypothesize that the early life microbiota plays a crucial role in this double burden of malnutrition, and that properly timed microbiota-targeted interventions can breach the vicious trajectory from early life malnutrition to metabolic disease.  Humans are colonized at birth with an initial set of bacteria (“seed microbiota”), which, under the influence of different environmental exposures, gradually evolve into the complex microbiota seen in adults. In vaginally born infants, this seed microbiota is coming mainly from the mother’s fecal, vaginal and oral microbiota.

To date, little is known regarding the contribution of the maternal microbiota to children’s early life microbiota and on the early epigenetic imprinting increasing the risk of metabolic disease in later life.  This projects aims to close this knowledge gap by addressing the following questions:

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• Are there differences in the oral and vaginal microbiota of under- or over-nourished mothers ?

• What is the effect of maternal vaginal and oral microbiota on the developing fecal microbiota of infants ?

• What is the effect of the maternal vaginal and oral as well as the infant’s oral microbiota on the infant’s nutritional status, metabolic health and epigenetic imprinting ?

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Capitalizing on an ongoing birth-cohort in Lao People’s Democratic Republic (Lao PDR) (VITERBI GUT project, see study protocol in Tamarelle, Crézé et al, Journal of Nutrition 20231), we will follow 300 mother-infants dyads for two years after birth, analyzing their microbiota using 16S amplicon sequencing/shotgun metagenomics, metabolic parameters, and the blood epigenetic profile. The main objective of VITERBI GUT is the role of mothers and infants fecal microbiota on epigenetic imprinting and metabolic health. Expanding VITERBI GUT, the proposed project will analyze two important alternative seeding sources for infant’s early life microbiome: the maternal oral and vaginal microbiota.  

The proposed project aims at generating new evidence on mother-infant microbiota transmission and will be the first to analyze possible shared microbial signatures and mechanisms linking early life over- and undernutrition to metabolic disease in later life. This work will set the stage for developing powerful microbiota-targeted intervention strategies to promote healthy childhood development.

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