Prenatal maternal supplementation with prebiotics regulates microbiota colonization in high-risk children, but do not prevent atopic dermatitis at one year of age
Résumé
Prenatal maternal supplementation with prebiotics regulates microbiota colonization in high-risk children, but do not prevent atopic dermatitis at one year of age. M. Bodinier1, H. Aubert2, M. Boivin3, C. Brosseau1, C. Cherbuy4, E. Dhilly5, M. Larsen5, A. Maruani6, C. Droitcourt7, J. Mazereeuw-Hautier8, E. Faurel-Paul9, A. Le Thuaut10, M. Tching-Sin11, V. Dochez12 and S. Barbarot2, 13. 1 Institut National de Recherche pour l’Agriculture, l’alimentation et l’Environnement (INRAE), UR1268 Biopolymères Interactions Assemblages (BIA), Nantes, France 2 Nantes Université, Service de dermatologie, Centre Hospitalier Universitaire de Nantes CHU Nantes, Nantes, France 3 CIC Femmes Enfants Adolescents, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France. 4 Micalis Institute, Institut National de Recherche pour l’Agriculture, l’alimentation et l’Environnement (INRAE), AgroParisTech, Université´ Paris-Saclay, Jouy-en-Josas, France 5 INSERM, CIMI, Paris, France 6 CHU de Tours, Hôpital Trousseau, Service de Dermatologie, Tours, France 7 CHU Rennes, CHR Pontchaillou, Service de Dermatologie, Rennes, France 8 CHU Toulouse, Hôpital Larrey, Service de Dermatologie, Toulouse, France 9 Direction de la Recherche, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France. 10 Direction de la Recherche, Plateforme de Méthodologie et Biostatistique, Centre Hospitalier Universitaire de Nantes, Nantes, France 11 Service de Pharmacie, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France 12 Service de Gynécologie Obstétrique, CIC Femmes Enfants Adolescents, Centre Hospitalier Universitaire de Nantes, Nantes, Pays de la Loire, France 13 Institut National de Recherche pour l’Agriculture, l’alimentation et l’Environnement (INRAE) Pays de la Loire, UMR1280 PhAN, Nantes, France Atopic Dermatitis (AD) is the most common atopic disease. AD is associated to the dysfunctions of the immune system and epithelial barriers, with an imbalance in the gut microbiota. These disorders start very early in life and some are present from birth. A primary prevention strategy for atopic diseases should therefore begin during fetal life. Nutritional intervention during pregnancy modulates the gut microbiota and implants a specific microbiota in the newborn. Prebiotics are non-digestible oligosaccharides present in food, which are able to modulate the microbiota by promoting the growth of bacteria beneficial for host health and the immune system by inducing a tolerogenic environment. Our preclinical studies highlighted that maternal prebiotic (GOS/inulin) intake reduced the risk of food allergy in the offspring. We wanted to confirm these data in AD in a clinical trial. PREGRALL (NCT03183440), a randomized placebo controlled trial, evaluated the ability of a GOS/inulin supplementation in 376 allergic pregnant women recruited in 4 French centers to prevent AD in high-risk children at 1-year-of-age (Cabridain et al., 2019). A unique biocollection of blood, stools and breast milk was generated in 126 mother-infant dyads to elucidate the mechanisms involved in AD development as well as the impact of the prebiotics in the mother and their children at 1-year-of age (CIMMAP Project). The prebiotic supplementation was not able to protect against AD at 1 year or to decrease the severity of the disease. Surprisingly, the prevalence of AD was low compared to our estimations in a population at high risk (20% instead of 45%). Interestingly, the prebiotic intake modulated the composition (of the maternal gut microbiota, particularly increasing the Bifidobacteria. Also, the rate of maternal bacteria bound to secretory IgA tend to be decreased in the prebiotic group compared to placebo. This phenotype was transmitted to the children in the first week of life. Altogether, prebiotic intake by mothers during pregnancy affects their gut microbiota and immunity and the effects are transmitted to their children in early life. The modulation of biological parameters in mother and their children by the prebiotic intervention was not able to protect against AD at one year of age but encourage us to think that the strategy could have a longer-term effect on the prevention of other atopic diseases.