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Characterization of maternal microbiota-dependent imprinting of the neonatal immune system

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Bacteria shape neonatal immune system

The first months of life are critical for immune system development and maturation. A European study looking into this process has illustrated the central role of maternal gut microbiota.

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Commensal microbiota inhabit the inner and outer body surfaces of healthy mammals, such as the skin, airways and intestine. The role of these bacteria in the intestine is well-established for the digestion of food, production of vitamins and immune protection. Changes in gut microbiota composition are associated with an increased risk of developing inflammatory bowel disease. Colonisation with beneficial bacteria starts after birth and is intricately associated with the immediate environment. This underscores the importance of exposure to the maternal microflora during early childhood in shaping the health of the infant. Scientists in the EU-funded MICROBIOTA-NEONATE (Characterization of maternal microbiota-dependent imprinting of the neonatal immune system) project set out to investigate the phenotypic and functional effects of maternal microbiota on neonatal immunity and the mechanism behind this phenomenon. The researchers exposed pregnant germ-free mice to the commensal strain of E. coli, HA107, and compared their offspring to those that had remained germ-free throughout pregnancy. They observed that offspring exposed to commensal E.coli while in the uterus had more immune cells responsible for maintaining homeostasis at the host-microbial interface as well as immunity against invading pathogens. MICROBIOTA-NEONATE scientists also demonstrated the significance of microbiota exposure during gestation. Offspring fed by germ-free mothers exhibited bacterial translocation to the lymph nodes while those exposed to maternal microbiota were protected. Furthermore, the latter expressed higher levels of genes involved in antimicrobial defence and intestinal homeostasis. Mechanistic insight indicated that the majority of the alterations observed in the offspring immune system introduced by gestational colonisation were dependent on the presence of maternal antibodies. This takes place in the uterus via the placenta and, postnatally, via the maternal milk. Interestingly, the maternal antibodies carried bacterial-derived factors in the maternal milk that could reach the offspring by gestation. Overall, the increased incidence of allergic diseases in children in developed countries, as well as neonate and child mortality from infectious diseases in developing countries, emphasise the need for improving neonatal immunity. The findings of the MICROBIOTA-NEONATE study will contribute to the prenatal prevention of allergic diseases and new therapeutic tools that reduce child mortality.

Keywords

Immune system, maternal microbiota, intestine, E.coli, uterus, gestation, antibodies, allergic disease

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