Probiotic modulation of the microbiome in pregnancy and epigenetic effects on the offspring
It is now widely recognised that diet and nutrition in pregnancy are modifiable risk factors for the future metabolic health of the offspring. The ‘developmental programming of health and disease hypothesis’ has highlighted numerous environmental exposures in early life that give rise to modifications in metabolic phenotype across the life course. Epidemiological studies which demonstrate influences of maternal diet and the hormonal environment in gestation and early post-natal life on disease risk profiles, are extensively supported by animal models which have been invaluable in providing mechanistic insight and proof of principle into the phenomenon of developmental programming and its role in long-term health and disease. Linked to this phenomena and providing a potential underlying mechanism is the emerging role of the gut microbiome in linking immunity, metabolism and the transgenerational transmission of a healthy or dysmetabolic phenotype. The gut microbiota in humans contains a unique group of micro-organisms consisting of numerous bacteria and viruses which in total generate an estimated biomass of more than 1.5 kg and a combined genome or ‘microbiome’ far in excess of the human genome. These microbial genes encode some essential biological functions and are also involved in the development of innate and adaptive immunity, and recent evidence suggests that the microbiota may have key functions in regulating metabolic pathways in health and disease. We hypothesis that maternal dietary supplementation with pre- and pro-biotics in pregnancy would protect against degenerative disease which we have previously reported in the adult offspring associated with dysmetabolism in obese and diabetic pregnancy. We will test candidates from Danone’s prebiotic and probiotic research portfolio in our murine model of dysbiotic obese pregnancy and assess maternal metabolic profiles and long term metabolic outcomes in the offspring e.g. glucose homeostasis and energy balance. The influence of the maternal microbiome on the developing offspring innate immune system will be investigated together with epigenetic changes in candidate genes relating to glucose and lipid homeostasis. Epigenetics offers a molecular mechanism whereby environmental influences (e.g. diet and the microbiome) can impact on gene expression, potentially in a stable and heritable manner, to programme phenotypic traits. This collaborative research project will advance understanding of the way in which dietary nutrients and probiotics in pregnancy interact with the inherited gut micobiome to promote offspring health. This collaborative research project between King’s College London and Danone Nutricia will ultimately provide the student with a challenging research training experience, and an invaluable and unique insight into cutting edge of research and development at one the food industry’s most successful subsidiaries. The student will gain insight into both commercial and academic R&D environments and will gain from Danone Nutricia’s valuable know-how, technology and proprietary information in the field of pregnancy and infant nutrition, whilst also receiving training in state of the art in vivo physiology techniques under the auspices of a clinical academic research environment at St Thomas’ Hospital.
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