Synbiotic Modulation of the Microbiome in Pregnancy and Epigenetic Effects on the Offspring

Strategic Research Priority: World Class Underpinning Bioscience

Obesity, which is defined as an "abnormal or excess fat accumulation that may impair health" is now considered a global epidemic, aptly termed - 'Globesity'. In 2014, 600 million adults over the age of 18 were classified as obese, and between 2011 and 2014, 41 - 44 million children (7%) under the age of 5 were considered to be obese or overweight according to the World Health Organisation. The aetiology of obesity is multifactorial, and is caused by an array of environmental, genetic and physiological factors which can occur during life, and according to current literature, even earlier in gestational development. Dr Paul Taylors' group at Kings College London has developed a pregnant rodent model of diet-induced obesity, where following obesogenic diet ingestion, the animals express an obese phenotype, and this obese phenotype is "programmed" into the offspring when compared with non-obese controls. The human gut microbiota - the microbial ecosystem living within the human gut, has recently been identified as another environmental mechanism which has the ability to epigenetically alter host homeostasis provoking disease. Many studies have shown that the microbiota is heavily modulated by nutrients and diet consumed by the host, leading us to speculate about the microbiota potential contributions to this developmental programming of obesity observed in the maternal diet-induced obesity offspring. Therefore, the aim of this project is to work in collaboration with industrial partner, Danone Nutricia, and attempt to modulate the microbiota using synbiotics (combinations of pre and probiotics) during obese pregnancy, to prevent the deleterious programming of obesity in the offspring. We will determine the effect of the microbiota on developmental programming of offspring obesity using synbiotic supplementation - a combination of prebiotics fructooligosaccharide and galactooligosaccharide, and probiotic Bifidobacterium m16v (m16v) - to determine the role the microbiota has in provoking or potentiating the obese phenotypes observed in our model.

Firstly, we must determine viability of probiotic cells in the delivery vehicle. This has been tested with m16v in drinking water and in jelly-based formats, both of which has been unsuccessful. In drinking water m16v was shown to degrade 99.8% in 24 hours, potentially due to osmotic lysis and the anaerobic nature of the probiotic, while m16v was unsuccessfully cultured in the jelly, potentially due to lysis or the presence of m16v toxic products in the jelly. Our next step is to trial probiotic viability in a "Nutella" pellet, a vehicle which has been shown to be palatable, and may have minor implications on probiotic counts, which will be confirmed on culture.

Secondly from probiotic validation, the aim of the first experiment will be to supplement obese dams during the pre- and postnatal periods and observe metabolic outcomes of the offspring, compared to non-supplemented groups. The aim of the second experiment which will follow will be to supplement obese dams during the pre- and postnatal periods and observe the metabolic changes of those dams in those pre and postnatal periods, to correlate distinct windows off effect on developmental programming of the offspring. During both experiments the primary samples of collection will be stool and urine, where analysing these samples at set time points, using metabonomics, metataxonomics and metagenomics; we can determine what microbial species are there, what are they doing and what metabolites are the host/bacteria producing, which could be causing/preventing the programming of offspring obesity.