Does intermittent fasting during pregnancy alter the intestinal microbiome of the offspring?

Although exempt, many pregnant Muslim women take part in the daily fast during the month of Ramadan. The long term effects on the child are not fully known, although an association between exposure to fasting in utero and an increased incidence of mental impairment has been shown.

Recent advances in the understanding of the gut-brain axis and its potential association with the microbiome suggest that the gut microbiota may influence brain development. The metabolic capability of the residing gut microbiota may contribute to brain function. Bacterial fermentation of host fibre results in the production of short chain fatty acids (SCFA) such as butyrate. The exact role of bacterial metabolites in brain development is unclear: butyrate has been shown to ameliorate behavioural changes induced by phencyclidine yet it has also been linked to the development of autism.

We have developed a rat model of intermittent fasting during pregnancy, to mimic aspects of Ramadan fasting. Maternal fasting results in the development of smaller fetuses with reduced head circumference. The impaired growth of the brain appears to affect cognitive function and social behaviour. In preliminary studies we have shown that male, but interestingly not female, offspring displayed significant differences in the relative abundance of the Bacteroidetes and Firmicutes phyla in their gut profiles.

The aim of this project is to determine the impact of intermittent fasting during pregnancy on the gut microbiota of rat offspring and its potential influence on cognitive development. Metagenomics employing MiSeq analysis will be used to determine the composition of the gut microbiota through the 16S rRNA gene. Compositional differences in census data will be determined using R and used to assess impact on cognitive development and function.

This project interfaces with our current ongoing studies investigating how maternal intermittent fasting during pregnancy influences offspring metabolism, physiology and function.

Training/techniques to be provided:

This project will employ in silico, in vivo and in vitro techniques. Bioinformatics training will focus on the handling and processing of deep sequencing data. MiSeq analysis will be used in conjunction with Linux based open access software packages and R for statistical analyses. The study will employ a rat model and will involve animal handling, breeding and the manipulation of both maternal and offspring diets. Behavioural studies will include tests of several cognitive domains such as working memory and attention; social processes and positive valence systems such as approach motivation and affective bias; and anxiety related behaviours. Full training will be provided and the candidate will be expected to pass a Home Office personal licensee training course. Training will be provided in a range of microbiological analyses, molecular and biochemical techniques, including qPCR, immunoblotting, immunohistochemistry, immunofluorescence, enzyme activity and transporter assays.