Interactions and functionalities of the gut revealed by computational approaches

The gastrointestinal tract is subject of much research for its role in an organism’s health owing to its role as gatekeeper. The tissue acts as a barrier to keep out harmful substances like pathogens and toxins while absorbing nutrients that arise from the digestion of dietary components in in the lumen. There is a large population of microbiota that plays an important role in the functioning of the gut. All these sub-systems of the gastrointestinal tract contribute to the normal functioning of the gut. Due to its various functionalities, the gut is able to respond to different types of stimuli and bring the system back to homeostasis after perturbations.

The work done in this thesis uses several bioinformatic tools to improve our understanding of the functioning of the gut. This was achieved with data from model animals, mice and pigs which were subjected to changing environments before their gastrointestinal response was measured. Different types of stimuli were studied (eg, antibiotic exposure, changing diets and infection with pathogens) in order to understand the response of the gut to varying environments. This data was analysed using different data integration techniques that provide a holistic view of the gut response.

Vertical data integration techniques look for associations between different types of ~omics data to highlight possible interactions between the measured variables. Lateral integration techniques allow the study of one type of ~omics data over several time points or several experimental conditions. Using these techniques, we show proof of interactions between different sub-systems of the gut and the functional plasticity of the gut. Of the several hypotheses generated in this thesis we have validated several using existing literature and one using an in-vitro system. Further validation of these hypotheses will increase understanding of the responses of the gut and the interactions involved.