Investigating the Impact of Diet, Exercise and Early-Life Adversity on the Intestinal Epithelium

Sail, Shruti Santosh (2025) Investigating the Impact of Diet, Exercise and Early-Life Adversity on the Intestinal Epithelium. Masters thesis, Indian Institute of Science Education and Research Kolkata.

Text (MS Dissertation of Shruti Santosh Sail (20MS204)) 20MS204_Thesis_file.pdf - Submitted Version Restricted to Repository staff only Download (35MB)

Abstract

The Intestinal Epithelium is a dynamic barrier vulnerable to various forms of stress, the dysfunction of which is implicated in a host of different conditions such as IBS, Metabolic Syndrome, Diabetes, Colorectal cancer etc. This thesis aims to study the impact of dietary stress and exerciseinduced stress by establishing adult zebrafish models and the impact of early life adversity on modulating the gut epithelium in a pre-established rat model of maternal separation. I first established a solid starch overfeeding in mTOR heterozygous adult zebrafish to address whether mTOR happloinsufficiency has an impact on the carbohydrate metabolism and gut architecture of zebrafish. We found that there was significant weight gain among all groups over the course of the paradigm, and no signficant difference in the fasting blood glucose between the groups at the end of the experiment. I also established an exercise model in adult zebrafish to address whether exercise on its own under normocaloric conditions has an impact on the gut architecture. I found that the average weight and blood glucose of exercised animals seems to go down, but these trends were not replicated in the second cohort for this paradigm. Tissue has been fixed for both these cohorts and further histopathological and immunological analysis will provide more information on the tissue- and organ- level impact of both these paradigms. The second part of my project focuses on the impact of maternal separation on the intestinal epithelium in rats. Particularly, I investigated whether there is an involvement of the gut-brain axis in the pathogenesis of accelerated ageing in maternally separated rats, and does Nicotinamide alleviate these effects via modulating the gut barrier? Histological analysis of the gut tissue from the three regions of the small intestine (the Duodenum, Jejunum and the Ileum) revealed that there was no difference in the gut architecture between the controls and maternally separated animals, whereas nicotinamide treatment tended to increase the villus width of all three regions and decrease the villus height especially in the Ileum in both the controls and maternally separated animals.

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