Exploring the Effects of Dietary Interventions on Gut Microbiota Dynamics in Obesity and its Health Implications in C57Bl/6 Male Mice

Abstract

Gut microbiota is increasingly recognized as a promising target for therapeutic interventions aimed at preventing and managing obesity and associated dysfunctions. Recently, there has been a growing interest in the consumption of functional foods, like dietary pulses with a unique nutrient-dense profile, linked to enhanced intestinal health by interacting closely with the gut microbiota, weight management, cognitive function, and significant improvement in overall health. This thesis explored the intricate interplay of diet, gut microbiota, and metabolic health in the context of obesity through three linked projects. In Project 1, the impact of incorporating white and dark red kidney beans into a low-fat diet (LFD) was explored, focusing on fecal gut microbiota composition and function, inflammatory state, and metabolic health in high-fat diet (HFD)-induced obese male mice. Project 2 broadened the scope to explore the influence of common beans on the gut-brain axis. This included an assessment of cecal microbiota, colon histomorphology, and anxiety behaviors and well-being. The findings from these two projects highlighted that, compared to the HFD fed obese control group, transitioning to an LFD supplemented with beans led to reduced weight gain, enhanced body composition (increased FFM and decreased FM), caused distinctive fecal and cecal microbiota changes at both phyla and genus levels with notable shifts in the abundance of specific beneficial bacterial genera, particularly those associated with short-chain fatty acids (SCFAs) production. While both bean varieties enhanced the gut microbiota microenvironment, they revealed unique effects on certain bacterial taxa, attributed to their distinct phenolic contents. On the other hand, beans did not promote additional improvements in fasting serum metabolic outcomes, beyond those induced from transitioning to an LFD, except for reduced inflammatory adipokine resistin by dark beans. The study found no improvements in nest-building behavior, indicative of well-being, but did observe some evidence of anxiolytic effects in the Elevated Plus Maze (EPM) test, particularly with white bean supplementation. Project 3 explored the intricate interplay among diet, inflammation, and gut microbiota in the development of obesity phenotypes. This project elucidated the potential contributions of Akkermansia genus abundance in generating phenotypes resistance to obesity and associated inflammatory and metabolic dysfunctions, even under an HFD with ad libitum food access. Overall, the findings of this thesis contribute to our understanding of factors contributing to diet-induced obesity phenotypes and emphasize the potential health implications of specific bean varieties, providing insights into both physiological and mental health outcomes in C57Bl/6 male mice models.