Research Description
Humanity is facing an epidemic of inter-related metabolic diseases collectively referred to as metabolic syndrome, the hallmarks of which include obesity, insulin resistance, hyperglycemia, hyperlipidemia, and hepatic steatosis. Metabolic syndrome greatly increases risk of developing diabetes, cardiovascular disease, and liver dysfunction. Modern changes in dietary habits, particularly the consumption of processed foods lacking fiber, are believed to affect gut microbiota and contribute to the increase of chronic inflammatory disease, including metabolic disease. The applicant’s recently published work supports this notion, and found that diet lacking fiber alters the composition of gut bacteria, lowering numbers overall and changing the ratios of species. Also, low-fiber diets increase bacteria's ability to encroach upon the gut's epithelial cells; this provokes an inflammatory response. Furthermore, it was found that manipulating dietary fiber content, particularly by adding fermentable fiber, guards against metabolic syndrome. However, consuming enough inulin sometimes comes with negative consequences, such as flatulence, bloating that will deter its use. For this reason, the current proposal seeks to increase understanding of mechanisms underlie diet-induced obesity and offer deeper insight into fermentable fibers might promote better health, will explore new strategies to target gut or gut microbiota that will avoid adverse effect but yet treat and/or prevent metabolic disease.Research Profile
What area of diabetes research does your project cover? What role will this particular project play in preventing, treating and/or curing diabetes?While diet has long been presumed an important factor in driving the disease of diabetes, recent studies show an important role for gut microbiota in mediating the influence of diet on metabolic health. My recent study supported this notion in that it demonstrated that decreased consumption of soluble fiber increase proneness to dysglycemia. Moreover, this work showed that one key means by which fiber protects against dysglycemia is by inducing the cytokine IL-22. The studies proposed in my ADA award focus on the understanding how soluble fiber elevates IL-22 level in intestine to restore host-microbiota homeostasis, and defining the mechanism by which IL-22 influence glycemic control. The major goal of the proposed studies is to investigate the interaction mechanisms among dietary fiber, gut microbiota and host metabolic disease, which may be exploited to provide new approaches by targeting gut microbiota or IL-22 to therapeutic interventions for metabolic disease.
If a person with diabetes were to ask you how your project will help them in the future, how would you respond?My work shows that signals from bacteria that normally reside in the intestine, which scientists refer to as the “gut microbiota”, play an important role in maintain health metabolism. My work aims to understand how the microbiota impacts health, in particular how it influences intestinal health and how it can promote development of diabetes. Briefly, the intestine is not merely a vehicle to absorb ingested nutrients but rather is an important metabolic organ, which plays a key role in the pathophysiology of metabolic syndrome. The intestine is normally colonized by a large diverse collection of microorganisms, including 100 trillion bacteria comprised of several thousand species, collectively called the gut microbiota, aids a wide range of intestinal functions. The soluble fiber such as inulin, resists digestion in the small intestine but is readily fermented by bacteria in the colon. Our project aims to investigate the interaction among dietary fiber, gut microbiota, intestinal function and glycaemia control. Knowing detailed mechanisms by which dietary fiber regulate gut microbiota to benefit host to control glucose will bring gut microbiota targeted therapies to prevent or cure diabetes.
Why important for you, personally, to become involved in diabetes research? What role will this award play?My overall long-term career goal is to become a successful productive independent academic researcher whose work advances public health. While the research investigating how gut microbiota affect host metabolic function can serve as vehicle to help me achieve this goal, funding from ADA would be tremendously helpful as it will provide me the support to establish my lab and research program while I continue to build the skills I need for a successful career in academic medical research.
In what direction do you see the future of diabetes research going?I believe that gut-targeted therapy will be one important way to treat diabetes in future. Understanding the interaction mechanism between gut microbiota and intestinal function may have promise to adjusting gut microbiota to alter intestinal function (including the secretion of hormones involved in the regulation of appetite) to prevent and treat diabetes.