The central research goal of my lab is to improve the understanding about mechanism(s) involved in gut microbiome-mediated pathology of metabolic diseases like diabetes, obesity and aging, and to develop treatment options to prevent and/or cure these health ailments. To achieve this goal, my research program focuses on three major interconnected themes:
- Define contribution of gut microbiome/virome on microbiome-gut-brain axis to regulate energy metabolism via modulating enteroneuroendocrine-immune axis
- Development of human-origin probiotics
- Study microbiome-drug interactions to modulate drug efficacy
To accomplish the goals of our research projects, we use a combination of transgenic mice models of human disease, germ-free mice models, next generation sequencing, bioinformatics analyses in conjunction with bacteriological, biochemical, functional genomics, and ex-vivo and in-vitro models.
Microbiome-gut-brain axis in energy homeostasis
Timely communications between gut and brain are critical to regulate food intake and body metabolism; however, abnormalities causing delay in the gut-brain communication may increase risk of obesity and diabetes. Our overarching goals are to understand how gut microbiome/virome can impact the gut-brain communication through enteric neurons and endocrine cells to regulate the pathology of obesity and diabetes.
Our earlier studies showing that increased production of butyrate into the gut lumen can curve obesity and diabetes via modulating microbiome-gut hormone axis. We discovered that the butyrate increased secretion of a major gut hormone called glucagon-like protein-1 (GLP-1) to decrease obesity and diabetes via modulating hypothalamic signals of hunger-satiety mechanisms. Butyrate actions are primarily derived by free fatty acid receptor 2 and 3 (FFAR2/3) in enteric neurons and endocrine cells.
Our current studies involve deciphering how gut microbiome and its metabolites like butyrate can impact enteric neuroendocrine system to regulate food intake and food addiction behaviors via modulating gut-brain communications.
Probiosis of gut microbiome
Gut microbiome perturbations (dysbiosis) are linked with several human diseases including obesity, diabetes and aging, hence developing gut microbiome modulators such as probiotics have emerged as potential, novel and natural therapeutic options. Our research goals are to develop complex enough microbial community of human-origin probiotics (called ‘mini-microbiome’) to reverse the gut microbiome dysbiosis and benefit host metabolism to ameliorate obesity and diabetes. Our ongoing studies are testing in-house developed ‘mini-microbiome’ consortia to ameliorate diet-induced obesity and type 2 diabetes, autoimmune type 1 diabetes and aging in different research models.
Drug-microbiome interactions (Pharmacobiomics)
Variability in drug efficacy remains a serious and unresolved issue in clinical practice and the drug discovery arena, mainly because the underlying confounding factors remain largely unknown. Given that our gut microbes come in close contact with orally administered drugs, it is reasonable to hypothesize that the gut microbiome contributes to drug responsiveness versus non-responsiveness and could be a source of biomarker development to predict the drug efficacy. Our present work aims to test this central hypothesis by using metformin, currently the most commonly prescribed anti-diabetic drug, as an example.