Research Projects

Chronic liver diseases (CLD) are increasing in India due to modern lifestyles, with increased inflammatory stress and microbiota translocation driving the progression of CLD to end-stage cirrhosis. The mechanisms behind poor resolution of injury, infection, and regeneration failure are not well-defined. Stress-induced insulin resistance and bioenergy failure account for exhaustion of bone marrow (BM) hematopoietic stem cell (HSC) niche, leading to loss of HSC in cirrhosis. Gut-dysbiosis and loss of HSCs have been independently shown in cirrhosis, with loss of HSCs starting at pre-cirrhotic stages. Microbiota has been shown to regulate stressed haematopoiesis, and obesity-related gut dysbiosis has been shown to reduce HSC self-renewal, suggesting a link between gut-dysbiosis and hematopoietic dysfunction. This study aims to investigate gut-BM interaction to identify gut factors associated with loss of BM-HSCs, their role in self-renewal and differentiation of HSC, and therapeutic potential in preventing loss of HSC in-vivo. Kinetic changes in gut-microbiota, plasma metabolites, inflammatory factors, and BM haematopoiesis will be done in toxin-induced CLD mice to establish the link between gut-dysbiosis and hematopoietic dysfunction. The study will validate identified factors in cirrhotic patients with and without hematopoietic dysfunction, using data to study the therapeutic efficacy of metabolites and healthy faecal microbiota transplant in augmenting hematopoietic function in-vitro and in-vivo.