Life Sciences & Biotechnology
Title : | Exploration of the role of gut microbiome dysbiosis in post-transplant diarrhea and its clinical impact on host immunity and graft outcomes in kidney and bone marrow transplant recipients |
Area of research : | Life Sciences & Biotechnology |
Focus area : | Microbiome Research |
Principal Investigator : | Dr. Sapna Pahil, Post Graduate Institute Of Medical Education And Research (PGIMER), Chandigarh |
Timeline Start Year : | 2024 |
Timeline End Year : | 2027 |
Contact info : | sapnapahil@gmail.com |
Details
Executive Summary : | Transplant patients develop infections easily due to prolonged immunosuppressive drug usage and diarrhoea is the most common complaint in patients after bone marrow transplantation (BMT) and kidney transplantation. Despite being the frequent complaint in posttransplant recipients, the etiology of diarrhoea in transplant recipients remains elusive or poorly defined. Numerous factors contribute to post transplant survival and graft function, making it a challenging task in both kidney transplant and allogeneic hematopoietic stem cell transplant (allo-HSCT). Recently, disturbances in gut microbiota (GM) have been associated with a number of adverse post-transplant complications in BMT and kidney transplant recipients. The gut microbiome is a vast community of microorganisms inhabiting the gastrointestinal (GI) tract which is highly host specific and evolves throughout an individual’s lifespan. Prolong use of antibiotics and the preparative immunosuppressive regimen such as mycophenolate mofetil (MMF) prior to transplantation causes depletion of normal gut flora, resulting in gut-dysbiosis. Gut Microbiota is not only involved in protection against various diseases but also regulates numerous metabolic pathways, gut and immune homeostasis. It plays an important role in the developing functional innate and adaptive immunity. Gut bacteria are also involved in modulating host’s immune pathways as they secrete various immunomodulatory agents. Gut microbiota also controls the host’s innate and adaptive immune response to bacterial antigens, autoantigens, and allo-antigens and dysbiosis of gut imbalances this regulation thereby impacting autoimmunity, allo-immunity and graft survival. Gut dysbiosis is recently being identified to play a major role in posttransplant outcomes and there are very few studies available on this issue. As recent research revealed the association of gut dysbiosis with inflammation and the changes in immune homeostasis has adverse effects on graft survival but data is very less and research on this subject is still in nascent phase. Exploration of role of microbiota in kidney and bone marrow transplantation seems promising to enhance our understanding of the microbiota-host interactions, effect on immune responses and to develop new therapeutic strategies for the management of patients and allograft outcomes. In the proposed study, we will try to explore the possible changes in gut microbiota in posttransplant diarrhoea patients, try to test all possible GI pathogens by multiplex PCR and finally study the effects of gut dysbiosis on alteration of host immune homeostasis by studying various cytokines and long-term effects on graft functions. The GM and the host's immune system’s bidirectional interactions need to be explored for better outcomes in organ transplantation and immuno-suppression. |
Co-PI: | Dr. Ashish Sharma, Post Graduate Institute Of Medical Education And Research (PGIMER), Chandigarh-160012, Dr. Neelam Taneja, Post Graduate Institute Of Medical Education And Research (PGIMER), Chandigarh-160012, Dr. Alka Rani Khadwal, Post Graduate Institute Of Medical Education And Research (PGIMER), Chandigarh-160012, Dr. Balvinder Mohan, Post Graduate Institute Of Medical Education And Research (PGIMER), Chandigarh-160012 |
Total Budget (INR): | 53,73,764 |
Organizations involved