Jenny Paredes, PhD, on How Increased Fiber Intake Results in Better Overall Survival and Lower GI-aGVHD in Allo-HCT Recipients and Pre-Clinical GVHD Models

My study addressed the question of can we use dietary fiber to iterate the outcomes of Allo HCT patients? We did this study at Memorial Sloan Kettering Cancer Center, where we follow 173 patients. We recorded their daily intake of all the nutrition factors that they had, including parental nutrition, drinks, food, snacks, everything. It was a very tailored study, and with this information, we were able to calculate the grams of fiber that they ate every single day before transplantation and after transplantation. So our data covers 10 days before transplantation all the way to 30 days post transplantation. The most interesting result that we saw is definitely the fact that we saw an increase in overall survival in these patients. We saw a difference, a consistent gap of 10% in our landmark analysis covered all the way to 24 months. So we're very excited about these findings. In addition to this, we address GVHD risk, and for this purpose, we focus on lower GI GVHD patients, which is one of the most severe versions of GVHD. And our main findings are an increase in acute GVHD cumulative incidence in all the patients, and we saw a lower incidence in lower GI GVHD patients. So again, very exciting findings that we hope that we can continue to record more data and do other multi-center validations. In addition, we use a preclinical model of GVHD. So these are mouse models because we wanted to address what are the potential mechanisms that fiber can contribute to changes in the microbiome and GVHD risk. So for this purpose, I chose cellulose, which is the most abundant fiber in nature. And in addition to this, since mammals don't have the sematic machinery to break it down, we solely rely on the microbiome. So all our results were very confident that our microbiome dependent in this model, we saw the rich fiber diet, which is 12%, resulted in an increased survival to GVHD. We saw through single cell sequencing that the main contributions are mediated by epithelial hemostasis, as well as a downregulation of T-cell mediated by CD4 T cells. So taking all this together, we would like to invite clinicians and institutions to first take into consideration these results to perhaps rethink the menus that are offered for bone marrow transplantation at institutions and think of strategies to increase fiber intake. But we acknowledge that this is a challenging task, especially for patients that develop IBD like symptoms. But we would like to invite the community to approach personalized medicine case to case basis to increase fiber intake. Some of our take home messages is that when we saw a difference in 10 grams of fiber intake per day between the low fiber intake and high fiber intake groups, we saw a benefit in terms of microbiome diversity production or short-chain fatty acids that we have known for a while are beneficial for epithelial hemostasis. So that's the invitation that we would like to stand, and we're looking forward to publish these results and to continue with our project.