Understanding role of diet on microbiome injury and patient outcome for hospitalized Allo-HCT patients

Nutrition is a key determinant of microbiome composition, but this relationship is poorly understood in humans under perturbations such as antibiotics, intestinal inflammation, anorexia, or hospitalization. There exists profound intestinal-microbiota disruption that accompanies hematopoietic cell transplantation (HCT) and its related treatments, including antibiotics and chemotherapy. Using paired nutrition data and sequenced stool samples from 173 hospitalized HCT patients we have uncovered a link between increased sucrose intake and a reduction in microbiota ɑ-diversity in patients receiving antibiotic treatment. Furthermore we observed these patients have an increased likelihood of Enterococcus domination events, an observation we previously reported as a predictor of mortality in this population. We have experimentally recapitulated this antibiotic-induced Enterococcus domination and loss of diversity in mice, and are exploring the metagenomic and metatranscriptomic profiles of the cecal-microbiome before and after injury. Initial data suggest that the antibiotic treatment appears to drive the early transcriptional response regardless of dietary intervention, however a distinct sucrose-dependent transcriptomic profile emerges on day 3 after antibiotic exposure. This suggests that diet, and thus nutritional intervention, may play a role in determining community recovery following disruption by antibiotics. Further explorations can help us identify specific mechanisms and suggest strategies for promoting healthy microbiota recovery after dysbiotic incidents and improving clinical outcomes following hematopoietic cell transplantation.