Food DNA Sequencing Reveals Associations between Dietary Perturbations and Patient Outcomes in Hematopoietic Stem Cell Transplant

Malnutrition affects 80% of cancer patients and is a well-documented prognostic factor for survival. However, assessing dietary patterns has been challenging as dietary recall surveys are limited by memory and literacy. To overcome these limitations, we leveraged a novel food DNA sequencing pipeline, FoodSeq, which amplifies and sequences plant and animal DNA markers derived from residual food materials found in stool samples. This permits retroactive examination of patients’ diets at various timepoints pre- and post-transplant. We applied FoodSeq to stool samples collected from 162 patients with hematologic malignancies who underwent hematopoietic stem cell transplantation (HCT) from 2015 to 2021.FoodSeq illuminated multiple unique clinical findings from the stool samples of our cohort. Principal component analysis (PCA) on abundances of food taxa showed significant changes in patients' diet across HCT timeline (PERMANOVA p = 0.001) (Figure 1). The first principal component (PC1) captures overall consumption of common foods, whereas the second (PC2) moderately reflect food preferences. This highlights that patients experienced a dietary perturbation during transplant.We next evaluate how patients' dietary quality changed during HCT. We evaluated patients’ diet using plant and animal metabarcoding diversity (referred to as pMR and aMR respectively) across HCT timeline and observed a significant reduction of plant dietary diversity (pMR) within the first 4 weeks post-transplant (Figure 2). Also, we found a significant reduction of animal dietary diversity (aMR) within the first 3 weeks post-transplant, but not on week 4 (p=0.067).To evaluate how diet correlates to engraftment outcomes, we compared by transplant type and conditioning regimen intensity using the same PC1 and pMR data sets in stool samples collected in the first two-weeks post-transplant. Taxonomic abundance (PC1) was negatively correlated with faster platelet recovery (the first of three consecutive days with platelet count greater than 20 × 10^9/L without transfusion support) in allogenic HCT patients who received myeloablative conditioning (AlloMA) (p<0.024) (Figure 3). This suggests that increased dietary abundance correlated with quicker platelet recovery. The relationship was not significant in allogenic HCT patients who received reduced intensity or nonmyeloablative conditioning or autologous HCT patients. The relationship also was not significant between PC1 and neutrophil recovery in all transplant-conditioning groups.These dietary perturbation and platelet recovery results highlight the need for further research to evaluate how various conditioning regimens and transplant types differentially impact the patient's diet. Our research also highlights the importance of diet during cancer treatment and highlight a need for better and standardized dietary surveillance during HCT.