Microbiome among Survivors
We next analyzed features of the microbiome among survivors based on previous exposures that we hypothesized to cause long-term changes in the microbiome. Alpha diversity differed between the type of disease survivors experienced (hematologic malignancies, central nervous system tumors, other solid tumors, or bone marrow transplantation for a non-malignant condition), but smaller group sizes limited ability to make definitive comparisons (Supplementary Figure 1). We did not observe a correlation between the time from diagnosis to study enrollment and the Shannon index (R=0.04, p=0.80).
To measure overall chemotherapy intensity, cyclophosphamide equivalent dosing was calculated for each survivor [30]. We did not observe a correlation between cyclophosphamide equivalent dose and Shannon index (R=0.03, p=0.89). In contrast, we did detect several differently abundant taxa between those who received above and below the mean cyclophosphamide equivalent dose (Supplementary Figure 2a).
We next determined the role of antibiotic intensity on the microbiome in survivors by calculating the total days of intravenous broad spectrum antibiotics received during the treatment period. We did not observe a correlation between total days of broad spectrum antibiotics and Shannon index (R=0.06, p=0.81). However, we did observe several differently abundant taxa between those who received above and below the mean antibiotic days (Supplementary Figure 2b).
We also examined the role of radiation therapy on the microbiome in the survivor cohort. Survivors who had radiation exposure to the abdomen or pelvis were compared to those survivors who did not receive radiation to these locations. For those that received radiation to the abdomen/pelvis, α-diversity as measured by Shannon and Simpson indices was reduced compared to those that did not (p<0.05 for both)(Figure 4a). Further, differently abundant taxa were seen between these two groups, with those having received radiation to the abdomen/pelvis demonstrating a greater proportion of severalBifidobacterium ASVs whereas those that did not receive radiation had a greater abundance of several Blautia ASVs (Figure 4c). We also analyzed the impact of radiation exposure to the central nervous system and found that those that received central nervous system radiation had decreased α-diversity as measured by Shannon and Simpson index (Figure 4b).