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).