16S rRNA profiling of anal microbiota from childhood cancer survivors

Adult survivors of childhood cancers such as acute lymphoblastic leukemia (ALL) have health problems that persist or develop years after cessation of therapy. These late effects include metabolic diseases such as obesity and type-2 diabetes, but the underlying cause is poorly understood. Here, we compared the anal microbiota composition of adult survivors of childhood ALL (N=73) with healthy control subjects (N=61). We identified a dysbiotic community with reduced microbial diversity, which was associated with markers of immune dysregulation including increased T cell activation and chronic inflammation in survivors. The dysbiotic community is enriched for Actinobacteria (e.g. Corynebacterium) and depleted of Bacteroidia members and Faecalibacterium; correlating with plasma concentrations of interleukin 6 (IL6) and C-reactive protein (CRP), HLA-DR+CD4+ and HLA-DR+CD8+ T cells, which are established markers of increased inflammation and immune activation. These observations identify a link between microbial dysbiosis and increased chronic inflammation in young adult survivors of childhood ALL.