The Gut Microbiota in Patients with Polycythemia Vera is Distinct from that of Healthy Controls and Varies by Treatment

Abstract

Chronic inflammation is believed to play an important role in the development and disease progression of polycythemia vera (PV). Since an association between gut microbiota, hematopoiesis, and inflammation is well established we hypothesized that patients with PV have a gut microbiota distinct from healthy controls. Recombinant interferon-α2 (IFN) treatment of patients with PV has been shown to be disease-modifying in terms of normalization of elevated blood cell counts in concert with a reduction in the JAK2V617F allelic burden. Therefore, we hypothesized that patients treated with IFN might have a composition of the gut microbiota towards normalization. Herein, via amplicon-based next generation sequencing of the V3-V4 regions of the 16S rRNA gene, we report on an abnormal gut microbiota in 102 patients with PV as compared with 42 healthy controls (HCs). Patients with PV had a lower alpha diversity and a lower relative abundance of several taxa belonging to Firmicutes (45%) compared with HCs (59%, p<0.001). Furthermore, we report the composition of the gut microbiota to differ between the treatment groups (IFN, hydroxyurea, no treatment, combination therapy with IFN and ruxolitinib) and the HCs. The observations are highly interesting considering the potential pathogenetic importance of an altered gut microbiota for development of other diseases, including chronic inflammatory diseases. Our observations call for further gut microbiota studies to decipher potential causal associations between treatment and the gut microbiota in PV and related neoplasms.