The Regional Department of Clinical Microbiology, University Hospital of Region Zealand, Region Zealand, Denmark.
Department of Hematology, Zealand University Hospital, Region Zealand, Denmark.
Blood Adv. 2023 Jul 11;7(13):3326-3337. doi: 10.1182/bloodadvances.2022008555.
Chronic inflammation is believed to play an important role in the development and disease progression of polycythemia vera (PV). Because an association between gut microbiota, hematopoiesis, and inflammation is well established, we hypothesized that patients with PV have a gut microbiota distinct from healthy control participants (HCs). Recombinant interferon alfa 2 (IFN-α2)-treatment of patients with PV is reportedly 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-α2 might have a composition of the gut microbiota toward normalization. Herein, via amplicon-based next-generation sequencing of the V3 to V4 regions of the 16S ribosomal RNA gene, we report on an abnormal gut microbiota in 102 patients with PV compared with 42 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 <.001). Furthermore, we report the composition of the gut microbiota to differ between the treatment groups (IFN-α2, hydroxyurea, no treatment, and combination therapy with IFN-α2 and ruxolitinib) and the HCs. These 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.
慢性炎症被认为在真性红细胞增多症（PV）的发展和疾病进展中起重要作用。由于肠道微生物群、造血和炎症之间的关联已得到充分证实，我们假设 PV 患者的肠道微生物群与健康对照参与者（HCs）不同。据报道，重组干扰素 alfa 2（IFN-α2）治疗 PV 患者可在使升高的血细胞计数正常化方面具有疾病修饰作用，同时降低 JAK2V617F 等位基因负担。因此，我们假设接受 IFN-α2 治疗的患者可能具有正常化的肠道微生物群组成。在此，通过扩增子为基础的下一代测序 16S 核糖体 RNA 基因的 V3 至 V4 区，我们报告了 102 例 PV 患者与 42 例 HCs 相比，肠道微生物群异常。与 HCs（59%，P <.001）相比，PV 患者的 alpha 多样性较低，属于厚壁菌门（Firmicutes）的几个分类群的相对丰度较低（45%）。此外，我们报告了治疗组（IFN-α2、羟基脲、无治疗和 IFN-α2 和 ruxolitinib 的联合治疗）和 HCs 之间的肠道微生物群组成存在差异。考虑到肠道微生物群的改变对于其他疾病（包括慢性炎症性疾病）的发病机制的潜在重要性，这些观察结果非常有趣。我们的观察结果呼吁进一步进行肠道微生物群研究，以阐明治疗与 PV 和相关肿瘤中肠道微生物群之间的潜在因果关联。
