JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms

Author:

Eickhardt‐Dalbøge Christina Schjellerup123ORCID,Nielsen Henrik V.3ORCID,Fuursted Kurt3ORCID,Stensvold Christen Rune3ORCID,Andersen Lee O' Brien3,Lilje Berit3,Larsen Morten Kranker24ORCID,Kjær Lasse2ORCID,Christensen Sarah Friis2ORCID,Knudsen Trine Alma2ORCID,Skov Vibe2ORCID,Sørensen Anders Lindholm2ORCID,Ellervik Christina456ORCID,Olsen Lars Rønn7ORCID,Christensen Jens Jørgen Elmer18ORCID,Nielsen Xiaohui Chen1ORCID,Hasselbalch Hans Carl24ORCID,Ingham Anna Cäcilia3ORCID

Affiliation:

1. The Regional Department of Clinical Microbiology University Hospital of Region Zealand Slagelse Denmark

2. Department of Hematology Zealand University Hospital Roskilde Denmark

3. Department of Bacteria, Parasites & Fungi Statens Serum Institut Copenhagen Denmark

4. Faculty of Health and Medical Sciences University of Copenhagen Copenhagen Denmark

5. Department of Pathology Harvard Medical School Boston Massachusetts USA

6. Department of Data and Data Support Region Zealand Sorø Denmark

7. Department of Health Technology Technical University of Denmark Lyngby Denmark

8. Institute of Clinical Medicine University of Copenhagen Copenhagen Denmark

Abstract

AbstractBackgroundEssential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are myeloproliferative neoplasms (MPN). Inflammation is involved in the initiation, progression, and symptomology of the diseases. The gut microbiota impacts the immune system, infection control, and steady‐state hematopoiesis.MethodsWe analyzed the gut microbiota of 227 MPN patients and healthy controls (HCs) using next‐generation sequencing. We expanded our previous results in PV and ET patients with additional PV, pre‐MF, and MF patients which allowed us to compare MPN patients collectively, MPN sub‐diagnoses, and MPN mutations (separately and combined) vs. HCs (N = 42) and compare within MPN sub‐diagnoses and MPN mutation.ResultsMPN patients had a higher observed richness (median, 245 [range, 49–659]) compared with HCs (191.5 [range, 111–300; p = .003]) and a lower relative abundance of taxa within the Firmicutes phylum; for example, Faecalibacterium (6% vs. 14%, p < .001). The microbiota of CALR‐positive patients (N = 30) resembled that of HCs more than that of patients with JAK2V617F (N = 177). In JAK2V617F‐positive patients, only minor differences in the gut microbiota were observed between MPN sub‐diagnoses, illustrating the importance of this mutation.ConclusionThe gut microbiota in MPN patients differs from HCs and is driven by JAK2V617F, whereas the gut microbiota in CALR patients resembles HCs more.

Funder

Statens Serum Institut

Kræftens Bekæmpelse

Publisher

Wiley

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