Elevated plasma phage load as a marker for intestinal permeability in leukemic patients

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ORIGINAL INVESTIGATION

Elevated plasma phage load as a marker for intestinal permeability in leukemic patients Xue‑rui Yin1 · Ping Liu1,2 · Xi Xu1 · Ying Xia1 · Kai‑zhao Huang1 · Qiong‑dan Wang1,3 · Mei‑mei Lai1 · Qi‑gui Yu4 · Xiao‑qun Zheng1,5  Received: 16 February 2020 / Accepted: 18 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020

Abstract Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman’s rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients. Keywords  Acute leukemia · Gut phages translocation · Monocyte/macrophage activation · qPCR

Introduction Edited by Christian Bogdan. Electronic supplementary material  The online version of this article (https​://doi.org/10.1007/s0043​0-020-00694​-y) contains supplementary material, which is available to authorized users. * Xiao‑qun Zheng [email protected] 1



The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

2



Qilu Children’s Hospital of Shandong University, Jinan 250000, China

3

The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, China

4

Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA

5

School of Laboratory Medicine and Life Sciences, The Key Laboratory of Laboratory Medicine, Ministry of Education of China, Wenzhou Medical University, University Town, Room 327, Tongren Building, Chashan, Wenzhou 325000, Zhejiang, China



The gut is a huge microbial habitat, hosting a variety of microorganisms including bacteria, archaea, viruses, and eukaryotic microorganisms, and is also an active immunological site [1–3]. There have been massive achievements of how human-associated bacterial communities interact with our immune system and how they affect our health [2–4]. However, it was not known until the last few years that bacteriophages (phages), bacterial viruses, could also influence im