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

Med Microbiol Immunol. 2020 Dec;209(6):693-703. doi: 10.1007/s00430-020-00694-y. Epub 2020 Sep 29.

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.

MeSH terms

  • Adult
  • Aged
  • Antigens, CD / blood
  • Antigens, Differentiation, Myelomonocytic / blood
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Bacterial Translocation*
  • Bacteriophages / isolation & purification*
  • C-Reactive Protein / analysis
  • Female
  • Gastrointestinal Microbiome*
  • Humans
  • Intestinal Mucosa / drug effects*
  • Intestinal Mucosa / microbiology
  • Leukemia, Myeloid, Acute / blood*
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / microbiology
  • Leukemia, Myeloid, Acute / virology
  • Lipopolysaccharide Receptors / blood
  • Macrophage Activation
  • Male
  • Middle Aged
  • Permeability
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / blood
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / microbiology
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / virology
  • RNA, Bacterial / blood*
  • RNA, Ribosomal, 16S / blood*
  • Receptors, Cell Surface / blood
  • Viremia / diagnosis*
  • Viremia / etiology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antineoplastic Agents
  • CD14 protein, human
  • CD163 antigen
  • Lipopolysaccharide Receptors
  • RNA, Bacterial
  • RNA, Ribosomal, 16S
  • Receptors, Cell Surface
  • C-Reactive Protein