Lung microbiome in children with hematological malignancies and lower respiratory tract infections

Abstract

Background: Respiratory infectious complications remain a major cause of morbidity and mortality in children with hematological malignancies. Knowledge regarding the lung microbiome in aforementioned children is limited.

Methods: A prospective cohort was conducted, enrolling 16 children with hematological malignancies complicated with moderate-to-severe lower respiratory tract infections (LRTIs) versus 21 LRTI children with age, gender, weight, and infection severity matched, with no underlying malignancies, to evaluate the lung microbiome from bronchoalveolar lavage fluid samples in different groups.

Results: The lung microbiome from children with hematological malignancies and LRTIs showed obviously decreased α and β diversity; increased microbial function in infectious disease:bacteria/parasite; drug resistance:antimicrobial and human pathogenesis than the control group; a significantly reduced proportion of Firmicutes, Bacteroidota, Actinobacteriota; increased Proteobacteria at the phylum level; and distinctly elevated Parabacteroides, Klebsiella, Grimontia, Escherichia_Shigella, unclassified_Enterobacteriaceae at the genus level than the control group. Furthermore, it was revealed that α diversity (Shannon), β diversity (Bray-Curtis dissimilarity), Proteobacteria at the phylum level, and unclassified_Enterobacteriaceae and Escherichia_Shigella at the genus level were significantly negatively associated with hospitalization course whereas Firmicutes at the phylum level was established positively correlated with the hospitalization course.

Conclusions: Children with hematological malignancies and LRTIs showed obviously decreased α and β diversity, significantly increased function in infectious disease pathogenesis, antimicrobial drug resistance, and unfavorable environment tolerance. Moreover, α diversity (Shannon), β diversity (Bray-Curtis dissimilarity), and Proteobacteria may be used as negative correlated predictors for hospitalization course in these children whereas Firmicutes may be utilized as a positive correlated predictor.

Keywords: bronchoalveolar lavage fluid; children; drug resistance; hematological malignancies; lower respiratory tract infection; lung microbiome; microbial tolerance; unfavorable environment.