The Nasal Microbiome As a Predictor of Infectious Complications after Hematopoietic Cell Transplant Patients

Abstract

<h3>Introduction</h3> Hematopoietic cell transplantation (HCT) is a potentially curative treatment for a range of malignant and nonmalignant disorders. A common complication of HCT is the mucosal barrier injury that enables commensal microbes to invade underlying tissues and the bloodstream causing infections during the transplant period. Additionally, antibiotic use has a dramatic impact on the respiratory and intestinal microbiome by reducing the density and diversity of commensal flora and thus increasing the risk of acquiring drug resistant pathogens. <h3>Objectives</h3> To distinguish patients at risk of developing infections using nasal microbiome data and to evaluate the relationship of the nasal microbiome and different types of infections in the HCT population at our institution. <h3>Methods</h3> We conducted a prospective observational study. A total of 50 HCT patients were enrolled and blood, nasal washes and clinical data were collected at the preconditioning period (from day -14 of HCT up to 24 hours following initiation of conditioning regimen), every week for 8 weeks and every other week until week 14 post-HCT. Microbiome abundance prior to the infection's onset was analyzed. <h3>Results</h3> Patients were on average 56 years of age (range: 20-73) and the majority were white (n=40, 80%), male (n=34, 68%) and had leukemia (68%). Overall, patients experiencing any kind of infections had a different nasal microbiome than those without. An abundance of Stenotrophomonas in their nasal microbiome was associated with urinary tract infections and respiratory viral infections (FDR-Adj P value=0.009 and 0.004, respectively). Bacterial pneumonia occurred after an increase in Capnocytophaga was seen in the nasal microbiome (FDR-Adj P value=0.009) whereas fungal pneumonia occured after an increase in Pseudomonas, Methylobacterium, Lachnoclostridium, and Lactobacillus (FDR-Adj P value=0.01). Clostridium difficile gut colonization was observed following an increase in Dolosigranulum and Muribaculaceae in the nasal microbiome (FDR-Adj P value<0.0001) whereas Vancomycin-resistant enterococci colonization occurred after an increase in Muribaculaceae, Oblitimonas, Ignatzschineria, Lactobacillus, and Sporosarcina (FDR-Adj P value<0.007) (Figure). <h3>Conclusion</h3> Our findings provide important information on specific operational taxonomic unit abundances in the nasal microbiome and infections. The nasal microbiome could be key to predict infections in HCT recipients and design future interventions to prevent and reduce the morbidity and mortality related to infections in these high risk patients.