Abstract

Bacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT). Although previous research has demonstrated that pathogens may translocate from the gut microbiome into the bloodstream to cause infections, the mechanisms by which HCT patients acquire pathogens in their microbiome have not yet been described. Here, we use linked-read and short-read metagenomic sequencing to analyze 401 stool samples collected from 149 adults undergoing HCT and hospitalized in the same unit over three years, many of whom were roommates. We use metagenomic assembly and strain-specific comparison methods to search for high-identity bacterial strains, which may indicate transmission between the gut microbiomes of patients. Overall, the microbiomes of patients who share time and space in the hospital do not converge in taxonomic composition. However, we do observe six pairs of patients who harbor identical or nearly identical strains of the pathogen Enterococcus faecium, or the gut commensals Akkermansia muciniphila and Hungatella hathewayi. These shared strains may result from direct transmission between patients who shared a room and bathroom, acquisition from a common hospital source, or transmission from an unsampled intermediate. We also identify multiple patients with identical strains of species commonly found in commercial probiotics, including Lactobacillus rhamnosus and Streptococcus thermophilus. In summary, our findings indicate that sharing of identical pathogens between the gut microbiomes of multiple patients is a rare phenomenon. Furthermore, the observed potential transmission of commensal, immunomodulatory microbes suggests that exposure to other humans may contribute to microbiome reassembly post-HCT.

Highlights

  • Bacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT)

  • Research from our group and others has shown that strains of bacteria isolated from the blood of HCT patients with bloodstream infections (BSIs) may be indistinguishable from the strains in the intestinal microbiota of these patients prior to infection[3,4,5]

  • We focused further analysis on E. coli and E. faecium, as these species are both frequently detected in stool and frequently cause BSIs

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Summary

Introduction

Bacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT). We do observe six pairs of patients who harbor identical or nearly identical strains of the pathogen Enterococcus faecium, or the gut commensals Akkermansia muciniphila and Hungatella hathewayi These shared strains may result from direct transmission between patients who shared a room and bathroom, acquisition from a common hospital source, or transmission from an unsampled intermediate. While the bacterial pathogens that cause BSIs in HCT patients are well understood, their routes of transmission are often unclear Determining these transmission pathways involves identifying two critical elements: the source of the infection, i.e., how the pathogen was introduced into the patient’s bloodstream, and the origins of the particular pathogen causing the BSI. Transmission of gut microbiota is thought to occur by a fecal–oral route, which could happen in the hospital environment by exposure to contaminated surfaces or equipment, sharing a room or bathroom, contaminated hands of healthcare workers, or other sources. The perturbed microbiomes of HCT patients, often lacking key species to provide colonization resistance, may be primed to acquire new species from these sources

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