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Researchers Tie Some Bloodstream Infections to the Gut Microbiome

NEW YORK (GenomeWeb) – Using a new bioinformatic tool they developed, Stanford University researchers traced the origin of some patients' bloodstream infections to their gut microbiome.

Bloodstream infections are common among hospital patients, but clinicians cannot always tell where these infections come from, making it difficult to prevent their development. The Stanford team developed a tool dubbed StrainSifter that compares pathogens isolated from the bloodstream to potential sources.

As they reported today in Nature Medicine, the researchers applied this approach to examine bloodstream infections in patients and compare them to their stool microbiomes. For nearly half the patients, they found that the strains circulating in their blood were highly similar to strains also found in their gut, including strains not typically thought to be enteric in origin.

"With these powerful genomic tools, we anticipate that precision source identification and strain tracking will lead us to a new, sharpened model of infectious disease," Stanford's Ami Bhatt and her colleagues wrote in their paper.

The researchers performed a retrospective cohort study of patients who had undergone either autologous or allogeneic hematopoietic cell transplantation — a population that is prone to bloodstream infections. In all, 30 patients with 32 bloodstream isolates were included in the study, all of whom had had stool samples collected in the 30 days prior to developing a blood infection.

A median two stool samples per patient, collected a median nine days before infection, underwent sequencing, as did bloodstream isolates and stool samples collected post-infection.

After taxonomically classifying the sequencing data they generated using the One Codex platform, the researchers found that the species behind the bloodstream infection reached a relative abundance of 0.1 percent or more in the stool for 47 percent of the species. Two species, typically gut-dwelling ones, were more abundant in the patients' gut even before the onset of infection.

This, however, didn't show whether the strain behind the bloodstream infection was the same as the gut strain. So, the researchers used their StrainSifter tool to examine the relatedness between the isolates from the blood and the metagenome.

The bioinformatic tool specifically determines whether an organism is present based on the inputted short read data and generates phylogenetic trees and SNV counts between samples. In this study, the researchers compared the phylogenetic relatedness of the bloodstream infection and stool sample stains to one another as well as to publicly available data.

Overall, they found that both blood and gut strains from the same person were more closely related to each other than to strains from other individuals. Further, bloodstream isolates and gut strains of species like Escherichia coli, Enterococcus faecium, Klebsiella pneumoniae, and Streptococcus mitis — all gut organisms — were closely related. One patient who was sampled at three time points prior to infection had no SNV differences in the E. coli strains present, suggesting it was present for more than a month before infection.

The researchers also found closely related gut and bloodstream infection strains even among non-enteric-origin organisms. For one patient, they found one SNV difference between blood and gut Staphylococcus epidermidis, and found no SNV differences between blood and gut P. aeruginosa in another patient.

In all, the researchers said their findings suggested that the gut microbiome could be a source of pathogens that infect the bloodstream, including of pathogens generally thought to be non-enteric.

"This knowledge may complement the growing body of research on therapies to improve gut microbiota diversity and may inform attempts to bolster colonization resistance against pathogens," the authors wrote.