Biology subjects

Siranosian, B. A.

Publications and source records attributed to Siranosian, B. A..

3 recordsLinked to original sources

bioRxiv2022

The TaxUMAP atlas: efficient display of large clinical microbiome data reveals ecological competition involved in protection against bacteremia

The microbiome is associated with health and disease, but causal effects are hard to quantify-- especially in humans where controlled experiments are nearly impossible. Akin to natural experiments, closely monitored patients offer an alternative to characterize microbiome effects. We present TaxUMAP, a taxonomically-informed visualization method to effectively display diverse microbiome states. TaxUMAP charts a microbiome atlas from 1,870 cancer patients as they progress through therapy-induced perturbations, and quantifies the microbiome contribution to patients risk for life-threatening bacteremia. We find that the lowest diversity states (gut dominations) that follow antibiotic treatments are stable, and that diverse communities harbor more diverse antimicrobial resistance genes than dominations. We reveal that certain Klebsiella species are associated with reduced risk for bacteremia, an effect driven by bacterial competition that we validate experimentally in vitro and in vivo. TaxUMAP effectively maps longitudinal microbiome data that can facilitate research into causal microbiome effects on human health. HIGHLIGHTSO_LITaxUMAP charts an atlas of patients microbiome states and their clinical context to reveal new causal effects. C_LIO_LIAntibiotics deplete the biodiversity and reduce the number of different antimicrobial resistance genes in the gut microbiome. C_LIO_LICertain Klebsiella species are associated with lower risk of bacteremia by other gut-borne pathogens. C_LIO_LIThese Klebsiella outcompete other gram-negative pathogens in vivo. C_LI

microbiology↗

bioRxiv2021

A compilation of fecal microbiome shotgun metagenomics from hospitalized patients undergoing hematopoietic cell transplantation

Hospitalized patients receiving hematopoietic cell transplants provide a unique opportunity to study how the human gut microbiome changes in response to perturbations, and how the resulting changes in the microbiome feedback on its living host. We previously compiled a large-scale longitudinal dataset of stool microbiome compositions from these patients and associated metadata1. In that dataset the microbiome analysis was limited to the taxonomic composition of the bacterial population obtained from 16S rRNA gene sequencing. Here, we augment those data with shotgun metagenomic sequences from a nested subset of 395 stool samples. We provide accession numbers that link each sample to the paired-end sequencing files deposited in a public repository, which can be directly accessed by the online services of PATRIC2 to be analyzed without the users having to download or transfer the files. We provide examples that show how shotgun sequencing enriches microbiome analyses beyond the taxonomic composition such as the analysis of gene functions including virulence factors and antibiotic resistances, and the assembly of genomes from metagenomic data.

systems biology↗

bioRxiv2021

Rare transmission of commensal and pathogenic bacteria in the gut microbiome of hospitalized adults

Bacterial bloodstream infections are a major cause of morbidity and mortality among patients undergoing hematopoietic cell transplantation (HCT). Although previous research has demonstrated that pathogenic organisms 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. We hypothesized that patient-patient transmission may be responsible for pathogens colonizing the microbiome of HCT patients, and that patients who share time and space in the hospital are more likely to share bacterial strains. Here, we used 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 five years. We used metagenomic assembly and strain-specific comparison methods to investigate transmission of gut microbiota between individuals. While patients who shared time and space in the hospital did not converge in overall microbiome composition, we did observe four pairs of patients who harbor identical or nearly identical E. faecium strains in their microbiome. These strains may be the result of transmission between patients who shared a room and bathroom, acquisition from a common source in the hospital or transmission from an unsampled source. We also observed identical Akkermansia muciniphila and Hungatella hathewayi strains in two pairs of patients. In both cases, the patients were roommates for at least one day, the strain was absent in the putative recipients microbiome prior to the period of roommate overlap and the putative recipient had a microbiome perturbed by antibiotic treatment for a bloodstream infection. Finally, we identified multiple patients who harbored identical strains of several species commonly found in commercial probiotics and dairy products, including Lactobacillus rhamnosus, Lactobacillus gasseri and Streptococcus thermophilus. Overall, our findings indicate that pathogenic organisms from a single source are not frequently colonizing the gut microbiome of multiple patients. However, the potential transmission of commensal microbes with immunomodulatory properties raises questions about the recovery of microbiome diversity after HCT, and indicates that patients in this setting may acquire new microbes by sharing space with others.

microbiology↗