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Updated: Jul 6, 2025

Purifying the Impure: Sequencing Metagenomes and Metatranscriptomes from Complex Animal-associated Samples

Purifying the Impure: Sequencing Metagenomes and Metatranscriptomes from Complex Animal-associated Samples

Published on: December 22, 2014

Host and Microbe Blood Metagenomics Reveals Key Pathways Characterizing Critical Illness Phenotypes.

Lucile P A Neyton¹, Pratik Sinha², Aartik Sarma¹

¹Division of Pulmonary, Critical Care, Allergy and Sleep Medicine.

American Journal of Respiratory and Critical Care Medicine

|January 8, 2024

Summary

Sepsis presents as hyperinflammatory or hypoinflammatory phenotypes with distinct immune gene expression and microbial differences. Understanding these sepsis phenotypes may guide precision treatment strategies for better patient outcomes.

Keywords:

pathogens phenotypes sepsis transcriptomics

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Published on: January 10, 2025

Area of Science:

Immunology
Genomics
Microbiology

Background:

Two sepsis phenotypes, hyperinflammatory and hypoinflammatory, are known but their biological differences are poorly understood.
These phenotypes have divergent clinical outcomes and treatment responses.

Purpose of the Study:

To investigate biological differences between sepsis phenotypes using host and microbe metagenomic data.
To assess concordance between identified phenotypes and other established sepsis/ARDS classifications.

Main Methods:

Analysis of host and plasma metagenomic sequencing data from 189 sepsis patients (113 hypoinflammatory, 76 hyperinflammatory).
Latent class analysis was previously used for phenotype assignment.
Comparison with existing sepsis (SRS1-2, MARS1-4) and ARDS (reactive, uninflamed) molecular subtypes.

Main Results:

Significant differential gene expression (5,755 genes) between hyperinflammatory (innate immune genes) and hypoinflammatory (adaptive/T cell genes) sepsis phenotypes.
Distinct microbial profiles, with increased Enterobacteriaceae in hyperinflammatory sepsis.
Observed overlap with previously identified sepsis and ARDS transcriptional subtypes.
Corticosteroids may negatively impact hypoinflammatory sepsis patients.

Conclusions:

Hyperinflammatory and hypoinflammatory sepsis phenotypes possess distinct transcriptional and metagenomic characteristics.
These findings support the potential for developing precision treatment strategies tailored to individual sepsis phenotypes.