Multi-'omics of gut microbiome-host interactions in short- and long-term myalgic encephalomyelitis/chronic fatigue syndrome patients.

Document Type

Article

Publication Date

2-8-2023

Keywords

JGM, SS1, Humans, Fatigue Syndrome, Chronic, Gastrointestinal Microbiome, Dysbiosis, Metabolomics, Feces

JAX Source

Cell Host Microbe. 2023;31(2):273-87.e5.

ISSN

1934-6069

PMID

36758521

DOI

https://doi.org/10.1016/j.chom.2023.01.001

Grant

This work was funded by 1U54NS105539. J.O. is additionally supported by the NIH (1 R01 AR078634-01, DP2 GM126893-01, 1 U19 AI142733, and 1 R21 AR075174).

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, debilitating disorder manifesting as severe fatigue and post-exertional malaise. The etiology of ME/CFS remains elusive. Here, we present a deep metagenomic analysis of stool combined with plasma metabolomics and clinical phenotyping of two ME/CFS cohorts with short-term (<4 >years, n = 75) or long-term disease (>10 years, n = 79) compared with healthy controls (n = 79). First, we describe microbial and metabolomic dysbiosis in ME/CFS patients. Short-term patients showed significant microbial dysbiosis, while long-term patients had largely resolved microbial dysbiosis but had metabolic and clinical aberrations. Second, we identified phenotypic, microbial, and metabolic biomarkers specific to patient cohorts. These revealed potential functional mechanisms underlying disease onset and duration, including reduced microbial butyrate biosynthesis and a reduction in plasma butyrate, bile acids, and benzoate. In addition to the insights derived, our data represent an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS.

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