Deficient capacity in the gut microbiome is associated with fatigue symptoms in ME/CFS

Posted on: 8th February, 2023

Authors:Cheng Guo, Xiaoyu Che, Thomas Briese, Amit Ranjan, Orchid Allicock, Rachel A Yates, Aaron Cheng, Dana March, Mady Hornig, Anthony L Komaroff, Susan Levine, Lucinda Bateman, Suzanne D Vernon, Nancy G Klimas, Jose G Montoya, Daniel L Peterson, W Ian Lipkin, Brent L William

PMID: 36758522

Abstract

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained debilitating fatigue, cognitive dysfunction, gastrointestinal disturbances, and orthostatic intolerance. Here, we report a multi-omic analysis of a geographically diverse cohort of 106 cases and 91 healthy controls that revealed differences in gut microbiome diversity, abundances, functional pathways, and interactions. Faecalibacterium prausnitzii and Eubacterium rectale, which are both recognized as abundant, health-promoting butyrate producers in the human gut, were reduced in ME/CFS. Functional metagenomics, qPCR, and metabolomics of fecal short-chain fatty acids confirmed a deficient microbial capacity for butyrate synthesis. Microbiome-based machine learning classifier models were robust to geographic variation and generalizable in a validation cohort. The abundance of Faecalibacterium prausnitzii was inversely associated with fatigue severity. These findings demonstrate the functional nature of gut dysbiosis and the underlying microbial network disturbance in ME/CFS, providing possible targets for disease classification and therapeutic trials.