1. Guest, the 'News in Brief' for the week beginning 19th September 2022 is here.
    Dismiss Notice
  2. Welcome! To read the Core Purpose and Values of our forum, click here.
    Dismiss Notice

Preprint: Multi-omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2021, Xiong

Discussion in 'ME/CFS research' started by Andy, Oct 29, 2021.

  1. Andy

    Andy Committee Member

    Messages:
    17,469
    Location:
    Hampshire, UK
    Abstract

    Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, multi-system, debilitating disability manifesting as severe fatigue and post-exertional malaise. The chronic dysfunctions in ME/CFS are increasingly recognized as significant health factors with potential parallels with "long COVID". However, the etiology of ME/CFS remains elusive with limited high-resolution human studies. In addition, reliable biomarker-based diagnostics have not been well-established, but may assist in disease classification, particularly during different temporal phases of the disease.

    Here, we performed deep multi-omics (shotgun metagenomics of gut microbiota and plasma metabolomics) and clinical phenotyping of healthy controls (n=79) vs. two cohorts of ME/CFS patients: those with short-term disease (<4 years, n=75), and patients with long-term disease (>10y, n=79). Overall, ME/CFS was characterized by reduced gut microbiome diversity and richness with high heterogeneity, and depletion of sphingomyelins and short-chain fatty acids in the plasma. We found significant differences when stratifying by cohort; short-term ME/CFS was associated with more microbial dysbiosis, but long-term ME/CFS was associated with markedly more severe phenotypic and metabolic abnormalities.

    We identified a reduction in the gene-coding capacity (and relative abundance of butyrate producers) of microbial butyrate biosynthesis together with a reduction in the plasma concentration of butyrate, especially in the short-term group. Global co-association and detailed gene pathway correlation analyses linking the microbiome and metabolome identified additional potential biological mechanisms underlying host-microbiome interactions in ME/CFS, including bile acids and benzoate pathways.

    Finally, we built multiple state-of-the-art classifiers to identify microbes, microbial gene pathways, metabolites, and clinical features that individually or together, were most able to differentiate short or long-term MECFS, or MECFS vs. healthy controls.

    Taken together, our study presents the highest resolution, multi-cohort and multi-omics analysis to date, providing an important resource to facilitate mechanistic hypotheses of host-microbiome interactions in ME/CFS.

    Open access, https://www.biorxiv.org/content/10.1101/2021.10.27.466150v1
     
    Midnattsol, janice, Hutan and 15 others like this.
  2. Andy

    Andy Committee Member

    Messages:
    17,469
    Location:
    Hampshire, UK
    JAX Research on Microbiome Changes in Short- and Long-Term ME/CFS is now Available Online

    We are very excited to announce that in collaboration with the lab of Julia Oh at The Jackson Laboratory, which studies the microbiome in ME/CFS for the JAX CRC, we have just posted the full preprint of our new ME/CFS microbiome paper on BioRxiv, which will continue to be updated following reviewer comment and peer-review. In this detailed study led by Ruoyun Xiong, we did deep multi-omics, where we performed shotgun metagenomics of the gut microbiota and plasma metabolomics in 79 healthy controls and two cohorts of ME/CFS patients: 75 with short-term disease (<4 years), and 79 patients with long-term disease (>10 years). We also correlated these data to clinical information collected from subject questionnaires, and built multiple state-of-the-art classifiers that were able to differentiate short or long-term ME/CFS from each other, or ME/CFS from healthy controls.

    https://jaxmecfs.com/2021/10/29/jax...and-long-term-me-cfs-is-now-available-online/
     
    Midnattsol, janice, Hutan and 6 others like this.
  3. Creekside

    Creekside Senior Member (Voting Rights)

    Messages:
    370
    I'm sure my microbiome would be abnormal. There are so many foods and food families I need to avoid that my food diversity is greatly reduced. For many PWME, reduced activity levels might also affect the microbiome. Studies such as this really should use controls with similarly reduced dietary variability and activity levels.
     
    Hutan likes this.
  4. Creekside

    Creekside Senior Member (Voting Rights)

    Messages:
    370
    I came across this news item just after reading this thread, and it seems to fit it: https://newatlas.com/health-wellbeing/microbiome-gut-bacteria-inflammation-colitis-pgp/

    "But more recently P-gp has been found to also play a key anti-inflammatory role in the gut, producing molecules known as endocannabinoids which suppress inflammation.

    In cases of chronic intestinal inflammation, such as ulcerative colitis, P-gp expression is reduced. And in those cases of intestinal inflammation researchers also detected major imbalances in gut bacteria populations. But before now it hasn’t been clear exactly how the microbiome could be influencing P-gp expression.

    The new research found P-gp expression is influenced by a combination of gut bacteria metabolites. Most importantly the research found P-gp expression is not regulated by one single metabolite or species of bacteria. Instead, P-gp expression is induced by a synergistic combination of a short-chain fatty acid known as butyrate and three secondary bile acids (LCA, DCA, and UDCA).

    Optimal P-gp expression was detected only when all of these molecules were working in concert with one another. Merran Dunford, a researcher from the University of Bath working on the study, says the big finding here is the discovery of a cross-talk mechanism highlighting how a healthy microbiome can communicate with the immune systems to keep inflammatory activity in the gut in balance."
     
    Michelle, janice and Hutan like this.
  5. Midnattsol

    Midnattsol Moderator Staff Member

    Messages:
    2,338
    This! So much this. And include a dietitician when reviewing people's diet.

    This post has been copied, and replies moved, to the thread "Can dieticians (dietitians) help with ME/CFS?".
     
    Last edited: Nov 2, 2021
    Michelle, Hutan and Trish like this.
  6. dreampop

    dreampop Senior Member (Voting Rights)

    Messages:
    410
    I have very little interest in the microbiome at this point. It's interesting to see that sphingomyelins and short-chain fatty acids appear again, they were prominent in some previous metablomics studies.
     
  7. Andy

    Andy Committee Member

    Messages:
    17,469
    Location:
    Hampshire, UK
    Seems to me that the question that will need to be answered (if it hasn't been already) is "are these changes due to the ME or 'just' due to being ill". Looking at whatever similar research has been done in other illnesses will be important before accepting these results as ME-specific.
     
    janice, Michelle, Ron and 3 others like this.
  8. FMMM1

    FMMM1 Senior Member (Voting Rights)

    Messages:
    1,898
    Yea consequence or cause? If it's consequence then presumably you need to understand what's upstream. If it's cause then it's more interesting; Chris Armstrong (from memory) put forward the theory (webinar 2015?) that gut dysbiosis was maintaining the disease state - bi-stability if you like.

    I'm guessing that this paper is suggesting gut dysbiosis is the cause.
     
    janice likes this.

Share This Page