Preprint: Deficient butyrate-producing capacity in the gut microbiome of [ME/CFS] patients is associated with fatigue symptoms, 2021, Guo,Lipkin et al

Abstract
Background: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a complex, debilitating disease of unknown cause for which there is no specific therapy. Patients suffering from ME/CFS commonly experience persistent fatigue, post-exertional malaise, cognitive dysfunction, sleep disturbances, orthostatic intolerance, fever and irritable bowel syndrome (IBS). Recent evidence implicates gut microbiome dysbiosis in ME/CFS. However, most prior studies are limited by small sample size, differences in clinical criteria used to define cases, limited geographic sampling, reliance on bacterial culture or 16S rRNA gene sequencing, or insufficient consideration of confounding factors that may influence microbiome composition. In the present study, we evaluated the fecal microbiome in the largest prospective, case-control study to date (n=106 cases, n=91 healthy controls), involving subjects from geographically diverse communities across the United States.

Results: Using shotgun metagenomics and qPCR and rigorous statistical analyses that controlled for important covariates, we identified decreased relative abundance and quantity of Faecalibacterium, Roseburia, and Eubacterium species and increased bacterial load in feces of subjects with ME/CFS. These bacterial taxa play an important role in the production of butyrate, a multifunctional bacterial metabolite that promotes human health by regulating energy metabolism, inflammation, and intestinal barrier function. Functional metagenomic and qPCR analyses were consistent with a deficient microbial capacity to produce butyrate along the acetyl-CoA pathway in ME/CFS. Metabolomic analyses of short-chain fatty acids (SCFAs) confirmed that fecal butyrate concentration was significantly reduced in ME/CFS. Further, we found that the degree of deficiency in butyrate-producing bacteria correlated with fatigue symptom severity among ME/CFS subjects. Finally, we provide evidence that IBS comorbidity is an important covariate to consider in studies investigating the microbiome of ME/CFS subjects, as differences in microbiota alpha diversity, some bacterial taxa, and propionate were uniquely associated with self-reported IBS diagnosis.

Conclusions: Our findings indicate that there is a core deficit in the butyrate-producing capacity of the gut microbiome in ME/CFS subjects compared to healthy controls. The relationships we observed among symptom severity and these gut microbiome disturbances may be suggestive of a pathomechanistic linkage, however, additional research is warranted to establish any causal relationship. These findings provide support for clinical trials that explore the utility of dietary, probiotic and prebiotic interventions to boost colonic butyrate production in ME/CFS.

Open access, https://www.medrxiv.org/content/10.1101/2021.10.27.21265575v1.full-text

 

https://twitter.com/user/status/1455218346719424518

 

I believe that this preprint shows similar findings to the recent preprint from Jackson Labs, Preprint: Multi-omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2021, Xiong

 

My butyrate-producing bacteria were below normal on my test when I had h pylori infection.

 

I remember back before S4ME came into existence that many people were talking about a new supplement called Miyarisan? Meant to boost butyrate production. Many of us still seem to be around ME forums.

But maybe it's not as simple as that. I hope that they have found something useful and that some kind soul will be able to explain that when the time comes.

 

The impact of butyrate producing bacteria is something that could be tested in a clinical trial. Should be relatively easy to do.

 

I think if it was an effective treatment for ME, someone would have noticed it after taking butyrate supplements. I've had different antibiotics and drastic diet changes, which should have affected my butyrate production, but I didn't notice any significant differences in my ME.

 

Wonder if this might be one reason why FMT sometimes proves successful...?

 

A webinar presentation by Lipkin on these results has been posted here, https://www.s4me.info/threads/usa-nih-national-institutes-of-health-news.18724/page-5#post-405387