Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue..., 2023, Guo,Lipkin et al

Andy

Andy

Retired committee member
Study now published, see https://www.s4me.info/threads/prepr...toms-2021-guo-lipkin-et-al.23117/#post-459929 for abstract and link.

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
 
Last edited:
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.
 
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.
 
I was just looking through the threads tagged with butyrate and noticed this interesting one posted by @alicec:
Extensive impact of non-antibiotic drugs on human gut bacteria (2018) Maier et al

They screened non-antibiotic drugs taken by humans against a range of bacterial species in the gut microbiome. they found 27% of the drugs they screened had an antibiotic effect, including antipsychotics.

They also found that human-targeted drugs had an impact on major butyrate producers:
Overall, species with higher relative abundance across healthy individuals were significantly more susceptible to human-targeted drugs (P=0.0012 based on Spearman correlation; Fig. 1c). This suggests that human-targeted drugs have an even larger impact on the gut microbiome, with key species related to healthy status15, such as major butyrate producers (E. rectale, R. intestinalis, Coprococcus comes) and propionate producers (B. vulgatus, Prevotella copri, Blautia obeum) 16, and enterotype drivers (P. copri) 17, being relatively more affected.
Click to expand...

So, it gets very hard to unravel what is causing what.

This Lipkin study only controlled for antibiotic use in the 6 weeks prior to sampling.
 
Screen Shot 2021-11-02 at 12.05.47 PM.png

I'm not sure how important the differences in abundances are - here are graphs from the paper for two key species. Green on the left is controls, red on the right is ME/CFS. There's a lot of overlap and the average isn't very different, even though the p value suggests a difference.

Maybe it's worth carefully going through the paper, but I haven't.
 
The worst part is you could likely get adequate information about the diet for this type of study from a semiquantitative food questionnaire with foods that are known to feed the "positive" bacteria. So including starchy roots and tubers (maybe also how they are prepared as cooked + cooled down is most beneficial in this instance sine the cooling process make the starches into resistant starch that the bacteria enjoy), cruciferous vegetables, fodmaps, white or whole grain products, legumes, nuts, (fatty) fish, supplements (I would ask for omega-3's specifically, not just prebiotics) and maye some others but these were at the top of my head. By seeing if they are being eaten 1-3 times a day, 1-3 times a week etc you likely could see if the pwME have a different diet than the controls (and this is seen in many chronic conditions as preparing and eating food, not least shopping itself, takes energy the patient doesn't have).

If doing a questionnaire like that is too much effort for the patient group (which could be the case here), there are online solutions that even provide pictures to illustrate different amounts of food, which possibly could be tailored so the participant could save and return to it later.

Study result section said:
Of other covariates, only subject age showed a significant positive association with all three alpha diversity metrics. These results suggest that differences in alpha diversity are associated with sr-IBS rather than ME/CFS and highlight the importance of assessing IBS as a potential confounder of microbiota differences in ME/CFS.
Click to expand...
People of different ages also often have statistically significant different intakes of various foods like starchy tubers, fish, vegetables in general.. :whistle:

Even though more pwME than controls took prebiotic supplements, this does not mean they consumed more prebiotics overall. So I don't feel this is warranted:
Discussion said:
The observation that ME/CFS subjects had lower levels of BPB and butyrate and higher total bacterial load even with adjustment of regression models for prebiotic fiber use, suggests that some factor, either associated with the pathobiology or symptoms of ME/CFS, rather than prebiotic fiber intake is selectively influencing these microbiome changes.
Click to expand...

They write that no pwME were acutely malnourished, but not how this was screened for. Malnourishment in illness populations are not uncommon, especially not with energy limiting diseases. From my point of view, ME increases risk of inadequate dietary intake in line with other illnesses although I have never seen the illness on a list of "increased risk" illnesses. When in PEM I would fit neatly into the category of an "at risk patient" with neurological disease (trouble to shop, prepare and eat food due to low stamina/low energy/muscle weakness, low appetite, nausea).

Less butyrate producing bacteria is not unique to pwME, and associations with between butyrate-producing bacteria and fatigue could come from the fact that the food that boost butyrate production also include numerous other beneficial compounds, which when low in the diet could contribute to fatigue. I am a fan of butyrate, I just don't like that this point often is not taken into account :)
 
Now published.

Full title: Deficient butyrate-producing capacity in the gut microbiome is associated with bacterial network disturbances and fatigue symptoms in ME/CFS

Highlights
  • ME/CFS patients have substantial gut microbiome dysbiosis
  • Bacterial abundances, functions, SCFAs and species interactions deviate in ME/CFS
  • Reduced F. prausnitzii and E. rectale in ME/CFS may contribute to butyrate deficiency
  • Low F. prausnitzii abundance correlates with more severe fatigue symptoms in ME/CFS
Summary
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.

Open access, https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(23)00029-X
 
Last edited:
NIH news release. Article covers both this study and Preprint: Multi-omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), 2021, Xiong

Studies find that microbiome changes may be a signature for ME/CFS

"Researchers have found differences in the gut microbiomes of people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) compared to healthy controls. Findings from two studies, published in Cell Host & Microbe and funded by the National Institutes of Health add to growing evidence that connects disruptions in the gut microbiome, the complete collection of bacteria, viruses, and fungi that live in our gastrointestinal system, to ME/CFS.

“The microbiome has emerged as a potential contributor to ME/CFS. These findings provide unique insights into the role the microbiome plays in the disease and suggest that certain differences in gut microbes could serve as biomarkers for ME/CFS,” said Vicky Whittemore, Ph.D., program director at NIH’s National Institute of Neurological Disorders and Stroke (NINDS)."

https://www.nih.gov/news-events/news-releases/studies-find-microbiome-changes-may-be-signature-mecfs
 
My ME didn't start until I was put on a "skookum" dose of penicillin for a tooth infection. Three days later the ME hit in a split second and I've never been the same since. I've always believed that my ME was due to a screwed up gut biome.
 
You must log in or register to reply here.
Back
Top Bottom