• Welcome to Phoenix Rising!

    Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of and finding treatments for complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.

    To become a member, simply click the Register button at the top right.

ME/CFS Research using Machine Learning - EUROMENE Network Presentation

Messages
14
CC : @Janet Dafoe (Rose49) , @Hip , @Learner1 , @FMMM1 ,@Frenchguy, @JaimeS

Dear All,

As i now have a confirmation from Professor Murovska (Chair of EUROMENE Network), i will be presenting my 5-year Research on ME/CFS and several other syndromes such as Post-Finasteride Syndrome, Post-Accutane Syndrome, Post-treatment Lyme disease Syndrome and Gulf War Ilness Syndrome on September 13th in London on researchers of the EUROMENE Network,

As many of you know, these techniques were able to identify earlier from other Research efforts the importance of Phospholipids, Bile Acid Metabolism and Pyruvate Dehydrogenase.

These methods have also shown that Liver function / Disease may be very closely related to ME/CFS.

Here are the latest algorithmic findings :

-Confirmation of the potential importance of Gut and Gut Microbiome.

-Importance of Butyric Acid and Butyrate. Butyrate has been discussed on a post by @adreno here in PR however the use of Butyric Acid instead of Butyrate should be further investigated. I provide below a number of interesting excerpts regarding Butyric Acid :


Butyric acid, a short-chain fatty acid and one of the main metabolites of intestinal microbial fermentation of dietary fiber, has been shown to have an important role in maintaining the integrity of the intestinal mucosa, while it also has been shown to exert potent anti-inflammatory effects both in vitro and in vivo.

We exposed colonic epithelial cells to butyric acid, then extracted total RNA samples, and subsequently hybridized them to microarray chips. Among the upregulated genes, milk fat globule-epidermal growth factor 8 (MFG-E8) was elevated by approximately fivefold. We previously reported that the potential therapeutic benefits of MFG-E8 in intestinal tissue injury were dependent not only on enhanced clearance of apoptotic cells but also required diverse cellular events for maintaining epithelial integrity. The influence of butyric acid on cell function is often attributed to its inhibition of histone deacetylases (HDACs). We found that acetylation on histone 3 lysine 9 (acetyl-H3K9) around the MFG-E8 promoter was significantly increased with butyric acid exposure


Of interest is the fact that Butyric acid works through MFGE8. Regarding MFGE8 (which has been also found to be important algorithmically) and its association with Gut Lining, Sepsis , Anti-inflammatory action please see the following post :

https://forums.phoenixrising.me/ind...ated-to-sepsis-inflammation-gut-lining.59155/

My goal in the presentation will be to convince researchers to pay particular attention to Liver pathology and to several conditions (such as Hemochromatosis), that affect Liver function (and as a result Bile acid Metabolism, Oxidative Stress Management, Detoxification and many more).

According to the hypothesis discussed, an imperative step is the careful examination and assessment of enterohepatic functioning of ME/CFS patients.

I will post more information regarding Butyric acid, Liver Disease, Gut Dysbiosis and Lining very soon.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
So, what treatments would you suggest the researchers test?

Are you linking liver function to the immune system, infections, the HPA axis, etc.?
 
Messages
14
So, what treatments would you suggest the researchers test?

Are you linking liver function to the immune system, infections, the HPA axis, etc.?

No treatments will be suggested at this stage. The hypothesis suggests that we have an interplay between the Liver and the Gut that may be setting the stage for ME/CFS and several other syndromes as well.

Therefore, my goal would be to turn Researcher's attention to the Liver apart from the Gut , Gut Microbiome and Lining.

There are many papers discussing how Gut dysbiosis is related to Liver issues such as NAFLD, NASH and Fibrosis.

As an example see below :

https://www.ncbi.nlm.nih.gov/pubmed/28927250
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
Yes there are. There are a lot of complexities to this. My experience suggests that treatment may include:
  • Bitters to stimulate bile acid production
  • Detoxification of mycotoxins, heavy metals, organophosphates and other toxins by the liver through support of Phase I and Phase II detoxification
  • The 4 R protocol, or similar, to improve the gut, to allow for Phase III detoxification
The issue is everyone is starting at a different place, and depending on their genes, microbiome composition, and load of toxins, they will need different combinations and doses of treatments. This leads to completely personalized medicine, as Derya Unamatz mentioned in today's Solve/ME/CFS talk, and as is done in functional medicine already today. It is not a "one size fits all" treatment protocol, which is the problem with what is generated in "machine learning" - we are not equal widgets that treatments work or don't - there are many shades of gray...
 

Runner5

Senior Member
Messages
323
Location
PNW
Wow, super interesting. Thank you for putting in the work on this.

I don't understand all the acronyms but look forward to hearing more, maybe you can even do a dumbed down version? :p . I have been reading how CFS / ME could potentially be a metabolic issue - would liver dysfunction also point to this?

Metabolic issues are almost universal in my family tree even going back generations however I don't know anyone else with my GI issues. Plenty of enlarged livers and diabetes but they seem to have cast iron stomachs where as for me - I can't eat OATMEAL. I mean, c'mon GI, oatmeal is like the easiest of all foods right? Oh' well, alas....

I do have to take L-Glutamine and L-Tyrosine consistently and more amino acids if I exercise. I am very curious as to why (just not digesting protein?) and if anyone else even has that issue or ever noticed it.

I'm 43 and this pretty much ruined my life, I have a great life, and I love my life, but I haven't been able to pay my medical bills (this year over $30,000), and I haven't been able to work consistently, or clean my house or take care of myself. I had to cut off all my hair because it kept falling out and I didn't have the energy to groom it or sweep up. I never feel like myself. I am a bubbly outgoing person and CFS / ME makes me hide away, everything is too much.

I have had luck with eating a high fiber nutrient dense diet and avoiding grains and too much fructose but it has only been a few weeks. I believe that would fit with your fiber / butyrate hypothesis. In particular beans seem to be well...a magical fruit. Haha, and I had to go a few days without them and rest my GI and I really noticed a difference, I could barely get out of bed and I slept twice as much. I'm back on the magical fruit. :p

All the best, thank you for your work.
 

Learner1

Senior Member
Messages
6,305
Location
Pacific Northwest
I do have to take L-Glutamine and L-Tyrosine consistently and more amino acids if I exercise. I am very curious as to why
You might be interested in this study, which concludes:

"this study suggests that ME/CFS is associated with PDH impairment, leading to
increased consumption of amino acids that fuel alternative pathways for ATP production."

My labs consistently showed I was short in the amino acids they found to be depleted, and I need about 2g/kg of protein a day for them to normalize.
 

Attachments

  • Fluge Mella amino PDH.pdf
    1.6 MB · Views: 8

ljimbo423

Senior Member
Messages
4,705
Location
United States, New Hampshire
Hi @Themos Kalafatis - These quotes are from the link you posted in your second post-

https://www.ncbi.nlm.nih.gov/pubmed/28927250

The gut liver axis also includes the intestinal permeability (IP) degree. It is very variable and interconnected to several factors, most of them dependent from gut microbiota, that is the "lead" in the control of IP.

For these reasons, it could be useful to intervene, through suitable therapeutic approaches, on the interruption of mechanisms that underlie dysbiosis, IP increase, activation of liver inflammasome, hepatic stellate cells and hepatocarcinogenic processes in order to reduce the liver damage.

I agree with where is says the "most of them dependent from gut microbiota, that is the "lead" in the control of IP."

The gut microbiota can become unbalanced and lead to increased intestinal permeability (IP). There are numerous things that cause or contribute to this, separate from the liver, which most people are exposed to, to varying degrees, often consistently.

#1 is antibiotics, bad diet, food poisoning and food allergies/sensitivities, parasites, viral gut infections, excessive drinking, excessive exercise, non steroidal anti-inflammatory drugs, excessive stress, pesticides, heavy metals, many other toxins and other things.

All of these things cause or contribute to dysbiosis and increased IP. Increased IP allows lipopolysaccharides (LPS) from the gut into the blood and directly to the liver for detoxification.

Lipopolysaccharides are highly toxic and cause enormous amounts of oxidative stress, which can and would wipe out many antioxidants in the liver, eventually depleting them and causing it to function poorly.

I think it's the LPS from increased IP that causes the liver dysfunction, that can to some degree, perpetuate the cycle but I don't see the liver as the primary cause of gut dysfunction in ME/CFS, I see it as secondary.

This is where many thousands of hours of research has lead me, in the last 11-12 years.

Jim
 

Richard7

Senior Member
Messages
772
Location
Australia
@Themos Kalafatis just a couple of things,

1) In this podcast https://peterattiamd.com/domdagostino/ D'agostino mentions that we naturally have a ratio of 1:9 L to D BHB in our serum. Both L And D forms work to suppress inflammation but the L form has a longer half life. I do not know if this is worth doing, I do not understand enough of the chemistry and am way out of my depth, but it would seem that taking a commercially available racemic BHB salt could be a good idea. And that if it was not D'agostino could be a good person to talk to about the various chemicals he has tested.

I am really not all that sure about ketone bodies, I have more energy in ketosis but get more anxiety and hyperacusis and so on, and am not sure if BHB is better than the propionate that armstrong and McFabe are concerned about. I do not really have the head for working through the science at the moment.

2) on the much lower level on which I operate the importance of the liver seems likely.

I know that on my early pathology I was found to not be releasing bile. I have tried all the things that people without ME/CFS use to try to get bile flowing and the only thing that I have found to work is eating liver every day or two. A gap of three days leaves me with food-coloured stools, no trace of bile at all.

I have tried supplementing with things that livers contain that might be the missing link (taurine, glycine, vitamins) but I assume now that it is some product or combination of products that are not essential or particularly noteworthy in people without ME/CFS. This seems likely given Chris Armstrong's model.)

I know that some people have reported considerable improvement when using FIR saunas, mould avoidance and so on: detox and toxin avoidance. The FIR sauna can be in part explained by allowing a population that does not often sweat and often has cold extremities to, change these things and use these methods for getting rid of toxins.

Myhill has info on this, and has evidence from fat biopsies of high levels of toxins in pwme/cfs and of course of dyestuffs and other toxins one might have hoped that the liver would deal with adhering to pwme/cfs's mitochondria.

But the high toxic loads in people's body fat could be explained by exposure or poor liver function. And in my case with no bile production for about 15yrs you would expect a toxin build up. I also know that when I loose weight (FAT) my inflammation goes down, breath out plenty of acetone and have more energy but my PoTS, digestion, hyperacusis, palpitations and anxiety get much much worse.

I do not know if it went anywhere but Mark Van Ness at workwell mentioned doing some work on impaired autonomic function in livers in a video presentation a few years ago. He was looking at glucose release into the blood but he may have some more general ideas about what is going wrong.
 
Messages
14
@ljimbo423

I cannot attribute as a cause of ME/CFS either the Liver or the Gut at this point. However the fact is that Bile Acid Metabolism affects the Gut Microbiome. This means that if we have impaired Bile acid metabolism, Gut Dysbiosis most likely occurs, which means that if any event stresses the Liver, Bile production may be affected (and we have Gut Dysbiosis as an end result).

In other words i see two routes that could cause issues. As @Learner1 asked into another post, we then need to know why ME/CFS Patients fall into a vicious circle of so many Symptoms. I hypothesise that ME/CFS patients have a combination of issues in several pathways that sets this vicious circle on.

@Learner1
BCAAs is a topic that i do not know at all unfortunately.

@Richard7
Thank you, i will have a look at the info you provided.
 
Messages
14
Here is a new post that discusses the possible connection of the Gut Microbiome, Bile Acid Metabolism and Liver pathology. Note that Oxidative Stress and Endoplasmic Reticulum Stress (Topics that have been also previously been identified) are being mentioned.

I also discuss why Butyric acid may be of particular interest to ME/CFS Patients :

http://algogenomics.blogspot.com/2018/07/gut-microbiome-bile-acids-and-butyric.html
 
Last edited by a moderator:
Messages
14
Two new papers suggest the importance of Gut, Bile Acids and Liver function to Psoriasis and Alzheimer's Disease :

Is psoriasis a bowel disease? Successful treatment with bile acids and bioflavonoids suggests it is
P. Haines Ely, MD⁎


VA North California Health Care System, Mather, CA
University of California Davis School of Medicine, Sacramento, CA Department of Dermatology, Sacramento VA Medical Center, Mather, CA


Abstract The gut is the largest lymphoid organ in the body. The human microbiome is composed of trillions of bacteria. The DNA of these bacteria dwarfs the human genome. Diet and ethanol can cause rapid shifts in the number and types of bacteria in the gut. The psoriatic microbiome is similar to that seen in alcoholics; there is a decrease in bacterial diversity and overgrowth of bacteria in the small bowel. Psoriatics often have liver disease and deficiencies in bile acids. Psoriasis is a disease characterized by a leaky gut. All of the comorbidities of this disease are due to systemic endotoxemia. Bacterial peptidoglycans absorbed from the gut have direct toxic effects on the liver and skin. Their absorption, as well as endotoxin absorption, must be eliminated to treat psoriasis successfully. Endotoxin absorption is markedly increased by ethanol and peppers. Bioflavonoids, such as quercetin and citrus bioflavonoids, prevent this absorption. Bile acids, given orally, break up endotoxin in the intestinal lumen. Pathogens, including Helicobacter pylori and Streptococcus pyogenes, must be eliminated with antimicrobial therapy for any treatment to work. A complete protocol for curing psoriasis is provided.

Link : https://www.ncbi.nlm.nih.gov/pubmed/29908580


and


Four new studies being presented at the Alzheimer’s Association International Conference (AAIC) 2018 in Chicago today (Tuesday 24 July) have highlighted a link between the action of the gut and liver, and brain changes associated with Alzheimer’s disease.
  • Fat production in the liver and the link to Alzheimer’s risk
  • Bile acid levels associated with key Alzheimer’s brain changes
  • Liver and gut activity and Alzheimer’s risk genes
  • Circulating fats and their link to the brain

https://www.alzheimersresearchuk.org/new-findings-link-activity-gut-liver-alzheimers-risk/
 

wigglethemouse

Senior Member
Messages
776