My last two post both dealt with ME/CFS patients with high Prevotella copri which is associated with mold. The association of mold to a subset of ME/CFS patients goes back to the last millennium. A man called Erik Johnson was nicked name the “Mold Warrior” and mentioned in articles such as:  Chester Levine “Association of concurrence between sick building syndrome and CFS: Epidemic neurasthenia revisited” [1994] – that is 30 years ago!!! He has a YouTube channel for those who are interested as well as many interviews with him by others.

A mycotoxin is a toxic secondary metabolite / chemical produced by fungi and is capable of causing disease and death in both humans and other animals. A car’s “mycotoxin” is carbon monoxide and other air pollution products.

What is Mold?

We need to tread gently not to overgeneralized or over simplified this. As a starting point: “”the most important mycotoxins associated with human and veterinary diseases, including aflatoxin, citrinin, ergot akaloids, fumonisins, ochratoxin A, patulin, trichothecenes, and zearalenone.” Mycotoxins[2003]. Molds are a group of fungi called “Hyphomycetes“. For many people they are two words for the same thing.

Going over to my favorite definitive source, KEGG: Kyoto Encyclopedia of Genes and Genomes, we get a much more complete list. (Click on the C-link to get more information on each)

Mycotoxins

Aflatoxins

C06800 Aflatoxin B1

C16753 Aflatoxin B2

C16754 Aflatoxin G2

C16755 Aflatoxin G1

C16756 Aflatoxin M1

Trichothecenes

C09662 Diacetoxyscirpenol

C19952 HT-2 Toxin

C09738 T-2 Toxin

C19583 Fusarenone X

C06080 Nivalenol

C09747 Vomitoxin

C20017 Satratoxin H

Fumonisins

C19241 Fumonisin B1

C19242 Fumonisin B2

Ergot alkaloids

C09023 Agroclavine

C09162 Ergocornine

C09164 Ergocristine

C07545 alpha-Ergocryptine

C20590 beta-Ergocryptine

C07543 Ergonovine

C07544 Ergotamine

Indole diterpene alkaloids

C20555 Aflatrem

C20527 Emindole SB

C20600 Janthitrem B

C20601 Janthitrem C

C20551 Lolitrem B

C20530 Paspaline

C20553 Paspalicine

C20554 Paspalinine

C13782 Paxilline

C20070 Penitrem A

C20731 Penitrem B

C20795 Penitrem C

C20596 Penitrem D

C20597 Penitrem E

C20598 Penitrem F

C20599 Pennigritrem

C20546 Terpendole C

Others

C16765 Citrinin

C09955 Ochratoxin A

C16748 Patulin

C09981 Zearalenone

C16838 Alternariol

C08511 Tenuazonic acid

C08441 Tentoxin

C11590 Beauvericin

C15740 Enniatin B

C15757 Enniatin D

C20591 Fusaproliferin

C20592 Moniliformin

C16766 Citreoviridin

C19379 Cyclochlorotine

C03032 Cyclopiazonic acid

C19953 Cytochalasin A

C19954 Cytochalasin B

C10595 Gliotoxin

C16763 Luteoskyrin

C20046 Mollicellin C

C16804 Penicillic acid

C19955 Phomopsin A

C06079 PR-toxin

C16767 Rubratoxin B

C16764 Rugulosin

C16768 Sporidesmin J

C00961 Sterigmatocystin

C20045 Verruculogen

C14752 alpha-Zearalanol

C14750 alpha-Zearalenol

C14751 beta-Zearalenol

These toxins are the product of molds. Different molds produces different ones in different amounts. See Growth of Fungal Cells and the Production of Mycotoxins [2018] for more discussion. One fungi is Candida. There are many more as shown below.

The amount of research is actually very sparse. One rule of thumb (applies to some cases only) is that excessive Prevotella growth may happen from some fungi.

• “Furthermore, the culture supernatants of Candida spp. grown with arabinoxylan promoted rapid proliferation of Prevotella copri. ” Comparison of Japanese and Indian intestinal microbiota shows diet-dependent interaction between bacteria and fungi [2019]
• Evaluation of an oral subchronic exposure of deoxynivalenol on the composition of human gut microbiota in a model of human microbiota-associated rats.  [2013] “significantly increased Bacteroides/Prevotella group and decreased concentration levels for Escherichia coli.”

Different mycotoxins may cause increase or decrease of different bacteria. This is made worse in clinical practice because only a few may be tested for.

Literature Review

• There are a number of article on the impact on the gut (for example “leaky gut”)
  • The Compromised Intestinal Barrier Induced by Mycotoxins [2020] clarifies its importance for leaky gut etc.
  • Mycotoxin: Its Impact on Gut Health and Microbiota [2018]
  • Impact of mycotoxins on the intestine: are mucus and microbiota new targets? [2017]
  • Effects of Dietary Mycotoxins on Gut Microbiome [2017]
• There are some known impacts on the microbiome of some of the mycotoxins:
  • The effect of experimental fusarium mycotoxicosis on microbiota diversity in porcine ascending colon contents. [2014]”significantly reduced amounts of Clostridium perfringens, Escherichia coli, and Enterobacteriaceae but increased the biodiversity.”
  • Combination of metagenomics and culture-based methods to study the interaction between ochratoxin a and gut microbiota.[2014]  “Bacteroides, Dorea, Escherichia, Oribacterium, Ruminococcus, and Syntrophococcus were decreased and Lactobacillus increased”
  • “increased the relative abundance of cecum Bacteroides and decreased the butyric acid producing bacteria”  Protective effect of curcumin on ochratoxin A-induced liver oxidative injury in duck is mediated by modulating lipid metabolism and the intestinal microbiota.[2020]
  • A longer list of impacts is below
• There is considerable evidence that it may play a significant factor for ME/CFS (and likely many co-morbid conditions) as well as COVID (and Long COVID)
  • Metatranscriptomic analysis revealed Prevotella as a potential biomarker of oropharyngeal microbiomes in SARS-CoV-2 infection [2023]
  • COVID-19–Associated Mold Infection in Critically Ill Patients, Chile [2021] “Centers in Europe, China, and the United States have reported cases of fungal superinfections among patients with severe coronavirus disease (COVID-19).”
  • “Association of concurrence between sick building syndrome and CFS: Epidemic neurasthenia revisited” [1994] “We conclude that CFS is often associated with Sick Building Syndrome”.
  • Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome [2013] “”Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin” 
  • Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients [2022] (chart is below)

There is limited study of the microbiome and mycotoxins. There is an association of mycotoxins and Prevotella copri but in the clinical literature, high levels of Prevotella copri is not reported for ME/CFS – thus we should infer that it impacts a subset only.

Mycotoxin impact on the microbiome

Information here is sparse (and high level)

Oral Sub-Chronic Ochratoxin a Exposure Induces Gut Microbiota Alterations in Mice [2021]. This study found that the the shifts were positive or negative depending on dosages (marked with a * indicating shift seen for low dosages).

Unclassified Bacteroidales	Increases
Bacteroidaceae	Increases
Porphyromonadaceae	Increases
Prevotellaceae	Increases
Rikenellaceae	Increases
S24-7	Increases
Odoribacteraceae	Increases
Unclassified Cyanobacteria	Increases
Deferribacteraceae	Decreases*
Lactobacillaceae	Increases
Streptococcaceae	Major Increase
Unclassified Clostridiales	Decreases
Clostridiaceae	Increases
Dehalobacteriaceae	Increases
Lachnospiraceae	Decreases*
Peptococcaceae	Increases
Ruminococcaceae	Decreases
Mogibacteriaceae	Increases
Erysipelotrichaceae	Decreases
Unclassified Alphaproteobacteria	Decreases
Alcaligenaceae	Decreases
Desulfovibrionaceae	Increases
Enterobacteriaceae	Major Increase
Anaeroplasmataceae	Increases

Prevotella copri Levels Of Concern

A Summary is below — but bacteria do not follow a bell curve. Instead look at the chart below

Values over 0.01% are of concern (IMHO)

Bottom Line

We know that we do not know much about different mycotoxins and their associated fungi. This is made worse because of an absence of standards!

In most cases, if visible mold growth is present, sampling [for mold] is unnecessary. Since no EPA or other federal limits have been set for mold or mold spores, sampling cannot be used to check a building’s compliance with federal mold standards. Surface sampling may be useful to determine if an area has been adequately cleaned or remediated. 

Mold Testing or Sampling – United States Environmental Protection Agency

As you can see from the chart below, ideally some 34,000 species should be tested for. Often people test using a $10 kits (Home Depot) or use an inspector that tests for only a few species. Chart Source

Can we definitively say that high Prevotella copri indicate a fungi issue — No. for some types of fungi that appears true but not for all.

We know that fungi can alter the microbiome but details on the fine print is missing.

Beware of Mycotoxins in Food

Mycotoxins are chemicals — sterilization does not kill the mycotoxins. It will kill the fungi producing the mycotoxins but the mycotoxin will still be there. Some examples:

• Special Issue: Coffee, Fungi, Mycotoxins, and Climate Change. [2023]
• Mycotoxins in milk: Occurrence and evaluation of certain detoxification attempts [2023]
• Filamentous fungi in artisanal cheeses: A problem to be avoided or a market opportunity? [2023]
• Occurrence of Types A and B Trichothecenes in Cereal Products Sold in Romanian Markets [2023]
  “Results indicated trichothecene contamination in 90.08% of our samples, with deoxynivalenol predominating by at least 78% in each examined group. Co-occurrence of three or four trichothecenes were found in 23.85% of our samples. “
• Alimentary Risk of Mycotoxins for Humans and Animals [2021]
  “Memis et al. [79] showed the presence of AFM₁, OTA, ZEN, and DON in human milk.”
  “Their occurrence is favored by factors commonly present in our environment, including humidity. Modified mycotoxins may be a particularly significant risk. However, no legal regulations regarding safe levels in food and feed exist, and risk assessment studies are still ongoing. Mycotoxins show resistance to technological processes and have the ability to accumulate in tissues. “

In short, storage in a humid environment increased mycotoxin risk.

Keep your environment dry!

This usually means dehumidifiers. We have one as part of our heat pump system and smaller units in storage area. We usually set it to 40% humidity or less. We also picked up some Airthings monitors which send us messages when humidity becomes a concern.

Low humidity is also helpful for dealing with heat. The body is able to cool you down faster by sweat.

Image from Best Dehumidifiers for Your Home

We use a unit ($25) like below to keep an eye on each room. One for Three Digital Thermometer Hygrometer

I am newly ill from ME/CFS (4-5 months) and wonder if my results look like a “typical ME/CFS” for you, or Long Covid for that matter.  I am a bit confused and some of the recommendations are contradictory.From Reader. He used Biomesight.com (serves the world, discount code “Micro”)

This will be an interesting analysis — the microbiome evolves over time, so a 20 year ME/CFS and a few months of ME/CFS will have differences. I know of no clinical studies looking at “fresh ME/CFS”. There are studies for “fresh Long COVID”.

Percentages of Percentiles

This tends to have a regular pattern for ME/CFS and Long COVID for most people. Over representation of bacteria in the 0-9% percentile range. This matches his pattern. A healthy person would have all of the bars around 10% – they are not.

Going to the Potential Medical Conditions Detected, there was nothing significant. Prevotella copri is 2% (78%ile) which is borderline for mold issues — it would be good to do inspect the home for that risk. Dr. Jason Hawrelak Recommendations comes in at 99.7%ile with high Methanobrevibacter and low Bifidobacterium being the most severe shifts. Anti inflammatory Bacteria Score is 63.1%ile which is a bit better than most people. So, many medical professionals would tell the patient that I cannot see anything wrong.

Special Studies

Special studies are statistical studies that uses samples uploaded and look at the self-reported symptoms. The analysis is done individually for each lab (needed because of differences in how labs process samples). In this case… we see that COVID Long Hauler is by far the strongest match, almost double the next one.

I did the usual Just Give Me Suggestions and then did the Long Hauler suggestions . This gave five (5) packages of suggestions. I then looked at the antibiotics suggestions, focused on those used with ME/CFS. The top ones are:

• METRONIDAZOLE (ANTIBIOTIC)
• AZITHROMYCIN,(ANTIBIOTIC)S
• CHLOROQUINE DIPHOSPHATE
• DAPSONE (ANTIBIOTIC)

If you have a cooperative MD, I would suggest following the protocol of the Belgium MD, Cecile Jadin: Dr. Jadin’s Current Protocol for ME/CFS.

The list of suggestions to take is actually bigger than usual.

• REMEMBER: There is no need to take all of them, just take what works for you (i.e. no adverse effect and acceptable cost).
• Probiotics should be rotated (change to a different one) every 7 to 14 days. Probiotics often work by producing natural antibiotics. Continuous taking of the same probiotics may result in it not working because of “natural antibiotic resistance”.
• The colors have no meaning except as indicators for category. For example, green is probiotics
• Dosages are those that have been used in clinical studies (for other conditions), and thus deemed safe dosages. Often I have see people taking < 1% of these dosages and wondering why nothing happens.

For example, it you are lactose intolerance, then ignore the lactose suggestion. If not, regular cups of good Belgium Cacao would be a good prescription!

The safe retail probiotics were calculated to be

• symbiopharm/ symbioflo2 – an E.Coli probiotic from Germany
• Filmjölk (SE) / Filmjölk – a Swedish milk drink
• enterogermina – Bacillus Clausii
• SunWavePharma / Spor Sun – Bacillus Clausii

Why are these lists not the same? The latter list are ones that will not shift a single one of the bacteria we are focused on in the wrong direction: NOT A SINGLE BACTERIA. This is an extremely safe conservative suggestion. The top list with probiotics in green often contain probiotics that shifts 30 bacteria in the right direction and 3 in the wrong direction. The odds are that they are very likely to help.

We have a third list of probiotics (to make probiotic suggestions even more confusing), the KEGG suggestions. This looks at what enzymes your microbiome are low in, then sees which probiotics can provide those enzymes. Our goal is to reduce enzymes starvation; this cascades in metabolites — chemicals that the body uses — starvation. The key items from this list are:

• Escherichia coli (symbioflor-2 above or Mutaflor)
• Bacillus subtilis subsp. natto (1/3 of contribution of E.Coli probiotics)
• Bacillus subtilis (1/3 of contribution of E.Coli probiotics)
• Lactobacillus plantarum subsp. plantarum (1/4 of contribution of E.Coli probiotics)

If you have significant brain fog, I would be careful with taking lactobacillus probiotics. Some retail species can increase brain fog.

The Avoids

Frequently “good suggestions for general health” are bad for some conditions. The avoid list of things to avoid is short

Some quick translation: no iron supplements (ferric citrate), beta-glucans usually means no oats, barley or Reishi mushrooms. The names are those used in clinical studies — so they tend to be “unresolved” often in common speech.

Suggested Cycles

After implementing the above suggestions for 6 weeks, do another test and see what has changed.

Questions and Answers

Q: Is it best to take the antibiotics + the protocol you suggested ? Or is it one or the other?

• A: My own choice would be to do both at the same time. If you follow Jadin’s approach, then
  • First week of antibiotics per month — no probiotics at the same time
  • Second week do some of the probiotics (I am inclined towards the E.Coli probiotics but that is based on my personal experience — your mileage may vary)
• Rotate the other supplements over the weeks. I would suggest 10 days and then change to a different set.

Q: And lastly, in the « Avoids », the « vegetarians » suggestion is a little confusing to me. What does it mean?

• Vegetarians mean no animal or fish is being consumed. So, have fish — but some animal proteins are to be reduced: no pork, moderate beef. Duck, chicken and rabbit are fine.

Q: The suggested dosage in the suggestions seems very high. 30g of Vitamin C per day??? Is this correct ?

• The actual dosage should be discussed with your medical professional. The dosages are the highest that have been done in clinical studies and thus assumed to be safe dosages. We have no data on what the threshold for an effective dosage should be. I have seen a few studies where 1000 mg of a substance has minor/no effect while 1100 mg has twice the impact and 1200 mg has four times the effect. For many substances there seem to be a threshold that triggers changes.
  • Usually start at 1/8 of the dosage and double it every second day until there is a response. If very good keep at that dosage. If bad, cut the dosage in half and try a few more days. Give the body time to adapt.

My comment about mold caused him to check his environment carefully…. what he found was out of sight!

Postscript – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I can compute items to take, those computations do not provide solid information on rotations, dosages, etc.

I cannot tell people what they should take or not take. I can inform people items that have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting. Some suggestions may be counterindicated for other medications you are taking and medical conditions.

The answers above describe my logic and thinking and is not intended to give advice to this person or any one. Always review with your knowledgeable medical professional.

Mold and ME/CFS Relationship

“Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin” from Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome [2013]

“Environmental factors – exposure to mold or toxins has been suspected as a trigger for ME/CFS. However, associations of specific environmental factors with ME/CFS have not been established.” [CDC]

Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients [2022]

This is from a reader that I have been corresponding with since 2017 and known from online groups for decades..

Okay, you don’t want the full saga 😀 (joking ) and so I’ll write the first current impressions of a ME/CFS patient since 1998. I am someone who has tried everything; really everything.
First of all, as I had already told you in chat, I use as a criterion of improvement in the disease the increase in cardiovascular tone, which actually happened for a short time as long as I kept a diet that was not exactly ironclad, but very difficult for me: it involved cutting out all refined sugars.

For those interested, I talked about it here : https://www.fable.it/fluorochinoloni-hrv-dieta-e-me-cfs/ (in Italian — use Google translate) . For the first seven days of the diet nothing changed, nothing! After these 7 days suddenly, keeping to this diet , cardiovascular tone started to increase until … well … I kept the rest of the diet but reintroduced sugars (but not alcohol). Then improvement stopped (but maintained existing improvements).

From Reader

Recent significant events are:

• fluoroquinolones toxicity in 2020
• supplements of akkermansia muciniphila one month before last sample  (see below for his experience)

Ancient Test Results

A test result from 23 August 2016 is below. The test show only few bacteria without any ranges of normal valid. We will compare the few items reported with the latest Biomesight test. There was little change over 7 years.

Any persistent Fluoroquinolones artifacts?

I did a behind the UI Meanings? Comparison of what Fluoroquinolones changed with his sample. Although it has been 3 years, I am curious. No impact would have 50-50 agreement. In the result? We have 64 bacteria showing the effect that that Fluoroquinolones would cause, and 43 showing the opposite effect. This results in a P-Value of 0.0423 from chi-square. A P-value below 0.05 is deemed statistically significant in medical studies. So, this is evidence that the impact of Fluoroquinolones is still there after 3 years.

This is an interesting observation — picking the wrong antibiotic may have effects that persists for years.

Comparing to Ancient Test Shown Above

Each lab uses their own methodologies to measurements (See The taxonomy nightmare before Christmas… for why and Comparing Microbiomes from Three Different Providers for actual example). So we cannot determine if the levels have gone up or down.

• Bacteroides caccae is at 15%ile, still low
• Barnesiellaceae is 0%ile, still low
• Parabacteroides distasonis is 12%ile, still low
• Prevotellaceae is 97%ile, still high
• Prevotella is 97%ile, still high
• Prevotella copri is 95%ile, still high
• Prevotella stercorea is 96%ile, still high
• Anaerostipes is 0%ile, still low
• Catenibacterium is 93%ile, still high
• Clostridium is 26%ile, still low
•  Lachnospiraceae is 2%ile, was high
•  Megasphaera is 95%ile, still high
• Mitsuokella was not reported, was high

The microbiome was been relatively stable over 7 years. In fact, the Biomesight test clarify how extreme the values are (which is not clear from the earlier report).

Where do we go from here?

The Percentage of Percentiles pattern shown below is a match for that seen with many ME/CFS or Long COVID microbiome.

Nerdy Explanation: Using percentiles, the data is transformed to an uniform distribution. An unbiased sample (a.k.a. normal or healthy), would have the same number in each 10%ile range. It does not. We have the typical spike in the 0-9%ile range (i.e. too many species and genus that have token representation).

The most important/concerning bacteria identified was Prevotella copri. This bacteria made up 43% of the microbiome!!!! This bacteria is often associated with mycotoxin being present in the environment [2020]. In simple words, Prevotella increases when there is mold in the environment, the chemicals that the mold gives off, feed this bacteria. This usually means examining the living space for mold and fungi, as well as avoiding foods likely to have mold (see WHO for more information). His response to this comment was:

Yes, I live in a north-oriented flat where there is never sun on the walls. Only in a bedroom not used anymore as bedroom I have visible mold (picture attached). I have tried treating with chlorine bleach. In February 2023, I called in a painter. He treated with anti mold solution and thermal painting (which can be dangerous. I wouldn’t lived in that bedroom till the smell went away.
And yes, being in the sun recharge me. I don’t know if it also affects mycotoxins. However in my block / area where I live, we never have less than 60% humidity, but in summer usually we have 70-75% so… humidity is a concern.

From Reader

There are many sites providing suggestions on this issue, a few are: [Aircare Hawaii] and this
Is mold related to humidity?
European and Italian homes are typically built with reinforced concrete frames and brick walls.
Walls and ceiling surfaces are finished with mortar/plaster and water base paint. As water base
paint is not waterproof, plaster finishing tends to absorb and retain humidity. These areas can
become damp or wet as a result of a water leak or condensation of vapors produced by appliances
and normal household activities.

The use of a waterproof paint after cleaning (and running a dehumidifier) in the bedroom is one possible approach. Reader responded (to his delight) that water proof paint was used!

Mold and ME/CFS Relationship

“Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin” from Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome [2013]

“Environmental factors – exposure to mold or toxins has been suspected as a trigger for ME/CFS. However, associations of specific environmental factors with ME/CFS have not been established.” [CDC]

Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients [2022]

This plus other shifts, matches to a host of conditions shown below. Many are co-morbid with ME/CFS.

The Computed Probiotics from KEGG Enzymes had some very high numbers (over 600!). High numbers mean that there count of many enzymes being produced by your microbiome is very low. This is important because processing of food may be disrupted. Some of these are available in probiotics, with the top feasible suggestions being:

• Escherichia coli
• Brevibacillus brevis
• Bacillus subtilis
• Bacillus licheniformis
• Bacillus subtilis subsp. natto
• Clostridium butyricum
  

Two retail probiotics for the Bacillus above are: Energybalance / ColoBiotica 28 Colon Support and microbiome labs/ megasporebiotic. The person is in Europe, so the two E.Coli probiotics: Symbioflor-2 and Mutaflor are available. For others, see Probiotic Mixtures.

I will defer the rest of the suggestions to the PDF, attached below. It is interesting to note that akkermansia muciniphila probiotics is well recommended (see experience below).

In this case, we have good positive reader experience happening before the suggestion was made! It should encourage the reader to trust the other suggestions (after all, “one suggestion worked before he got it!” 🙂 )

I also looked at the MD version which suggested a few antibiotics:

• oxytetracycline dihydrate (antibiotic) – a broad-spectrum tetracycline antibiotic
• thiamphenicol (antibiotic)
• ß-lactam (antibiotic)s (33% of p.copri resistant [2022])

None of these are typically used for ME/CFS (but other tetracyclines are). We have one big target: P.Copri. I am hoping that you have a cooperative MD. I checked around for information on antibiotics which often have little effect on P.Copri, these studies have extensive lists.

• Antibiotic resistance in Prevotella species isolated from patients with cystic fibrosis [2013] – you want runs with R being a zero (0) in Table 1
  • I am inclined to metronidazole, which is often used in treating ME/CFS (also in this 2010 study), and 98% effectiveness reported in this 2019 study.
    

Akkermansia Muciniphila Experience

Another thing Ken, is the sensational discovery this year of Akkermnasia Probiotics (in my case from Metagenics). In my first two days I went from going to the bathroom once a day to going three four times. How many times have we read that a normal bowel transit involves 1 evacuation a day to one every 2-3 days ? No ! The ideal transit is to go to the bathroom about half an hour after eating ! Well, this happened to me while supplementing Akkermansia once a day. And it is only one strain !!! Not only that ! I felt less “Fight or Flight” but more serene, even when I woke up from my night sleep. Even with scabs on my eyes that who knows how many years I haven’t found (how many of us have perpetually dry eyes ?). I stopped the supplementation after a month and am now resuming it.

Why am I writing you this Ken ? To waste your time !!! No, I am writing this to you because I had first read about this Akkermansia three years ago on the label of an Austrian product, Omni Logic Plus, which contains a lot of good stuff (FOS, GOS , etc.) to feed this specific bacteria, Akkermansia . Three years of supplementation every day has not improved anything.
After just a few days of Akkermansia , that is, the strain that that Omni Logic Plus was supposed to feed, did the miracle happen! What do I mean by all this ? That , my thought is that rather than depending on the food, if they are available as supplements, little bacterial strains should be introduced, for a far better effect.

From Reader

Questions:

Q: When the “nutrients” of the supernumerary bacteria are present they grow. If you cut off their nutrients, the effect on microbiota diversity is extremely “reactive” !!! Did this happen when I removed the sugars ?? Do you agree with my reasoning ?

• A: Yes — consider a human population that is well fed (obese even). If you suddenly impose strict rationing on them, their behavior changes greatly (often with criminal actions).

Q: Is it more effective to remove the food that feeds the overrepresented bacteria and simultaneously supplement the underrepresented strains not so much with diet and food, but with probiotics ?
An example of my personal case ? When in the report generated by your site I see among the recommendations clostridium butyricum , which I’ve never tried in my life.

• A: The algorithms effectively does that — identifies suggestions reduced high bacteria while checking that it does not further reduce low bacteria of concern. Also the reverse, suggestions increases low bacteria while checking that it does not further increase high bacteria of concern.. You can try to calculate these manually — but its a massive amount of reading and searching. Microbiome Prescription uses some 1.8 million facts pulled from almost 12,000 studies.

Q: Who knows if it can give me the same benefits as Akkermansia? After years where for weeks on end , I have tried various products. Like everyone else, I have been spending hundreds of Euros. For example:

• probactiol duo ( billions of Saccharomyces boulardii)
• 8.5 billion of a probiotic blend – HOWARU blend (Lactobacillus acidophilus NCFM®, Bifidobacterium lactis Bi-07®, Lactobacillus paracasei Lpc37™, Bifidobacterium lactis Bi-04™)

• A: The purpose of Microbiome Prescription is to compute the most likely ones based on your microbiome and what studies reports the effects of various probiotics are. This means greatly increased odds of positive effects! Much better (and cheaper in the long run) than trying things suggested by influencers or which worked for someone with a very different microbiome.

Your list is very short — 50% is what you recently discovered works!!

For probiotics, do one at a time for 10 days then rotate to another. Why? Their effect is often due to natural antibiotics that they produce. Keeping on them continuously allows “natural antibiotic resistance” to develop.

Postscript – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I can compute items to take, those computations do not provide solid information on rotations, dosages, etc.

I cannot tell people what they should take or not take. I can inform people items that have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting. Some suggestions may be counterindicated for other medications you are taking and medical conditions.

The answers above describe my logic and thinking and is not intended to give advice to this person or any one. Always review with your knowledgeable medical professional.

In my last post, many studies cited proteins being altered.

Fibromyalgia pain may be “microclots” et al

I asked ChatGpt to list the proteins involved. The answer matched my memories (and saves time digging up citations)

Coagulation, also known as blood clotting, is a complex physiological process that involves a series of protein interactions. The main proteins associated with coagulation are part of the clotting cascade, which can be divided into two pathways: the intrinsic pathway and the extrinsic pathway. These pathways eventually converge to activate a common pathway leading to the formation of a stable blood clot. Here are some key proteins involved in these pathways:

Intrinsic Pathway:

1. Factor XII (Hageman Factor): It initiates the intrinsic pathway by becoming activated upon contact with exposed subendothelial surfaces.
2. Factor XI (Plasma Thromboplastin Antecedent): Activated by factor XIIa, it then activates factor IX.
3. Factor IX (Christmas Factor): Activated by factor XIa, it forms a complex with factor VIIIa and calcium ions to activate factor X.
4. Factor VIII (Antihemophilic Factor A): This protein, along with von Willebrand factor, is involved in stabilizing factor IX and preventing its premature degradation.
5. Factor X (Stuart-Prower Factor): Activated by the factor IXa-factor VIIIa complex, it is a critical point where the intrinsic and extrinsic pathways converge.

Extrinsic Pathway:

1. Tissue Factor (Factor III): Released from damaged tissues, it combines with activated factor VII to initiate the extrinsic pathway.
2. Factor VII (Proconvertin): Activated by tissue factor, it forms a complex with tissue factor to activate factor X.

Common Pathway:

1. Factor X (Stuart-Prower Factor): Activated by both intrinsic and extrinsic pathways, it forms a complex with factor V to convert prothrombin (Factor II) to thrombin.
2. Factor V (Labile Factor): Forms a complex with factor X to accelerate the conversion of prothrombin to thrombin.
3. Thrombin (Factor IIa): Generated from prothrombin, thrombin is a central enzyme in coagulation. It converts fibrinogen to fibrin, activates factor XIII, and also plays a role in platelet activation.
4. Fibrinogen (Factor I): Thrombin cleaves fibrinogen to form fibrin monomers, which then polymerize to create a fibrin mesh that stabilizes the blood clot.
5. Factor XIII (Fibrin-Stabilizing Factor): Activated by thrombin, it crosslinks fibrin strands, contributing to the stability of the clot.

This cascade of protein interactions ultimately leads to the formation of a stable fibrin clot that helps prevent excessive bleeding at the site of injury. It’s important to note that coagulation is a tightly regulated process, and any imbalance can lead to bleeding disorders (if clotting is impaired) or thrombotic disorders (if clotting is excessive).

From Coagulation Cascade

For FM, ME/CFS and Long COVID — different enzymes!

The amount of each protein is often determined by a person’s DNA. For example, I have a Prothrombin G20210A defect A.K.A. Factor II mutation since that is what it impacts. A person may have multiple DNA coagulation defects. The typical impact of a defect is to create a bottleneck in the normal process resulting in micro-clots, sticky blood and other manifestations. For myself, there are several documented fibrinolytic substances (dissolvers of fibrin) which I use periodically. It works for my defect (it may not for other defects).

The usual problems are:

• Getting DNA testing, many labs and MDs will only test some items: “When testing is indicated, we only screen for the G20210A variant and not for the other rare F2 variants listed above.”[src]
• The best general treatment is low molecular weight heparin (Lovenox is one brand) – why, because it usually has all of the proteins in it — thus an absence is compensated. The downside is that if you have a surplus of one protein it may make things worse — i.e. bleeding risk.

A question was asked on Facebook which I recall some studies report hypo-perfusion (too low oxygen levels) at the pain points. This aspect was first suggested/found by David Berg back in 1999 [see this post for more details]. The old studies:

• Chronic fatigue syndrome and/or fibromyalgia as a variation of antiphospholipid antibody syndrome: an explanatory model and approach to laboratory diagnosis, Dave Berg, 1999.
• The pain of fibromyalgia syndrome is due to muscle hypoperfusion induced by regional vasomotor dysregulation [2007]

I was delighted to see many more studies.

Some terms that are connected to coagulation: fibrinogen (Major component of clots). Cerebral blood flow is the amount of oxygen reaching the brain, with coagulation this decreases [the brain becomes starved for oxygen].Prothrombotic is another name for Hypercoagulable state (A.K.A. Thick Blood) 

 Elevated platelet and RBC counts, PDW values, and fibrinogen levels as well as decreased prothrombin time are all indicative of a prothrombotic state in FM patients, which may be enhanced by an increased inflammatory tone. 

Are Patients With Fibromyalgia in a Prothrombotic State? [2019]

• ” Clear significant differences between FM … FM had associations with specific plasma proteins involved in blood coagulation, metabolic, inflammation and immunity processes.” [2020]
• “we noted several proteins involved in coagulation and inflammation pathways with distinct expression patterns in patients with FM.” [2020]
• “This study suggests that different plasma protein patterns are associated with different pain intensity and psychological distress in CWP. Proteins belonging to the coagulation cascade and immunity processes showed strong associations to each clinical outcome” [2018]
• “The interplay of the complement and coagulation cascades contributes to the inflammatory process, while the activation of Liver-X Receptor/Retinoid-X Receptor and Farnesoid-X Receptor/Retinoid-X Receptor could attempt to alleviate it. Finally, we have identified two proteins, haptoglobin and fibrinogen, as potential biomarker-candidates of FM for future studies.” [2018]
• “Significant correlations were found between thalamic Cerebral blood flow [rCBF] values and pain belief values.” [2011]
• “These results show that brain perfusion abnormalities in patients with fibromyalgia are correlated with the clinical severity of the disease.” [2008]
• “in hyperalgesic FM patients, we found significant hyperperfusion in regions of the brain known to be involved in the sensory dimension of pain processing and significant hypoperfusion in areas assumed to be associated with the affective-attentional dimension. ” [2006]
• Decreased muscle blood flow in fibromyalgia patients during standardised muscle exercise: a contrast media enhanced colour Doppler study [2006] “that muscle ischemia(an inadequate blood supply to an organ or part of the body) can contribute to pain in FM,”
• Intramuscular hypoperfusion, adrenergic receptors, and chronic muscle pain [2002] “a prominent and consistent feature for regional myofascial pain and to a lesser degree for fibromyalgia was intramuscular hypoperfusion”
• Tissue oxygen measurement and 31P magnetic resonance spectroscopy in patients with muscle tension and fibromyalgia [1997] – “hypoxia” — low oxygen levels

Bottom Line

This area tends to fall into a medical no-physician land. Clinical MDs are rarely familiar with coagulation and if pressed, will pass patients to what they deem to be an appropriate specialist – a hematologist. A hematologist will ask “show me the strokes, the venous clots etc” and then excuse himself from involvement. The issue is that of low grade, clinically significant, low level coagulation often known as “micro-clots” in recent Long COVID literature.

Coagulation disorders are complex. Some have well established treatments, some do not.

Some additional notes:

Recap on Coagulation Complexities

Coagulation: Thick Blood Supplements for CFS and Long COVID

Thick Blood, Clots dimension of CFS etc

Coagulation Issues – Testing and Literature