CFS Patient after COVID using the Special Studies Results

Foreword – 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 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.

Back Story

  • Male, 39 years old.
  • Was on antibiotics for 4 years between ages of 16 and 20 for adolescent acne.
  • Severe Onset 4 years ago (around June 2018) after a succession of stressful events.

Symptoms include:

  • Swelling on lymph nodes in throat
  • Cramping
  • Ataxia, unsteady gait, brain fog, trouble thinking, speaking, peripheral neuropathy (tingling in left thumb and index finger)
  • Dizziness
  • Headaches
  • Visual impairment / visual processing impairment
  • Extreme Fatigue / drowsiness
  • Rash on neck and groin
  • Facial spasms
  • Postural hypotension, blacked out many times when standing
  • Have suffered from sinusitis from around 21 years old (seen small improvement lately after taking polyphenols daily)
  • Suffered from anxiety and bouts of depression from around age 16

Since 2018 all forms of dairy have exacerbated my symptoms. Previously I didn’t notice any issue with dairy but in hindsight it might have been one of the triggers for my sinusitis. Having removed it from my diet my symptoms are much improved (less fatigue, more energy), although I still suffer from the cognitive impairment this has been improved by circa 25%.

See below for some more information

High Level Overview

Potential Medical Conditions Detected page found some apparent matches:

  • Metabolic Syndrome
  • Gastroesophageal reflux disease (Gerd) including Barrett’s esophagus
  • Mood Disorders
  • Insomnia

Item like hypertension (High Blood Pressure are define miss — since POTS is typical with ME/CFS.

In terms of bacteria deemed unhealthy

Dr. Jason Hawrelak Recommendations came up at the 89%ile, most were just outside of his ranges.

Looking at distributions, we see a large number of bacteria with just a token presence (0-9%ile)

Looking at Special Studies, we find good matches for several conditions.

Interpreting the updated table shown below can get a little complicated because we are looking at rarely seen bacteria that occur at low levels usually. This can be impacted by the quality of the reads — a low read count will have less of these detected (i.e. both rare and low counts). Getting over 50% is significant, if the top ones are close to each other, use the top 6 or until there is a gap in the numbers.

I contacted this person and asked about some of the above and got this response:

  • I have sleep problems. I am a very light sleeper and get up several times in the night
  • There is a history of bowel cancer in my family. 
  • I have had COVID at least twice, possibly three times in the last 2 years. 
  • my symptoms always flare together. The sinusitis, rashes, POTS, cognitive impairment, aches and pains and fatigue as well as swollen glands. Not sure if that is significant or a regular hallmark. 
  • With alcohol it can cause a flare in my sinusitis. 
  •  a SIBO test in December 2020 that the practitioner said was positive
  • My symptoms saw the biggest improvement after giving up dairy,
Update from person

This results in my doing each of the double matches (i.e. bacteria matching diagnosis) and generating a consensus report. Conerning Long COVID, he wrote “Not sure if I imagined it or a coincidence but my symptoms felt like they improved marginally after it.”

The Consensus Results

I should point out that my preference is shifting to use the a consensus report based on the Special Studies when the results are from or through BiomeSight. The key for the best results are the best identification of the bacteria that has a statistical role (IMHO). It was interesting to note that two different E.Coli probiotics are at the top (which we also get from KEGG Gene data). Choline deficiency means to reduce choline intake.

Top Top To-Take List

Reducing Choline means reducing foods such as those listed below

US National Institute of Health

On the other end (to avoid) are some vitamins that are often suggested for ME/CFS: Vitamin B-12 and Vitamin-B3 (in fact all B-Vitamins are negative!). This is contrary to usual logic because low Vitamin-B levels are common with ME/CFS which causes me to do a rethink. Is the reason that it is low because it is greedily consumed by bacteria causing the problem? If this is the case, then having low Vitamin Bs levels AND avoiding Vitamin Bs make sense.

Probiotics Suggested based on Clinical Studies

KEGG Computed Probiotics

We now take a totally different method of picking probiotics — from the genes in your bacteria and the genes in the probiotics. Above the choice was based on what studies reported that probiotics shifted bacteria in clinical studies. We see E.Coli near the top, the other odd sounding ones are found in Prescript Assist and Equilibrium cited above. In other words, both paths lead to the same probiotics.

Generated from the bacteria in the sample and using KEGG derived data

Bottom Line

What struck me about this analysis is that the picking of bacteria was very simple — just pick the special studies that have high matches and which is reported by the person. The second aspect is that using the data from Kyoto Encyclopedia of Genes and Genomes resulted in a tight agreement on probiotics from two very different ways of selecting probiotics. This gives me a very warm feeling about the suggestions — genomics and studies are in agreement with selecting bacteria using special studies.

Important Note: I did not do suggestions for the two high bacteria cited at the top: Haemophilus parainfluenzae and Prevotella copri. At the moment I speculate they are side-effects and the above will naturally reduce them without needing explicit action. I did run these two bacteria by hand picking with the following being reasonable candidates to reduce them

  • peppermint (spice, oil)
  • thyme (thymol, thyme oil)
  • wormwood(artemisia)
  • cinnamon (oil. spice)

If you wish to take explicit action, I would take the above only for 2 weeks and then pulse them every 2 months.

I should note that there was universal agreement on the following actions:

  • low protein diet (agrees with low choline diet above)
  • bifidobacterium bifidum (probiotics)
  • xylitol (i.e. xylitol gum is an easy way of getting it)
  • chrysanthemum morifolium (a.k.a. Ju Hua)

With no disagreement over most of the top recommendations between the consensus report and the “bacteria hit list” suggestions.

User Feedback

“The foods to avoid are all foods that I eat regularly so it’s great to have clarity on the need to avoid these.” -interesting observation, he is in a no-progress scenario, his regular diet may be contributing to no progress!

“Regarding the B vitamins, another symptom I have is lack of facial hair that is certainly not genetic as every male on either side of my family has strong facial hair. I am wondering if that is an outward sign of biotin consumption from bacteria? I have been taking high dose biotin recently. This might also explain the brain fog via bacterial consumption of niacin.” – this seems to agree with my speculation about the existence of some greedy consumers of B-vitamins being part of the problem.

“Am I right to assume that a plant based diet and avoiding the foods listed should starve out the B vitamin consuming bacteria and help increase those that I am low in” This is a reasonable assumption and one that I would make. I would suggest a minimum time doing that of 4-6 weeks.

Special Studies: SIBO from multiple different approaches!

This is a common symptom for many people. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does. We are not being specific about the type of constipation. The numbers are less than desired. If you have SIBO and a sample processed thru biomesight (if you have OmbreLab, see how to do this . 📹Video on Transferring Data from Ombre/Thryve to Biomesight ) and then add SIBO as a symptoms. The online data is recomputed once a month so it will improve identification and suggestions.

The second approach is to look at where bacteria identified as statistically significant agrees with KEGG data on Methane, Hydrogen and Hydrogen Sulfide – what is measured in breath tests.

Small intestine aspirate and fluid culture. This is currently the gold standard test for bacterial overgrowth. To obtain the fluid sample, doctors pass a long, flexible tube (endoscope) down your throat and through your upper digestive tract to your small intestine. A sample of intestinal fluid is withdrawn and then tested in a laboratory for the growth of bacteria.

Small intestinal bacterial overgrowth (SIBO) – Mayo Clinic

IMHO, the sample should go thru shotgun processing and not culturing (growth of bacteria)

“Patients with functional dyspepsia also were found to have a greater relative abundance of Streptococcus and decreases in the relative abundance of other genera such as Prevotella, Veillonella, and Actinomyces compared with control subjects, suggesting that their symptoms may be related to alterations of their microbiome at this site…. 16S ribosomal RNA (rRNA) sequencing revealed that SIBO subjects had 4-fold significantly higher relative abundance of Proteobacteria and 1.6-fold significantly lower Firmicutes than non-SIBO subjects. Furthermore, altered Proteobacterial profiles were found that correlated with symptom severity. ”

Current and Future Approaches for Diagnosing Small Intestinal Dysbiosis in Patients With Symptoms of Functional Dyspepsia [2022]

Reservation of SIBO as a Condition

I will be upfront — my motto is Ostende mihi testimonium – Show me the evidence. I do not dispute getting results from Breath Tests – but reading the latest literature [see 2022], it is likely that most of the breath tests are incorrectly done. This is especially true give the type of advice that I have seen on social media compared to the best literature (see above link). SIBO is associated with so many other conditions that I view it as a shared symptom, such as head ache or constipation. Many clinical studies are done in reference to SIBO in the context of this or that condition. This implies that researchers are seeing very different subsets in what is called SIBO. Just with the three existing breath tests, we see 3! i.e. 6 potential subtypes of SIBO – each with different bacteria involved and thus different treatment plan being likely.

In preparing this study, I attempted to disprove my gut feeling but looking for what should be there and could not find it. See below.

Study Populations:

Small intestinal bacterial overgrowth (SIBO)118635
  • Bacteria Detected with z-score > 2.6: found 205 items, highest value was 6.5
  • Enzymes Detected with z-score > 2.6: found 335 items, highest value was 7.9
  • Compound Detected with z-score > 2.6: found No items

Interesting Significant Bacteria

All bacteria was found to be low. This may suggests that bacteria that would consume Methane, Hydrogen and Hydrogen Sulfide may be deficient.

BacteriaReference MeanStudyZ-Score
Pectinatus cerevisiiphilus (species)197936.5
Alkaliphilus (genus)346312396.1
Pectinatus (genus)2011016
Alkaliphilus crotonatoxidans (species)342412355.9
Eubacteriales Family XIII. Incertae Sedis (family)4411575.7
Streptococcus fryi (species)128525.6
Thermoanaerobacter (genus)60255.6
Sedimentibacter (genus)13974605.5
Tissierellia incertae sedis (norank)14024645.5
Legionellales (order)80415.2
Legionellaceae (family)80415.2
Legionella (genus)80415.2
Mogibacterium (genus)4401765
Adlercreutzia (genus)3911705

Interesting Enzymes

As with bacteria, all of the enzymes found significant were too low. We have a lot of them!

EnzymeReference MeanStudy MeanZ-Score
propanoate:CoA ligase (AMP-forming) (
all-trans-zeta-carotene:acceptor oxidoreductase (
15-cis-phytoene:acceptor oxidoreductase (neurosporene-forming) (
15-cis-phytoene:acceptor oxidoreductase (zeta-carotene-forming) (
15-cis-phytoene:acceptor oxidoreductase (lycopene-forming) (
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (
catechol:oxygen 2,3-oxidoreductase (ring-opening) (
5-aminopentanoate:2-oxoglutarate aminotransferase (
(S)-3-amino-2-methylpropanoate:2-oxoglutarate aminotransferase (
(S)-2-hydroxyglutarate:quinone oxidoreductase (
L-carnitinyl-CoA hydro-lyase [(E)-4-(trimethylammonio)but-2-enoyl-CoA-forming] (
glutarate, 2-oxoglutarate:oxygen oxidoreductase ((S)-2-hydroxyglutarate-forming) (
biuret amidohydrolase (
L-carnitine,NAD(P)H:oxygen oxidoreductase (trimethylamine-forming) (
medium-chain acyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (
succinyl-CoA:3-oxo-acid CoA-transferase (
n/a (
(2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate hydro-lyase [(Z)-but-2-ene-1,2,3-tricarboxylate-forming] (
RNA-3′-phosphate:RNA ligase (cyclizing, AMP-forming) (
D-glucose:NAD(P)+ 1-oxidoreductase (
n/a (
(2R)-2-O-phospho-3-sulfolactate hydrogen-sulfite-lyase (phosphoenolpyruvate-forming) (
CDP-ribitol:4-O-di[(2R)-1-glycerophospho]-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol ribitolphosphotransferase (
CDP-ribitol:4-O-[1-D-ribitylphospho-(2R)-1-glycerophospho]-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol ribitolphosphotransferase (
UDP-N-acetyl-alpha-D-glucosamine:lipopolysaccharide N-acetyl-D-glucosaminyltransferase (
D-galactaro-1,4-lactone lyase (ring-opening) (
hydrogen-sulfide:flavocytochrome c oxidoreductase (
3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming) (
[SoxY protein]-S-sulfosulfanyl-L-cysteine sulfohydrolase (
(R)-lactate hydro-lyase (
CTP:5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid cytidylyltransferase (
sulfite:oxygen oxidoreductase (
L-kynurenine hydrolase (
glutaryl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (decarboxylating) (
L-carnitine:CoA ligase (AMP-forming) (
(1E,3E)-4-hydroxybuta-1,3-diene-1,2,4-tricarboxylate 1,2-hydro-lyase (2-hydroxy-4-oxobutane-1,2,4-tricarboxylate-forming) (
alkane,reduced-rubredoxin:oxygen 1-oxidoreductase (
glutaredoxin:hydroperoxide oxidoreductase (
n/a (
isoquinoline:acceptor 1-oxidoreductase (hydroxylating) (
sn-glycerol-3-phosphate:oxygen 2-oxidoreductase (
reduced coenzyme F420:NADP+ oxidoreductase (
4-fumarylacetoacetate fumarylhydrolase (
[sulfatase]-L-cysteine:oxygen oxidoreductase (3-oxo-L-alanine-forming) (
S-methyl-5′-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase (
gamma-butyrobetainyl-CoA:electron-transfer flavoprotein 2,3-oxidoreductase (
(2->6)-beta-D-fructan fructanohydrolase (
(S)-lactate:oxygen 2-oxidoreductase (
(E)-4-(trimethylammonio)but-2-enoyl-CoA:L-carnitine CoA-transferase (
benzoyl-CoA,NADPH:oxygen oxidoreductase (2,3-epoxydizing) (
(S)-mandelate:acceptor 2-oxidoreductase (
5-dehydro-4-deoxy-D-glucarate hydro-lyase (decarboxylating; 2,5-dioxopentanoate-forming) (
2,5-dioxopentanoate:NADP+ 5-oxidoreductase (
ferulate:CoA ligase (ATP-hydrolysing) (
homogentisate:oxygen 1,2-oxidoreductase (ring-opening) (
ADP-glucose:D-glycerate 2-alpha-D-glucosyltransferase (
N,N-dimethylaniline,NADPH:oxygen oxidoreductase (N-oxide-forming) (
ATP:[protein]-N6-D-ribulosyl-L-lysine 3-phosphotransferase (

Significant Bacteria and KEGG modelling

To me, this is where the exploration could get interesting.

The following are consumers of these three compound according to KEGG and are statistically significant in our study, Those marked with * also produces some of these compounds. Whether a bacteria is producing or consuming may depend on what is in the microbiome environment (i.e. enzyme quantity).

  • Adlercreutzia equolifaciens *
  • Butyrivibrio proteoclasticus *
  • Corynebacterium aurimucosum *
  • Emticicia oligotrophica *
  • Escherichia albertii *
  • Escherichia coli *
  • Haemophilus parahaemolyticus *
  • Phascolarctobacterium faecium *
  • Phocaeicola salanitronis *
  • Pseudobutyrivibrio xylanivorans
  • Ruminococcus albus *
  • Streptococcus anginosus
  • Streptococcus equinus
  • Streptococcus oralis (A.K.A. Streptococcus dentisani)
  • Streptococcus vestibularis
  • Turicibacter sanguinis

My perspective is that the consumption (and production) of Methane, Hydrogen and Hydrogen Sulfide is dependent on the availability of enzymes and chemicals produced by other bacteria. Those are not measured in testing — only those three easy to test by last millennium lab tests.

Of the items above, two are potentially available as retail probiotics now, or soon:

Concerning the enzymes listed above, I will leave it to the reader to see where they occur in the following example of a KEGG metabolism diagram.

Methane Metabolism Map

I checked PubMed if there were any studies that used KEGG data for SIBO, there was just one: Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy [2022] – “KEGG pathway analysis revealed that differential metabolites were mainly involved in bile secretion, cholesterol metabolism, and other pathways”

Association of Differential Metabolites With Small Intestinal Microflora and Maternal Outcomes in Subclinical Hypothyroidism During Pregnancy [2022]

What I find really irritating is that some of the bacteria inferred to cause SIBO lacks the genetic/genes/enzymes to produce Methane, Hydrogen or Hydrogen Sulfide. My sole comment is last millennium medical belief versus current millennium medical fact.

Bottom Line

SIBO is difficult to treat. I suspect one of the cause is going with a simplistic naïve view of this condition: It is caused by having too many producers of Methane, Hydrogen and Hydrogen Sulfide. In this study, we found the opposite — it is an absence of consumers of Methane, Hydrogen and Hydrogen Sulfide. Furthermore, the existing consumers may be inhibited in this function by the absence of enzymes needed to consume. This data is coming from downstream, so it may not apply apply fully to the small intestine – however the chemicals and enzymes flowing from the small intestine would impact a stool sample.

If the naïve view was correct, the specific bacteria would have been identified decades ago and SIBO would be resolved by a round of antibiotics targeted at them. That is not people’s experience dealing with SIBO.

The bottom citation is long and well worth reading. It covers issues well with SIBO testing.

Coincident with advances in medical science, diagnostic testing evolved from small bowel culture to breath tests and on to next-generation, culture-independent microbial analytics. The advent and ready availability of breath tests generated a dramatic expansion in both the rate of diagnosis of SIBO and the range of associated gastrointestinal and nongastrointestinal clinical scenarios. However, issues with the specificity of these same breath tests have clouded their interpretation and aroused some skepticism regarding the role of SIBO in this expanded clinical repertoire.

Small Intestinal Bacterial Overgrowth-Pathophysiology and Its Implications for Definition and Management [2022]

Measurement of breath hydrogen (H2) and methane (CH4) excretion after ingestion of test‐carbohydrates is used for different diagnostic purposes. There is a lack of standardization among centers performing these tests and this, together with recent technical developments and evidence from clinical studies, highlight the need for a European guideline.

… SIBO has been associated with multiple conditions including IBS, rosacea, hepatic encephalopathy, obesity, gastroparesis, Parkinson’s disease, fibromyalgia, chronic pancreatitis, end‐stage renal disease, and inflammatory bowel diseases.

H2BT has become the most used test for SIBO in clinical practice; however, this is largely due to its ease of use, non‐invasive character and low cost and not based on evidence from clinical trials.

European guideline on indications, performance, and clinical impact of hydrogen and methane breath tests in adult and pediatric patients: European Association for Gastroenterology, Endoscopy and Nutrition, European Society of Neurogastroenterology and Motility, and European Society for Paediatric Gastroenterology Hepatology and Nutrition consensus [2022]

In short, I do not know what causes the breath test results — there is an abundance of speculation, often held to as fact. There is a absence of solid evidence. What I do know is that bacteria moves up and down in the body – think of the analogy of salmon which moves upstream against strong currents. We see strong statistical shifts in stool samples as a whole, this is evidence that hints that correction may have as a side effect, relief of SIBO.

Microclots and Microbiome: Interaction

The recent news of microclots with Long COVID with researchers looking for the same issue with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) caused me to do this summary of my understanding.

Some literature:

And in the ME/CFS world

My response was simple – “Old news, but the new details is interesting“. The reason it is old, is the research from Hemex Labs and David Berg from back in the 1990’s ( Chronic fatigue syndrome and/or fibromyalgia as a variation of antiphospholipid antibody syndrome: an explanatory model and approach to laboratory diagnosis [1999]).

I’ve just realized that since I started working on my ME and working on my microbiome hypoperfusion symptoms are much worse, but they come and go which I haven’t got a handle on.  I often call it brain fog or mild brain fog.  But it manifests as memory loss, difficulty retrieving information, I’ve just been out to the supermarket and I forgot a series of things I wanted to purchase for example, which means I’ll have to go out again and by that point it would be my third trip!

It’s impossible to get a SPECT scan with correct analysis in the UK sadly, but I am more convinced now after reading your blog that hypo perfusion for me is getting worse, hence my dementia like symptoms!  Memory are often wispy or very faint as well from the last few years.

Anyway are you saying here that you recovered fully by adjusting your microbiome?  Or did you do or take anything else to get you there as well.

An email

A Model on Microclots and Microbiome

My first remission from Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) under treatment occur with two “unrelated” treatments being done concurrently. Each treatment had a 80+% success rate reported in conference papers at the time.

  • Treating Hypercoagulation. My MD worked directly with Hemex labs resulting in Heparin being prescribed. Additionally, I hosted some town halls with David Berg and talked with him at conferences. My specific coagulation issue responded well to piracetam and to a lesser extent, turmeric.
  • Treating an Occult Infection. This was doing the protocol for occult rickettsia developed by the Pasteur Institute for Tropical Medicine and applied successfully to people with ME/CFS by Dr. Cecile Jadin (a surgeon in South Africa — her father worked at the Institute which is why she knew of the protocol).
    • “Occult Infection” was likely the persistence of the microbiome associated with the infection (Rickettsia) and not the actual infection.

Later, some ME/CFS specialists connected the dots — the infection (whatever it was) was triggering the coagulation — hence a two prong approach was needed.

Every time that I have had a flare of ME/CFS, I have done both. Typically without any prescription drugs (but if these do not work, it is back to a friendly MD asking for specific things). The items are:

  • Coagulation: Piracetam (#1 preference), Turmeric, Serrapetase, Lumbrokinease, Nattokinease
  • Infections: Triphala, Olive Leaf, Wormwood often with potenators such as bromelain (which allows them to get thru fibrin deposits).

Updated for 2022

It appears that we may have a feedback loop happening.

  • The coagulation results in low oxygen being delivered to the body. We know that fibromyalgia pain points are associated with hypo perfusion (low oxygen) of the tissue there. Pain is produced by chemical release. It is probable that a host of other chemical signals are sent to the body in an attempt to correct this issue.
  • The chemical signals moves across the body, especially to the guts. These chemical signals to the wrong microbiome results in bacteria increasing what triggers coagulation and vascular constriction.
  • The cycle repeats — for some, it quiets down, for some, it becomes uncontrolled feedback (and they keep getting worse) and for others, they are locked into a reasonable stable cycle (the living death).

Treatment Implications

With the above model, we have two goals that needs to be addressed at the same time:

  • Increasing oxygen flow to the entire body. Typically this means one or more of the following:
    • Anti-coagulants – best general one is low-dosage heparin. It’s cheap and if taken sublingual, no injections are needed. For my own coagulation mutation, piracetam works as well.
    • Fibrinolytics: Typically bromelain, nattokinease, serrapetase, lumbrokinese. Fibrin deposits can prevent the passage of oxygen to the tissue.
    • Vascular dilators: My favorite is flushing niacin. I take 400 mg twice a day as a prophylactic. If I get a flush, I know it is warranted. There are others.
    • Anti-inflammatory: Having blood vessels inflamed restricts oxygen delivery. There are many choices here, likely good to rotate thru several and note any that causes significant improvement.
    • Hyperbaric Oxygen Chambers: A short term assist but does not address the cause
  • Encouraging the microbiome to reform.

None of the above is likely to occur fast. In my case, I did 8 days of the highest dosage of aspirin suggested on the bottle and ended up running up and down the walls. It persuaded my MD to do testing via Hemex labs. Taking aspirin longer is not viable. In general, it is a slow long trek. I do like to do microbiome testing periodically because it gives an objective measure of progress (i.e. more normalization of the microbiome). This has been seen with several post of people with ME/CFS who has started doing suggestions with periodic retests.

Car Analogy

The human body is fare more complex than a car, but the car analogy is a good starting point. The car is running “rough” – some possible causes:

  • Fibrinolytics – clogged oil or gas filter
  • Anti-coagulants – fuel stabilizer, many fuels will become jelly like or deteriorate if left a long time
  • Vascular dilators – fuel or coolant lines, if pinched, the engine may not work well
  • Anti-inflammatory – fuel or coolant lines have garbage in them or deteriorating or wrong size
  • Feedback loop: Engine timing is off. Sparkplugs are firing too late or early
  • Dashboard Dials: Sending the wrong signals (i.e. fuel gauge is not working), high RPM because you forgot to change gears, etc

Quick Lesson on Coagulation

Often there can be a weakness (DNA/SNP mutation) that makes one part less efficient. Typically, this may not cause any issue –but with the wrong sets of chemical signals, it can either overproduce items “upstream” or inhibit one step.

The diagram shows the cascade, all it takes is one weak link or a different link getting stuck on high.


Bottom Line

The biggest challenge is treating all of the factors concurrently. Many MDs will opt for a “let us try just one thing at a time”. You cannot isolate the parts and deal with just one — the signaling chemicals will keep flowing across the entire body. This approach rarely works when there are multiple feedback loops occurring. Personally, I use the flushing niacin as a feedback loop damping mechanism. If I have a cold, flu or other issues, I will add in other stuff to try to keep the loop from getting re-established.

Special Studies: General ME/CFS

There are 3 choices for Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) to annotate samples.

  • ME/CFS (i.e. not sure if they have or do not have IBS)
  • ME/CFS with IBS
  • ME/CFS without IBS

We are going to combine those together to look for commonality and if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does, but the degree of association (z-scores) are lower than with ME/CFS with/without IBS. This is expected because mixing conditions typically results in a more divergent microbiome population thus the scope of treatment increases.

For those with 16s Samples

REMEMBER: When you upload your 16s samples to add symptoms! It is how we get these special studies that appear to get a lot more results than published studies.

Study Populations:

Chronic Fatigue Syndrome (CFS/ME)1018159
  • Bacteria Detected with z-score > 2.6: found 174 items, highest value was 6.6
  • Enzymes Detected with z-score > 2.6: found 148 items, highest value was 4.5
  • Compound Detected with z-score > 2.6: found 6 items, highest value was 3.1

The highest z-scores above are lower than other symptoms despite bigger sample size. It was interesting to see that some compounds reached significance (likely due to the much larger sample size)

Interesting Significant Bacteria

All bacteria found significant had too low levels. Many Bifidobacterium species are significant as well as low Prevotella copri which appears on special studies on many co-morbid symptoms. The good news, is that there is work ongoing to produce a prevotella copri probiotic.

We do see a few overgrowth These are seen only in some subsets.

  • Cetobacterium (genus)
  • Bacteroides rodentium (species)
  • Fusobacteriaceae (family)
  • Anaerolineae (class)
  • Fusobacteria (phylum)
BacteriaReference MeanStudyZ-Score
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)330616.6
Bifidobacterium cuniculi (species)83265.7
Tenacibaculum (genus)28105.5
Shuttleworthia (genus)2961005.3
Bifidobacterium gallicum (species)39469375.3
Prevotella copri (species)69586219055.2
Sporolactobacillus (genus)181645.2
Sporolactobacillus putidus (species)181645.2
Sporolactobacillaceae (family)179645.1
Veillonella (genus)411724095
Nitrosomonadales (order)61364.7
Clostridium chartatabidum (species)319704.6

Interesting Enzymes

Most enzymes found significant had too low levels. A few were higher, the tip ones were connected to ferredoxin. This implies over reduction of the enzyme NADP+ reductase. I suspect that this may impact hemoglobin (what carries oxygen in the blood), and reduces it’s ability to carry oxygen — thus producing fatigue.

  • CoB,CoM,ferredoxin:H2 oxidoreductase (
  • CoB,CoM:ferredoxin oxidoreductase (
  • CoB,CoM,ferredoxin:coenzyme F420 oxidoreductase (
  • coenzyme B,coenzyme M,ferredoxin:formate oxidoreductase (
EnzymeReference MeanStudy MeanZ-Score
6-amino-6-deoxyfutalosine deaminase (
chorismate hydro-lyase (3-[(1-carboxyvinyl)oxy]benzoate-forming) (
S-adenosyl-L-methionine:3-[(1-carboxyvinyl)-oxy]benzoate adenosyltransferase (HCO3–hydrolysing, 6-amino-6-deoxyfutalosine-forming) (
dehypoxanthine futalosine:S-adenosyl-L-methionine oxidoreductase (cyclizing) (
hydrogen-sulfide:flavocytochrome c oxidoreductase (
[SoxY protein]-S-sulfosulfanyl-L-cysteine sulfohydrolase (
CTP:5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid cytidylyltransferase (

Interesting Compounds

Compounds are computed from the amount produced – amount consumed by the bacteria (hence we can get negative numbers).

NamesReference MeanStudy MeanZ-Score
Glutarate (C00489)20968703.1
Prokaryotic ubiquitin-like protein (C21177)22452.9
[L-Glutamate:ammonia ligase (ADP-forming)] (C01281)527912.7
Adenylyl-[L-glutamate:ammonia ligase (ADP-forming)] (C01299)527912.7
4-Amino-5-aminomethyl-2-methylpyrimidine (C20267)-23607-16191-2.7
D-Mannitol 1-phosphate (C00644)18249114782.6

This agrees with the research (suggesting that this model is working)

As well as social media

Bottom Line

It is unclear if glutamine or glutamate supplement will immediately help (See Role of dietary modification in alleviating chronic fatigue syndrome symptoms: a systematic review, [2017]). In my old blog post on Glutamine (also in 2017) I wrote “The available evidence suggests that glutamine supplementation may worsen the shift of bacteria seen in CFS/FM/IBS”.

In terms of the model, glutamate is likely to help normalize the gut overtime. I would still hesitate with glutamine.

In terms of probiotics, Bifidobacterium probiotics and likely Clostridium butyricum (miyarisan) are the best candidates based on the shortage of bacteria. Only one Lactobacillus probiotic should be considered:  Lactobacillus Bulgaricus, but it is a very weak suggestion.

Remember, the purpose of these studies is to identify items to be investigated (ideally by others). The data for microbiome manipulation is incorporated in the AI Suggestions algorithm on Microbiome Prescription.

If you do not have a 16s sample (which will result in better suggestions), you can use the generic a priori suggestions linked to below.
Proforma List

Special Studies: ME/CFS with IBS

IBS is a common morbidity for both ME/CFS and Long COVID. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does, but the degree of association (z-scores) are lower than prior special studies despite having a larger study population.

Study Populations:

ME/CFS with IBS111153
  • Bacteria Detected with z-score > 2.6: found 190 items, highest value was 8.4
  • Enzymes Detected with z-score > 2.6: found 182 items, highest value was 6.3
  • Compound Detected with z-score > 2.6: found ZERO items

The highest z-scores above are greater than other symptoms despite smaller sample size. This indicates that the causes have more of a signature and thus more homogeneous bacteria shifts then ME/CFS without IBS.

For those that have a sample processed thru BiomeSight software.

Interesting Significant Bacteria

All bacteria found significant had too low levels. Many Bifidobacterium species are significant

BacteriaReference MeanStudyZ-Score
Sporolactobacillus (genus)172368.4
Sporolactobacillus putidus (species)172368.4
Sporolactobacillaceae (family)170368.3
Bifidobacterium kashiwanohense PV20-2 (strain)319566.7
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)309566.6
Blautia wexlerae (species)602233736.1
Bifidobacterium gallicum (species)36996316
Bifidobacterium cuniculi (species)80226
Bacteroides finegoldii (species)27295505.6
Desulfovibrio simplex (species)219515.4
Succinivibrio dextrinosolvens (species)986885.3
Escherichia (genus)601111675.2
Phocaeicola sartorii (species)8203175.1
Haemophilus parahaemolyticus (species)66205.1
Lactiplantibacillus pentosus (species)123285
Clostridium chartatabidum (species)302505
Phocaeicola massiliensis (species)1385143585

Interesting Enzymes

All enzymes found significant had too low levels.

EnzymeReference MeanStudy MeanZ-Score
(2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (decarboxylating) (
(2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (
L-tyrosine:D-ribulose-5-phosphate lyase (isonitrile-forming) (
L-pipecolate/L-proline:NADP+ 2-oxidoreductase (
(R)-lactate hydro-lyase (
L-carnitinyl-CoA hydro-lyase [(E)-4-(trimethylammonio)but-2-enoyl-CoA-forming] (
acyl-CoA,ferrocytochrome b5:oxygen oxidoreductase (6,7 cis-dehydrogenating) (
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (
CMP-N-acetyl-beta-neuraminate:beta-D-galactoside alpha-(2->6)-N-acetylneuraminyltransferase (configuration-inverting) (
glutarate, 2-oxoglutarate:oxygen oxidoreductase ((S)-2-hydroxyglutarate-forming) (

Cross Validation

Looking at Medical Conditions with Microbiome Shifts from US National Library of Medicine we see agreements on many items (note that we have more bacteria identified because we have bigger sample sizes than those studies). Note that Escherichia (genus) is low, as was reported in the first study of the microbiome from Australia in 1998.

For the very few studies on ME/CFS with IBS

  • Bifidobacterium (genus)
  • Coprococcus catus

For studies of Irritable Bowel Syndrome 📚, we have agreement of these 7 bacteria

Bacillus (genus)2.1L
Bifidobacterium (genus)2.4L
Methanobrevibacter smithii (species)4.3L
Phocaeicola vulgatus (species)2.8L
Sutterellaceae (family)-2.3H
Turicibacter (genus)2.9L
Veillonella (genus)3.3L

For studies on Inflammatory Bowel Disease 📚, we have agreement on these

Bacteroides fragilis (species)2.5L
Bacteroidetes (phylum)2.1L
Bifidobacterium (genus)2.4L
Cyanobacteria (phylum)2.8L
Methanobrevibacter smithii (species)4.3L
Prevotella copri (species)3L

Bottom Line

The key take away is that Bifidobacterium levels appears to be a significant contributor. Lactobacillus is NOT (and likely is a contributor to oversupply of lactic acid causing brain fog). READ THE LABEL OF YOUR PROBIOTICS — you want Bifidobacterium without Lactobacillus.

The second probiotic to take is any of the E.Coli probiotics: Mutaflor (only available in a few countries) or Symbioflor-2 (available from Paul’s and ships worldwide). NOTE: Lactobacillus is hostile to E.Coli, a second reason to avoid those probiotics.

A Priori suggestions are now available:

The top items are below (more on the web page). Remember no microbiome will be an exact match and these lists may contain items to avoid; using your own microbiome data is always the best choice. As always, any changes should be reviewed by your MD before starting.