My primary concern for the last 20 years was been the condition known as Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). I deduced some seven+ years ago that the simplest explanation of the multitude of symptoms and abnormalities reported was a stable microbiome dysfunction. This explanation can also be applied to many other conditions. My focus is still on ME/CFS but I wish to make the data and algorithms available to people with any conditions. My old home page is here (dry technical).
The basic model that is supported by studies is:
DNA Snps that results in increased risk
Environmental changes of DNA (epigenetics) that further increase risk
Microbiome function that acts as a catalyst to the risk.
The microbiome is the simplest to alter technically — but very complex to alter because there are thousands of bacteria that interact with each other in the human body. DNA can also encourage some bacteria and discourage others. Example: Typhoid Mary is an excellent example of some one whose DNA and a nasty bacterial infection co-existed nicely.
Does changing the microbiome work for ME/CFS?
Answer is yes:
Recommended Site For Testing
With ME/CFS, there is always a nasty cost factor for testing. My usual recommendation is for the cheapest, high quality provider that provides information for upload to my analysis site. Some sites provide a mountain more of information — but the benefit from that extra information is almost nothing (and it adds $$$$ and complexity).
uBiome.com is shutting down. This had been my personal usual site because using a variety of techniques, the cost was $25/sample. Don’t order from there.
BiomeSight.com (EU based but serves the world) – discount code “MICRO” has integrated with my analysis site with automatic data transfer. For most people it is likely the best deal.
Thryve (US Based) is what I have used. Their reports may be processed here for independent suggestions. I would also recommend
Joining (free) The Gut Club – They have a discount code for Thryve — save yourself some extra dollars.
Who am I?
I am a citizen-scientist with reasonable scientist credentials: taught Chemistry and Physics at College Level; Master of Science, accepted for the PhD program, certified data scientist with R, one of the top mathematics and physics competition students in Canada during my university years, etc.
I am a closet academic — so I give links to my source of information everywhere and usually keep them to the highest quality sources (PubMed, professional journals). I have even had a letter of mine published in the Lancet.
This site — over 1200 blog posts published over the last 5 years. This is where I publish most. You can subscribe to get new posts by email.
Microbiome Prescription site – started in 2018. This is a massive data store with a variety of artificial intelligence algorithms applied to it. Almost 800 people have uploaded their microbiome results to it and many annotated it with their symptoms.
Microbiome Prescription Word Press – started recently. This is intended as a reference to the above site. Just essential pages and a bunch of homemade videos taking you through some features.
Facebook Site: Where I usually post new blog entries and the occasional odd note that is not worth a blog post. Make sure that you like it so you get notices of new posts.
Findings to Date
The assumption that bacteria shifts connect to symptoms appears confirmed using the upload microbiomes.
We have found statistically significant patterns of some bacteria to symptoms, see this post
We appear to have a high probability of correctly predicting symptoms from a microbiome report. See this post.
The Microbiome Prescription site is a theoretical site, that is, it works from the logical application of data and is not based on actual human experience. It does have the ability to create suggestions of things to take and to avoid to try reducing abnormalities in your microbiome. It supports multiple models and algorithms because we do not know which actually works best.
The site states that the suggestions should be reviewed by a medical professional. The source of the information is provided by links (hundreds of articles are cited).
As more data comes in, and more insight happens, there will be more posts and more features (some labelled experimental — because I am unsure of their accuracy) will be added. This is citizen science.
My ideas on this blog have evolved, as more and more information becomes available. This post is an attempt to bring readers up to date with my current thinking. I am striving to be transparent in my logic — showing the evidence I am working from, and my thought processes.
The data is available in an online collaborative python workbook for analysis. See this post.
Microbiome Definition of CFS/FM/IBS
A coarse condition that results from:
Low or no Lactobacillus, AND/OR
Low or no Bifidobacteria , AND/OR
Low or no E.Coli , AND/OR
A marked increase in number of bacteria genus (as measured by uBiome) to the top range
Most of these genus are hostile to/suppress Lactobacillus, Bifidobacteria, E.Coli
Several are two or more times higher than normally seen
The number of bacteria genus goes very high (using uBiome results), but most of them are low amounts.
(“Death by a thousand microbiome cuts” and not “Death by a single bacteria blow”)
The appearance of rarely seen bacteria genus in uBiome Samples.
A finer definition would be a condition with a significant number of abnormalities in the ‘Autoimmune profiles see this page for the current criteria (i.e. over 25%).
The specific genus and their interactions determine the symptoms seen — likely due to the over- or under-production of metabolites (chemicals). Other autoimmune conditions may share these core shifts. The specific high and low bacteria determine the symptoms if the person was the DNA/SNP associated with the symptoms.
Replace the metabolites produced by the missing bacteria
Replacing the metabolites should result in the reduction of symptoms associated with a deficiency of these metabolites.
See this post for the study references. These items should/could be done continuously.
“Baseline vitamin D level was found to moderate treatment effect on several outcome measures. Dry mouth and sleep disruption were reported more frequently in the placebo group. [Control took Lactobacillus helveticus and Bifidobacterium longum]” 
“heparin- or heparosan-treated animals were different from those of the saline-treated animals, with increased Lactobacillus spp. and decreased Enterococcus sp….heparin or heparosan may be used as an effective gut microbiota modulator by increasing the subpopulation of Lactobacillus.”  – Note:Berg’s anticoagulant therapy for CFS used heparin
“After the intake of apples (2 apples a day for 2 weeks) by eight healthy adult humans, the number of bifidobacteria in feces increased ” 
Unless the bifidobacterium and lactobacillus (B&L) are human sourced, there is almost zero chance of taking up residency. Taking probiotics will not allow B&L to get established. In fact, there are grounds to believe that most commercial probiotics actually reduce your native B&L. You want to encourage your native B&L. See this post for citations.
The E.Coli probiotics below are human sourced and known to take up residency in the human gut.
The best way at present to proceed is to order an analysis from uBiome. (Disclosure: I have no financial interest in this company.) When your get your results back, log in, click on the “Compare” tab, then go to “Genus,” and click on “ratio” twice, so the results are in descending order.
This is the “hit list” of what you are trying to reduce. DataPunk provides a nice summary of what we know about these. See, for example, Alistipes:
At this point, we run into a logistical challenge. You want to avoid items that are “Enhanced By” (which is in common across all of the high items) and take the items that are “Inhibited By” (which are not on any of the “Enhanced By” lists). You may also wish to reduce foods that are high in items listed in “Nutrients/Substrates.” It becomes a jig-saw puzzle! I have done this exercise for many readers’ uBiome results:
I have discovered that DataPunk is not absolutely current, and have started creating posts based on its data, and then added studies from 2016 and 2017 to the page. Past pages are below, for current list MicrobiomePrescription site.
Some of these items are contraindicated with a few uBiomes that I have reviewed. This likely is why person B reports no results while person A reports improvement. Example: Magnesium is usually very helpful — but there are a few cases where it encourages overgrowth of undesired bacteria.
Most probiotics do not take up residency. They are “here today, gone tomorrow”. Their primary role in my model is producing natural antibiotics against other bacteria. For example:
“Among those, seven Paenibacillus polymyxa strains showed the highest antibotulinal activity and the largest antimicrobial spectrum against C. botulinum strains. ”  – this is in Prescript Assist Probiotics
Probiotics should be rotated: 2 weeks on a specific one, then several weeks off. As a general rule, you want about 6-12 B CFU taken three times a day (or 2-3 times the recommended dosage) — but work up slowly because you may get be a major herx! In general, do not take Lactobacillus with Bifidobacteria or with E.Coli etc. Keep to one family per cycle. You do not want them to kill off one another!
Why 3x per day? Because almost none of them are detected after 12-24 hrs. So to keep them — and the production of natural antibiotics — going, you need to keep taking them during the day. See this post for citations.
The following probiotics commonly seem to help people with CFS/Lyme/Fibro:
Some probiotics, however, may make your symptoms worse! And, unfortunately, most commercial probiotics contains some of these. At the moment Bifidobacterium animalis, Saccharomyces boulardii and Lactobacillus acidophilus are on my best tototally avoid list.
“. The findings show that the six species of Bifidobacterium differed in their ability to relieve constipation. B. longum, B. infantis and B. bifidum were the most effective in relieving constipation, B. adolescentis and B. breve were partially effective and B. animalis was not effective. Furthermore, edible Bifidobacterium treated constipation by increasing the abundance of Lactobacillus and decreasing the abundance of Alistipes, Odoribacter and Clostridium. .” 
Working with the microbiome and autoimmune is like working with fragments of the dead sea scrolls. For many bacteria we can identify it — what inhibits or encourages it is not known to modern medical science. We have extremely thin slices of knowledge –Almonds enhances Bifidobacterium, Lactobacillus(B&L)as do sesame seeds. What about sunflower seeds? Peanuts? Cashews? We find that Walnuts help the bacteria that inhibits B&L — so we cannot safely generalize to “all seeds/nuts are helpful”.
In many cases, we find that healthy diet or supplements demonstrated to work for normal people have the opposite effect on CFS and other altered microbiome conditions. This is made even worst because most of the studies were done on males and most people with CFS are females. We end up having to swim up-stream thru good and valid suggestions — that are just wrong for us.
My model is simple to understand and allows us to filter many suggestions and candidates. With the availability of uBiome testing (without needing a prescription!) we have entered the age of explicit treatment based on your unique microbiome. We do not know the role of many bacteria involved. We do not know what will inhibit or enhanced all of these bacteria. Frustrating little knowledge!
On the flip side, many readers have reported significant improvement, reduction of prescription medication, etc. so the model and suggestions have potential and thus hope of remission! Microbiome studies are exploding on PubMed, a lot of research is being done and we can often borrow their results.
This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.
While working on a different blog post on brain fog, the light went on for a model that may explain newly developed alcohol intolerance in ME/CFS. People tolerated and enjoyed alcohol before ME/CFS so the cause is not DNA for these people, but some change caused by ME/CFS.
It gives an extensive list of suggestions with dosages and the studies they are based on, for example
It is a “all on-one-page” that is ideal to discuss with your medical professional.
WARNING ON LIFE STYLE SECTION
There are many nuisances in the studies cited that are missed or have misleading inferences. Simple example, “individuals who regularly exercised…. experience less fatigue”… could be restated as “individuals who experience less fatigue…. regularly exercised”. Causality is not in the evidence.
Also, Cognitive-behavioral therapy trials has many more than the single study cited — the majority of studies found that it did not help, or made people worse.
For the last few months I have been working with someone that runs a Long COVID support group. This has resulted in more modifiers being added. One of the outcomes has just been added to the site. She requested that a simplified set of suggestions be added to the site to make her life easier. This consists of items she picked from her experience dealing with the group.
Where to transcribe or upload data (depending on which test)
These simplified suggestions has been added everywhere (tell me if I missed a page). If you use GI Map or similar reports, it is available after you have transferred and return to adjust suggestions. You should see these options on most suggestion pages now. To get this new condensed report, just click the checkbox.
GI Map and similar
The report is a CDV file (loads into Excel or other spreadsheet programs)
After loading, into Excel, you will need to adjust column widths
I have not taken any probiotics for over 1 year. My medical treatment is pharmacological for type 2 diabetes, levothyroxine, hydroaltesone[Hydrocortisone], hydroferol[vitamin D3 analog] 1 a month, statins, Omega 3 and fenofibrate, I have not taken probiotics.
Symptoms persist, abdominal bloating, tiredness, unrefreshing sleep, PEM, sore throat, lack of energy, exercise intolerance, visión changes, all symptoms of ME/CFS
Also the increase un body weight has been considerable and it is not possible for me to lose weight, my complexion was thin.
The latest sample was from BiomeSight so the number comparison below is more out of interest than being a truly valid comparison (which would be same lab to same lab). On the surface of the comparison we see what appears to be significant improvement on high percentile bacteria but an increase of low percentile bacteria.
Using the various canned criteria (Jason H, Medivere, Metagenomics, MyBioma, and XenoGene), there has been no change. By “canned”, we mean the bacteria picked by various sources that are important –usually at the genus or family level. The criteria below these lines are sensitive to the lab and the quality of the sample.
Lab Read Quality
Bacteria Reported By Lab
Bacteria Over 99%ile
Bacteria Over 95%ile
Bacteria Over 90%ile
Bacteria Under 10%ile
Bacteria Under 5%ile
Bacteria Under 1%ile
Different Labs – Items Skipped
Outside Range from JasonH
Outside Range from Medivere
Outside Range from Metagenomics
Outside Range from MyBioma
Outside Range from Nirvana/CosmosId
Outside Range from XenoGene
Outside Lab Range (+/- 1.96SD)
Comparing Samples (limited)
In the old analysis I was using ratios to mean. I have since moved on to percentiles. The table below looks at the top items and compare to percentiles. Note: there can be differences between labs on what they called bacteria (see The taxonomy nightmare before Christmas… (2019)).
REMEMBER: The order does not reflect effectiveness — it reflects the amount of research available, hence the term Confidence.
We have a variety of items listed that are usually suggested for ME/CFS. The reason that they are suggested is that blood tests show low levels. I am becoming inclined to suspect that the low levels in the blood is because of greedy bad bacteria in the microbiome that consumes them before it get to the blood. SPECULATION: Taking them as a supplement, feeds the bad bacteria and keeps ME/CFS going.
Vitamin B injections are likely fine, probably good! “Patients with myalgic encephalomyelitis (ME, also called chronic fatigue syndrome) may respond most favorably to frequent vitamin B12 injections” 
I would suggest trying the above suggestions (after it is reviewed by your MD), and retest every 4 months. Looking at A History of Several 16s Tests and Suggestions which was done on another ME/CFS person, we saw improvements in the he various canned criteria (Jason H, Medivere, Metagenomics, MyBioma, and XenoGene) after 3-4 months.
This person did a microbiome analysis thru Biome Sight, tranfered the data to Microbiome Prescription where Dr. Artificial Intelligence did an analysis based on over 20 million facts.
I have a set of questions about the selection of probiotics during the course of the microbiome treatment. My first week-and-a-half using the Dr. AI plan went fine, with no notable events. I did recover a significant amount of strength in the same time—from being unable to drive or stand comfortably for long, to being able to drive, walk, do a few chores around the house—but I also have a general capacity to recover so long as I rest, so I can’t say to what extent the treatment was responsible. It’s possible that the rate of recovery was increased. Regardless, I’ve run out of probiotics, so I’m looking to buy new ones.
For cost per CFU, I am drawn to Custom Probiotics. Having not herxed at all during the initial course of probiotics, I am also thinking I need to crank up the CFUs a little. However, given the unit price, I just want to make sure my decisions are being informed by a reasonable grasp on probiotic use for CFS/Long COVID. Hence, some questions for you, if you have the time:
My first dilemma: a singular, large, multi-strain mixture of B&L, or a post-purchase combination of a small number of single-strains of B&L? Generally, it seems necessary to take at least one Bifido. and one Lacto. per treatment cycle, so long as B&L are both recommended and one is not taking a probiotic antagonistic to B&L. My inclination, especially given unit cost, was to request Custom Probiotics make me a mixture of my top B&L. Using Special Studies, for example, I get B. longum, L. plantarum, L. acidophilus, L. paracasei, and B. lactis—so, perhaps I could request a singular mixture of these bacteria. But, I’ve also seen you refer to the use of one or two single-strain probiotics from Custom Probiotics at a time, which, in addition to some other concerns, gives me pause. Would you instead favor, for example, combining separate B. longum and L. plantarum single-strain probiotics, with no other strains in the same cycle, over my big mixture?
Answer: I would advocate just getting a single species bottle and trying for 2 weeks, then rotate to a second and then back. My first choice would be alternating between B. longum and L. plantarum, noting carefully what the response to each is. Start at a dosage similar to what you were taking and double the dosage every second day until you are at the desired dosage. The problem with a mixture is that you do not know which one is causing good or bad responses.
Is “two weeks on, two weeks off”, or something comparable, a hard-and-fast rule for the pace of the probiotic cycle? Or, are there other good metrics for judging when to stop or start a probiotic? For example, I was wondering whether one might continue a particular probiotic beyond two weeks if it’s continuing to cause a herx at the two-week mark. (Of course, one should stop prematurely if the herx is too extreme.)
Answer: The two week rotation is based on the Jadin’s Protocol for Antibiotics. see Rotation — Essential for Changing the Microbiome. There is no problem stopping early due to herx. Personally, I had to crawl on the floor to get to the washroom from my first taking of Mutaflor, in hindsight, I did not need to push so hard. Rather reduce dosage or stop. A comfortable herx lasting a couple of hours and then fading is what I like — it answers the question of “Is it working” but allows a reasonable day.
I noticed E. coli is my top KEGG recommendation, but is weakly recommended (sub-50 Priority) in the consensus suggestions under some circumstances, and not recommended at all in a Special Studies consensus. Is E. coli still favorable in that case?
Answer: Unfortunately we are dealing with fuzzy data everywhere. The numbers do not indicate effectiveness, rather reflects the number of studies that reports shifts of bacteria in a positive or negative direction multiplied by the estimated importance of shifting, hence the term “confidence“. Given you observations, I would suggest trying one bottle of Symbioflor-2 (which is done by drops and persists) and include it in the rotation above as a third item (or a fall back if one causes problems)
Questioning a previous assumption, is it actually necessary to take both B&L at the same time, each time? I see from the database, for example, that L. plantarum increases both Lacto. species and Bifido. species. This would imply it’s not necessary to take a Bifido. with L. plantarum, right?
Answer: NOTHING IS NECESSARY. The goal is to produce a list of items that have a higher probability of helping (or hurting for the avoids). You can cherry-pick from the list as you finances or situation permits. Doing the avoids is often significant, recently I got an email from someone who cut the avoids immediately while trying to figure out the new menu — she noticed improvement within days..
I know biofilm breakers and anti-coagulants are a good idea for antibiotic pharmaceuticals/herbs. But, what about probiotics? I can imagine dissolving biofilms with bromelain is helpful so the bacteria in the probiotics can outcompete what’s hidden too. But, what about the other big players—nattokinase, lumbrokinase, etc.? Do probiotics interact with these supplements favorably?
Answer: I do not know, but I know that some probiotics produce bacteriocins (natural antibiotics), so I would say yes. BUT A WORD OF WARNING — they may also increase or produce a severe herx. So go slow with them. Do not take them until at least day 3 of a new probiotic. Again, the goal is one-item at a time, taking notes; not tossing the kitchen sink into your supplements and hoping something works.
I’d like to thank you for all the support you’ve offered me over the past few months. I truly appreciate the time you’ve spared to answer my questions, and I am sure I will have you to thank when this illness has resolved. I hope you have a great weekend!
Follow Up Questions
Regarding your response to my second question: Thank you, this makes sense. I guess Jadin’s protocol can be generalized to anything that modifies the microbiome, give or take. Nonetheless, are there any circumstances where it would be sensible to extend the use of a particular probiotic past the two-week mark? I’m recalling a hypothesis you share in your notes on your 4th relapse, to the effect of, “If a modifier appears to be resolving symptoms, continue using it, even if the database suggests switching in the most recent analysis.” This was proposed with regard to the use of one modifier over another (i.e. keep using L. plantarum if it’s helping, even if the latest priorities from the database suggest some other probiotic would be more helpful). But, I wonder if this could be extended to the choice to cease the use of a particular modifier at the end of a two-week cycle. If L. plantarum is continuing to cause a herx at the end of two weeks, or if my symptoms keep improving with its use, could that (or any other reason you might know of) be taken as a sign to keep using it? I’m assuming no, since other probiotics might help as well and there is a general risk the microbiome develops resistance if one pushes the same modifier too long. But, I am curious where the boundaries of our rules are.
Answer: I would agree that it is a viable path, with the caution being — to monitor that the improvement keeps happening significantly. I would not extend beyond 6 weeks. You will rotate back to it soon enough.
Have you heard of anyone having adverse reactions to the anti-coagulants? Easy bruising is the obvious one, but I have in mind other problems. In particular, while not clinically acceptable perhaps, a minority of Amazon reviews of Doctor’s Best “High-Potency Serrapeptase” (at least a fraction of the one-star reviews, which would constitute at most 6% of the 7.2k total reviews for the product) report frightening GI issues, and circulatory issues that do not appear to fall under the category of “easy bruising”. A similar distribution is present for the other brands of serrapeptase. There are many fewer reports of illness for lumbro. and natto. on Amazon, seemingly, but I can’t say for sure. Based on your experience or knowledge of the literature, does this sound familiar, or explicable?
Answer: Yes, it is one reason that I suggest using a MD to determine the appropriate ones. Each ant-coagulant has different impacts on the coagulation cascade. I was able to keep working with over the counter anticoagulants for a while (hoping that things would correct themselves), the moment that I saw easy bruising, or cuts that did not stop bleeding, I bailed from anticoagulants and went on sick leave and then disability the next day. I learnt from deep testing for inherited or acquired coagulation factors (at the former Hemex Labs with David Berg) that my issue was just one (Prothrombin 20210 A/G a.k.a. Factor II mutation). My eldest daughter from an ex-wife had 3 factors (which likely explained some of the cognitive problems and behaviors with her that resulted in her becoming an ex).
Taking anticoagulants that works on platelet aggregation (i.e. aspirin, etc) would not have an effect. Research for substance that impacts the specific issue(s) impacting you is usually advised. I copied a chart below to illustrate the cascade — you may have an issue with just one step.
Any thoughts on the use of bovine organ extracts as a supplement? Heard about bovine thymus extract causing a herx and symptom improvement in a handful of cases, and my naturopath just prescribed me something that contains bovine adrenal extract. The theory, I understand, is that the bovine organ supports the function of the same organ in the human body. So, bovine thymus enhances function of one’s own thymus, leading to intensified immune response to overgrown bacteria in the microbiome (perhaps immune system too weak otherwise under conditions of dysbiosis), leading to experience of herx and symptom improvement. I imagine the mechanism is something analogous for the adrenal glands. Good data is not plentiful as I understand, but maybe there’s something to it. No clue. Saw some papers, but they were mostly theoretical.
Answer: You used several key words: “handful of cases” and theoretical. My first step was going to Clinical Trials to see if there were any. There was NONE. This implies that there are no serious ongoing studies of it. The same results from the PubMed. Doing a wider search I found the following:
1941 article: QUANTITATIVE TREATMENT OF PERNICIOUS ANEMIA RESPONSE TO INITIAL MASSIVE DOSE OF LIVER EXTRACT IN RELAPSE
1962 article: IMMUNIZATION WITH ADRENALS OF FOREIGN SPECIES
So, my impression is that once upon a time, a long long time ago, there was interest in it but its use was abandoned my main stream medicine. There is neither evidence of it being effective nor evidence of it being harmful.
I did a repeated search with “bovine adrenal’, a more specific item. It found 7 in the clinical studies, none involving humans. On PubMed, I searched for “bovine adrenal” supplements and got 12 results, scanning them there was no human studies. So my own take is simple, there is no clean clear science supporting it, hence it gets toss to the back end of things to consider.
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 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.
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.