Quick start to 2 blogs and an analysis site

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:

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons , 2018

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

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.

The Sites

  • 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.

These findings can be independently confirmed by using the public shared data at: http://lassesen.com/ubiome/

Tools to Help

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).

Evolving Story

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.

Video to kickstart using your microbiome use

Overview of this Blog and the Microbiome

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.


Notes to Treating Physicians     Quick Self Start on treating CFS


Analysis of Microbiome/stool with recommendations

Site: has moved to http://microbiomeprescription.azurewebsites.net

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.

Other Supplements Reported to Help

Bootstrapping Bifidobacterium and Lactobacillus

The items below were found in studies to increase bifidobacterium and lactobacillus:

Unless the bifidobacterium and lactobacillus (B&L) are human sourcedthere 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.

Bootstrapping E.Coli

The E.Coli probiotics below are human sourced and known to take up residency in the human gut.

  • Core: D-Ribose a preferred food that it uses
  • Mutaflor probiotics — E.Coli Nissle 1917
  • Symbioflor 2 — multiple strains

Dealing with the other microbiome shifts

The other microbiome shifts appear to be in different clusters of microbiome shifts. This 2017 paper by Peterson, Klimas, Komaroff, Lipkin (and a stack of other CFS researchers) makes that clear in its title: “Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome”.

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.

nihms-731256-f0001

Src: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754147/

General Suggestions (no uBiome results)

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.

Probiotics

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:

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 to totally 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. .” [2017]

On my neutral list (no clear benefit) is Lactobacillus Plantarum.

Teas

Some teas can also be antibiotics (among other roles). There are two teas that seem to produce significant results quickly:

Again, rotate and, if practical, change brands too. Their antibiotic compounds are different from different sources.

Herbs and Spices

The best choice needs examination of your microbiome (i.e. uBiome results) and doing the work cited above.  Survey results found:

  1. Neem and Oregano with 80% improving
  2. Olive Leaf and Licorice with 56% improving
  3. Thyme with 50% improving
  4. Wormwood and Tulsi with 33% improving

Other things

If you do not know your microbiome, then see https://cfsremission.com/reader-surveys-of-probiotics-herbs-etc/  for suggestions. Your results will vary because your microbiome vary.

Thick blood is an issue also — but here things gets more complicated and not suitable for this recap.

Antibiotics can have a role — but getting prescriptions for the right ones can be a major challenge.

Metabolism Shifts

From volunteered data, we can identify some distinctive shifts, see Metabolism Explorer Summary

Bottom Line

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.

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:

SymptomReferenceStudy
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 (1.8.98.5)
  • CoB,CoM:ferredoxin oxidoreductase (1.8.7.3)
  • CoB,CoM,ferredoxin:coenzyme F420 oxidoreductase (1.8.98.4)
  • coenzyme B,coenzyme M,ferredoxin:formate oxidoreductase (1.8.98.6)
EnzymeReference MeanStudy MeanZ-Score
6-amino-6-deoxyfutalosine deaminase (3.5.4.40)17867664.5
chorismate hydro-lyase (3-[(1-carboxyvinyl)oxy]benzoate-forming) (4.2.1.151)17627614.5
S-adenosyl-L-methionine:3-[(1-carboxyvinyl)-oxy]benzoate adenosyltransferase (HCO3–hydrolysing, 6-amino-6-deoxyfutalosine-forming) (2.5.1.120)17307524.5
dehypoxanthine futalosine:S-adenosyl-L-methionine oxidoreductase (cyclizing) (1.21.98.1)17207534.5
hydrogen-sulfide:flavocytochrome c oxidoreductase (1.8.2.3)12693024.1
[SoxY protein]-S-sulfosulfanyl-L-cysteine sulfohydrolase (3.1.6.20)12903144.1
CTP:5,7-diacetamido-3,5,7,9-tetradeoxy-L-glycero-alpha-L-manno-nonulosonic acid cytidylyltransferase (2.7.7.81)12343154

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.

https://microbiomeprescription.com/Library/CitizenScience

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:

SymptomReferenceStudy
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) (1.14.20.10)131216.3
(2S)-3-(4-hydroxyphenyl)-2-isocyanopropanoate,2-oxoglutarate:oxygen oxidoreductase (1.14.20.9)131216.3
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)14384255.3
L-tyrosine:D-ribulose-5-phosphate lyase (isonitrile-forming) (4.1.99.24)103325.3
L-pipecolate/L-proline:NADP+ 2-oxidoreductase (1.5.1.21)177475.2
(R)-lactate hydro-lyase (4.2.1.130)15143265.1
L-carnitinyl-CoA hydro-lyase [(E)-4-(trimethylammonio)but-2-enoyl-CoA-forming] (4.2.1.149)13713285.1
acyl-CoA,ferrocytochrome b5:oxygen oxidoreductase (6,7 cis-dehydrogenating) (1.14.19.3)10092615.1
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)13894315
CMP-N-acetyl-beta-neuraminate:beta-D-galactoside alpha-(2->6)-N-acetylneuraminyltransferase (configuration-inverting) (2.4.99.1)66205
glutarate, 2-oxoglutarate:oxygen oxidoreductase ((S)-2-hydroxyglutarate-forming) (1.14.11.64)12323165

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

BacteriaZ-ScoreDirection
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

BacteriaZ-ScoredIRECTION
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:

https://microbiomeprescription.com/Library/CitizenScience

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.

Under the tongue and Brain Fog

The alternative title would be “Neurological issues and sublingual”. I got an email this morning from a ME/CFS person which reminded me of what I do often and I thought that I should share/remind others.

Reporting back. I tried  B1 benfotiamine again. I was feeling tired for no reason  so gave it a shot. I just wanted a low dose and so I opened the cap and sprinkled a quarter in my mouth. I usually take 1 cap. Huge effect. Felt like my muscle and brain came alive. In the past when I’ve taken b1 for a while it usually wears off or causes issues though so my question is how would I used Dr. AI to see if I have a deficiency of b1 and if need be what items to shift the microbiome. I’ve tried it prior to crashing  / PEM before and it didn’t stop it but I will do it again since it’s been a while.

For other experiences of ME/CFS with benfotiamine (a special form of Vitamin B1), see my earlier post from 2015

I have done many things sublingual, including heparin (much cheaper and appears just as effective than Low-molecular-weight heparin to deal with coagulation issues, and no injections!). My personal favorite is Piracetam which works far far better to get a tired brain working than strong coffee (at least for me).

The logic is simple, the amount that gets to the brain (which is close by) is much more than being processed through stomach acid and slowly working it way to the brain via the blood.

There is considerable literature supporting this, a few examples:

Note that the instructions for Symbioflor-1 probiotics, ” Take the drops, hold them in the mouth for a while and gargle with them before swallowing.” could be described as sublingual. Taking probiotics sublingual is not common practice…

Which ones?

There is no easy answer. Often taste can be a factor for tolerance of this approach. It may be a good exercise to try many of your supplements (one at a time) via this route and seen what has significant impact.

REMINDER: Rotate, rotate, rotate. A common complaint is that “a supplement benefit wears off”. In terms of the microbiome, this is expected from almost everything. The bacteria population adapts.

The importance of a large variation of diet with ME/CFS

For items like antibiotics and probiotics, I have for a long time been a strong advocated for continuous rotation. The original source for this attitude was Cecil Jadin’s treatment protocol for occult rickettsia (which originated with the Pasteur Institute for Tropical Medicine). This was followed by reading studies finding that rotating or even just pulsing (2 weeks on/ 2 weeks off) was more effective in reducing bacteria than continuous. Probiotics often function via the natural antibiotics they produce (a lot of prescription antibiotics originated with bacteria); hence probiotic rotation became part of my preaching.

If you have microbiome related issues, my soapbox has been “your goal is make the stable dysfunctional microbiome, unstable. Today I read a study on Nature that further clarifies what may be needed.

Together, these findings suggest that the human gut microbiome’s metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient. The dynamics of this ecological memory also highlight the potential for intra-individual microbiome variation to affect the design and interpretation of interventions involving the gut microbiome.

Ecological memory of prior nutrient exposure in the human gut microbiome [2022]

If the goal is to make the microbiome unstable, then this gives some clear indication of strategy.

  • Every two weeks change the dominant starch – for example, if pasta is a regular meal item then
    • Made from glucomannan—a starch found in the konjac yam/ Konjac Flour (Source)
    • Made from red lentils and quinoa (Source)
    • Made from white rice flour, organic amaranth flour (Source)
    • Made from chickpea flour, organic yellow lentil flour, organic red lentil flour, organic kale powder, organic spinach powder (source)
  • Every two weeks change dominant proteins source
    • Fish
    • Pork
    • Lamb
    • Duck
    • Chicken
    • Turkey
  • Change vegetables and fruit too…
  • Change main spices used….

The key aspect is that every new addition results in a change of the microbiome. If you have microbiome issues, that is what you want to do. You do NOT want to take the same supplements, herbs, spices, vitamin or comfort food – continuously. You want to shake things up!

Phospholipids, the Microbiome and ME/CFS

For almost a decade I have suspected that there was an interaction between the microbiome and Antiphospholipid syndrome (APS) also known as Hughes Syndrome (after the MD, see below). This is also called  “sticky blood syndrome” [HealthLine]. For some researchers, it is deemed to be a significant contributor to fatigue in Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [1999 D. Berg] and likely also applies to Long COVID. My own singleton experience seems to confirm it for myself.

A reader asked about phospholipids on Facebook today, so I revisited available literature

This article by Graham R.V. Hughes, MD, FRCP (the discoverer) in 2016 is well worth reading.

For me, APS/Hughes syndrome is very much a neurological condition. Brain function does seem to be especially targeted—the more APS patients one sees, the wider and wider the neuropsychiatric ripples spread.

APS: What Rheumatologists Should Know about Hughes Syndrome • By Graham R.V. Hughes, MD, FRCP

Of course, running off the experience of just one, or even a few people, is not the best practice. Testimonials suck because of rose color glasses, fake testimonials, mainly positive responders report, and placebo effects. So what does the literature state. First there is some literature that are general discussions without the type of detail that I would love to see:

Then we come to this article: Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity [2019] which uses one of my favorite information source, the Kyoto Encyclopedia of Genes and Genomes. “We found that PGs were positively associated with microbiomes enriched with endotoxin-synthesis genes and associated with markers of inflammation.”

Digging further we find:

 Bacteroides thetaiotaomicron, Actinomyces massiliensis, Pseudopropionibacterium propionicum, Corynebacterium amycolatum, Ruminococcus gnavus and Roseburia intestinalis[2021] lead to the formation of pathogenic T‑cell and autoantibody responses via the cross-reactivity with autoantigens (Ro60, dsDNA and ß2 glycoprotein I). 

The role of the microbiome in lupus and antiphospholipid syndrome [2020]

M. pneumoniae and Streptococcus spp. infections, which are among the most prevalent bacterial infections in children and young adults, were linked to the occurrence of aPL. …. an anaerobic bacterium Fusobacterium necrophorum, although a variety of other bacteria such as streptococci, staphylococci, and enterococci may be also responsible…. a specific change in the gut microbial composition in APS patients. Particularly, a decrease of bacteria belonging to the genus Bilophila and overgrowth of bacteria of the Slackia genus were shown…  enrichment by Slackia spp. and by the lower abundance of butyrate-producing Butyricimonas 

Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation [2019]

More discussion of mechanism is in The Role of the Gut Microbiota in the Pathogenesis of Antiphospholipid Syndrome [2015]

Bottom Line

APS only requires one of the bacteria above to trigger it. In terms of using Microbiome Prescription, I would look at Bilophila and Butyricimonas – if below 50%ile, hand pick it, then look at Slackia, if above 50%ile then hand pick it. Check the other bacteria cited above, and if any are over 75%ile, hand pick those. “It only takes one rotten apple to spoil the barrel” seems to apply here.

I have added APS to my PubMed reference list:

From https://microbiomeprescription.com/library/PubMedCitation?CondId=88

Personal Observations

I checked my samples from my last ME/CFS flare and found that Bacteroides thetaiotaomicron went from 73%ile on first sample after onset, to 96%ile on second sample, down to 79%ile, then 70%ile then 20%ile a few months later with recovery and returning to work. The key triggering bacteria will likely be different for each person but you at least have a candidate list to work from.