Evidence of ME/CFS improving using Microbiome Data

Overview

Short bio: 35yr Male have had ME/CFS for about 7 years, see A review of a ME/CFS Microbiome for prior review plus backstory. This was my review for “A – Thryve:2021-11-21 self” below.

This person has had done three samples, so we will both look at the latest sample and across samples.

  • A – Thryve:2021-11-21 self
  • B – Thryve:2022-03-15 self (he used the microbiome prescription site himself to get next course adjustment)
  • C – Thryve:2022-05-16 self (this review)

The key questions focus on objective improvement and subjective improvement.

General Health Issues

The evenness of Genus and Species across percentile is shown below

AABBCC
PercentileGenusSpeciesGenusSpeciesGenusSpecies
0 – 91116691115
19-Oct123015301927
20 – 29193120241231
30 – 39183523451633
40 – 49162420371830
50 – 59213125452133
60 – 69182017301422
70 – 79162311281623
80 – 8951416241321
90 – 993141320514
Total139238166292145249
Std.Dev.6.057.715.7211.104.607.02

My reading is that at the Genus level, the microbiome is stablizing. An ideal microbiome would have a Standard Deviation of 0.0 (i.e. the appropriate percentage is in each class). We see for Genus move from 6.0 -> 5.7 -> 4.6. Species have a far greater degree of randomness because may species are not identified, most genus are identified.

Potential Medical Conditions Detected

The count has been similar: A:3 B:6 C:2 with the one items in common being Allergies.

Unhealth Bacteria

The counts were similar between all samples: A:18, B:20, C:21

Dr. Jason Hawrelak Recommendations

We had significant improvement between the first two samples and a slight loss going to the third: A: 56.5%(5) B:95.5% (8) C: 89% (7)

AI Computed Probiotics

Sample A
Sample B
Sample C – Nothing

AI Suggested Supplements

Using the default 10% level, we found samples A and B only suggested one supplement. C suggested 2 (L-Histidine and manganese). I looked up the item from A and B and saw that it had continued to improve. 🙂

SupplementsABC
beta-alanine 7.39.217.3

Has there been positive change?

My reading of the above objective numbers is yes in several vectors. There was nothing show a clear negative change. Somethings stayed put — that is fine, it is small steps. As the picture below illustrates, it is not a direct line/tunnel through the mountain ranges of dysbiosis, we have to work our way across passes and valleys.

The “I don’t feel better” quicksand

I have too often seen — especially with people suffering from Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) — patients giving up on a course of action because they reached a point where they may state “I don’t feel better from doing this, so I am changing…”. For these people, this is often caused by several factors:

  • They do not remember how they were actually 2 weeks or 2 months ago…
  • Their MD have no objective tests to show progress
  • They expect significant constant change constantly (they are frustrated waiting for improvement)

Using the microbiome and repeated testing, they can get objective measurement of changes instead of relying on subjective measurement being done under the influence of brain fog with memory problems.

In this person case, we do see objective improvement of the dysbiosis. What about subjective?

“You’re welcome to mention I have noticed improved sleep and lower anxiety despite my good and bad bacteria shifting around “

From the reader

Moving Forward

As reviewed above, we have no KEGG suggested probiotics, but do have these supplements suggested:

On a personal note, I used NADH during my 1999-2000 relapse (1st time diagnosis). I eventually switched to 400 mg of flushing niacin twice a day (after MD checked my liver function see facts) and have continue to do so (with liver being tested every year).

Getting suggestions based on US National Library of Medicine Studies

As is my pro forma approach, I did each of the following (with number of bacteria picked after):

The new layout of the consensus page is shown below

Remember these are blindfolded suggestions, items like polysorbate 80 as a supplement is not recommended by any MD, it is in many supplements. [src]

My suggestion for 3 probiotics to rotate thru are:

For more information on probiotics see the bottom section of this recent review.

For supplements, there are only 3 easily accessed items that are positive, everything else is negative impact!!Ferric citrate (iron supplement), magnesium (commonly used for ME/CFS) and vitamin k2

For other things, see the video or the suggestions on your microbiome.

Bottom Line

You are making objective progress. A word of caution, if some of the items that you are currently taking on the avoid list, slowly remove them by reducing amount and watching for potential adverse effect. Some of the positive objective changes may be due to them (there is a risk of a feedback loop: if you are taking them, they are not needed BUT it you stop taking them, your microbiome may devolve to a state needing them).

Last – Using Symptoms

This is EXPERIMENTAL. It is a thought experiment and I am still learning it’s behavior. For some symptoms it may reduce awesome results, for others it may improve one set of symptoms at a cost of other symptoms getting worst. I picked two of the more unusual symptoms that he had:

  • Comorbid: Methylation issues (MTHFR)
  • Immune: Chronic Sinusitis

This resulted in this list being selected with a very strong Filter (first time I have seen this)

RankNameYour valuePercentile
class Flavobacteriia217
order Chromatiales219.4
order Flavobacteriales217
order Marinilabiliales2113.5
phylum Tenericutes429.5
species Bifidobacterium bohemicum2111.8
species Eubacterium ramulus872095.5
species Prevotella disiens94684.1

I would suggest using it to increase the priority of some items that are positive suggestions in the consensus list, I would not go with using this set of suggestions alone.

Questions from Reader

  • Ferric Citrate ,  haven’t been able to find this type?🤔 Have you seen it anywhere? Also how would one figure out the dose for gut bacteria shifting?
    • I am an ex-science teacher and thus know it more common name, Iron CitrateSwanson and others sells it.
  • Bacillus- taking terraflora , think I’m up to 6 caps. I saw in a study I need to get to 20 !!
  •  …I also have prescript on hand BUT that has a lot of other SBO strains. Would you stuck to TERRAflora for now?  
    • I would keep the Prescript Assist on the shelf, and keep to Terraflora, I would keep increasing the dosage every second day until the bottle was finished. I would look around for ones with similar probiotics for the next cycle, for example Youtheory, Spore Probiotic, 6 Billion CFU, 60 Vegetarian Capsules – for two reasons:
      • Cheaper per BCFU (and also higher BCFU per dosage)
      • Different strains often helps because they produce slightly different products
  • Miyarisan , I thought I saw this in my results somewhere , maybe it was far down the list…would you save or finish if you had my results?
    • It is on the list, I would finish it before starting the next cycle of probiotics (REMEMBER: we want to be rotating the probiotics – not take them continuously)
  • Akkermansia – I have 2 bottle of this stuff actually from pendulum . I read you and your wife has taken it. How much did you take or I know it’s a new product but if you’ve seen a study with dosing please let me know. 
    • The one existing study used 10 BCFU/day, and the bottle reads 0.4 gm. Lacking more information, I would just keep to the bottle recommended dosage.
  • NADH- I have the flush stuff and cq10? Do you think that combo works or does it have to be Nadh?
    • Personally, I found flush niacin had greater impact and still look forward to my morning flush to get the mind working (it improves oxygen delivery because it’s a vascular dilator). Assuming you can tolerate the flush.

ALWAYS REVIEW WITH YOUR MEDICAL PROFESSIONAL FIRST

Intelligence of Nature “RESTORE” – still danger?

A reader emailed about my earlier post, RESTORE for gut health Danger Will Robison! I am a firm believer in evidence based medical treatment. Ideally the source of the information will be a study on the US National Library of Medicine (PubMed). If it is not studied, IMHO there is a significant risk of danger.

He writes:

I purchased  a bottle of RESTORE a couple years back which was manufactured by Bionic Sciences LLC which is now ION* Gut Health and the company changed its name to Intelligence of Nature  the ingredients of my RESTORE bottle says Aqueous Humid Substances ( Terrahydrate). 150mg per teaspoon and now the ingredients on the ION* bottle says Humic Extract from ancient soil 5mg per teaspoon …
Are we talking about the same product here???

I proceeded to their site to see if they have any evidence. They linked to studies, I downloaded many of them:

My first impression is that we have gas-lighting here. It has not been peer-reviewed, but most people will not registered the “pending”. It has not been published.

Another of their studies seems like a deliberate attempt to mislead, iMedPub seems to be an attempt to mimic PubMed… Going to that site I see “All Published work is licensed under a Creative Commons Attribution 4.0 International License” and who owns that site is willfully hidden (checking its registration) and it is a “we publish anything for a fee site” – “Hence, the Journals operate solely through processing charges we receive from the authors and some academic/corporate sponsors. ‘[src]

So what is in it? They appear to have obfuscate the ingredients – Dropping the list and replacing it with a non-descript “Humic Extract (from Ancient Soil)”. In other words, I can get the same thing by just going to any National park and collecting some soil!!

There are studies for other products

Bottom Line

The firm is my issue, not the concept. Studies have shown that results depend on the source/content of the humic acids. They have failed to provide scientific information on the content. They have failed to publish respectable studies and the studies on their site appears to be gas-lighting. Their prices is $72 for a 2 month supply… well, I can get 25 pounds of Granular Humic Acid Powder – 25lb Bag, for $20 from Walmart!

I have also commented in the past” A teaspoon of good soil will likely help many microbiome issues” (i.e. the hygiene hypothesis). Most of the bacillus probiotics are soil based bacteria.

Follow up Microbiome Analysis from a prior ME/CFS post

This is a follow up to my blog post of Dec 30, 2021. Rosacea, Circulation and mild CFS. The person has tried the suggestions, and now we will attempt to see what the consequences are and the next set of suggestions.

Remember, the suggestions are based on mathematical modelling using clinical studies on study populations, so they may work or not work for individuals.

Reminder:
I am a computer scientist and a statistician. I am not licensed to practice medicine, and where I live has strict laws about ‘appearing to practice medicine’. What I can do for readers is to write a public blog (anonymous) from your data and back story as an education post on using the software and the statistics it produces. I cannot consult. The content should be reviewed by a medical professional before implementing.

High Level Measures

Bacteria Selected using Expert Criteria

MethodPriorLatest
Use JasonH (15 Criteria)56
Use Medivere (54 Criteria)56
Use Metagenomics (59 Criteria)56
Use Nirvana/CosmosId (36 Criteria)56
 Use XenoGene (22 Criteria)56
 Standard Lab Ranges (+/- 2 Std Dev)86
Box Plot Whisker3027
Kaltoft-Moltrup Normal Ranges7884
Percentile in top or bottom 10 %6399

My impression is that the microbiome has become more diverse, in one sense, unstable. The increase in the number of bacteria types reported (591) moved it just above the typical count for BiomeSight (578). My personal experience is that this is a good sign, the microbiome is changing, I experienced this spike is variety before my microbiome settled down into a new, healthier normal.

Symptoms Change

“This things has improved:

  • Less bloated
  • Seborrhoeic dermatitis is gone 
  • Better stool
  • Better libido

Using the regression for all symptoms we had regressions for, we had 154 improved out of 209 items, or 74% had improvement in the prediction of symptoms.

Overall: Appears to be Improved

This person was a challenge originally because there was no dominate shifts or “smoking guns”. Being at the 99+% for Dr. Jason Hawrelak recommendations and the same items returned from other expert suggestions (many with more criteria) had no significant change. Supporting improvement: Increase in bacteria types closer to typical; significant decrease in number of Unhealthy Bacteria; improved symptoms; and last, prediction of symptoms had a major improvement.

Next Round of Suggestions

After the above sample, he actually started two more items:

  • 10 days with doxycycline
  • started to take rosemary “Feels pretty good taking it. ” 

Probiotics

There are many Ways of Choosing Probiotics, I will look at two below:

KEGG AI Computed Probiotics

The differences actually shocked me, a very very dramatic difference. On the current sample I see what is often on ME/CFS patients list appear at the top: miyarisan (jp) / miyarisan with also L. Plantarum Probiotic Powder. This suggests that he is moving towards/through a more typical ME/CFS microbiome. Given that he has issues but everything appeared normal or good, I take this as a good sign – we are exposing the issues.

Prior SampleCurrent Sample
CustomProbiotics.com / L. Brevis Probiotic Powder
2
CustomProbiotics.com / L. Rhamnosus Probiotic Powder
2
digestive care
2
Metabolics / Lactobacillus Rhamnosus Powder
2
miyarisan (jp) / miyarisan
2
PureGG
2
spain (es) / bivos
2
spain (es) / kaleidon
2
spain (es) / ns florabiotic instant
2
spain (es) / suerobivos
2
reg’activ / immune & vitality
1.83
CustomProbiotics.com / L. Salivarius Probiotic Powder
1.67
miyarisan (jp) / miyarisan
907
enviromedica terraflora sbo probiotic
828.67
bio-botanical research / proflora4r restorative probiotic
730.25
perfect pass / perfect pass probiotic bacillus spore
730.25
CustomProbiotics.com / L. Plantarum Probiotic Powder
722.2
goodbelly drink
722.2
HLH BIOPHARMA(DE) / LACTOBACT ® LDL-CONTROL
722.2
jarrow formula / ideal bowel support® lp299v®
722.2
Metabolics / Lactobacillus Plantarum Powder
722.2
Prescript-Assist®/SBO Probiotic
694.5
Sun Wave Pharma/Bio Sun Instant
690.92

We also have the option of probiotics based on symptoms (adjusted for the microbiome). See Using Samples and Symptoms to Suggest Probiotics post. The data is shown below in decreasing weight order. The nice thing to see is the decrease in the weight of everyone. One totally disappeared (the sole enterococcus faecalis one). It is interesting to note that while above using only the microbiome and resulted in major shifts between samples, when the symptoms are combined the suggestions are very similar and actually reflect improvement of the microbiome.

Prior SampleLatest Sample
Prescript-Assist®/SBO Probiotic (34)
enviromedica terraflora sbo probiotic (4.4)
symbiopharm / symbioflor 1 (3.8)
klaire labs / biospora (3.7)
microbiome labs/ megasporebiotic (3.6)
Prescript-Assist®/SBO Probiotic (22.6)
enviromedica terraflora sbo probiotic (3.5)
perfect pass / perfect pass probiotic bacillus spore (2.9)
klaire labs / biospora (2.8)
microbiome labs/ megasporebiotic (2.7)

Suggestions

I am going to do my current practice of relying on consensus reports because they are now quick to generate. I will be doing a consensus from:

I will be including everything, since the reader is able to persuade his medical professional to prescribe.

Consensus Results

The following are my picks from the options presented. I provided some links to where it helped ME/CFS –i.e. the suggestions are reasonable

Items to reduce or avoid

Remember: These are suggestions, items that improve odds.

Prescription Suggestions

This is done using advance suggestions and flipping the selections:

The top suggestions were:

Secondary positive suggestions are:

Dangers of Filtering

The person tried using the ME/CFS filter and got very different results. This person has mild ME/CFS; the studies on the US National Library of Medicine are for ME/CFS are typically severe and matches a yard of criteria for inclusion in the study. It is often not safe to use there filters when you self-diagnosis or are mild/controlled.

Bacteria Selected using Expert Criteria

MethodFiltering By ME/CFSLatest
Use JasonH (15 Criteria)46
Use Medivere (54 Criteria)46
Use Metagenomics (59 Criteria)46
Use Nirvana/CosmosId (36 Criteria)46
 Use XenoGene (22 Criteria)46
 Standard Lab Ranges (+/- 2 Std Dev)36
Box Plot Whisker527
Kaltoft-Moltrup Normal Ranges1284
Percentile in top or bottom 10 %899

Adding filtering dropped the bacteria consider by a large amount (up to 92%!!).

My usual criteria has been to have at least 1-2 dozen bacteria. With the new consensus report, having a large number of bacteria seems to produce clearer results.

Bottom Line

Suggestions to be discussed with their medical probiotics

In terms of prescription (doing rotation with breaks between):

Supplements to try:

We saw improvements between the sample when this reader implemented some of the suggestions. Remember, the suggestions improves the odds, they do not guarantee nor is there any requirement or protocol to follow.

CFS / Myalgic Encephalomyelitis Microbiome Analysis

Reminder:

I am a computer scientist and a statistician. I am not licensed to practice medicine, and where I live has strict laws about ‘appearing to practice medicine’. What I can do for readers is to write a public blog (anonymous) from your data and back story as an education post on using the software and the statistics it produces. I cannot consult. The content should be reviewed by a medical professional before implementing.

Video walkthru of this post

Back Story

35yr old, female with ME of around 15 years, Coeliac and Crohn’s diagnosed in 2014 plus simple temporalobe seizures and endometriosis.

I have tested extremely extensively and most labs are generally normal with the exception of:

  • Prolactin- always slightly above high end of range
  • Lyme ELISA IgM positive but Blot negative (possibly cross-reactive with RF)
  • Rheumatoid factor – one point over upper range
  • LDH – consistently slightly above range
  • Aldolase – tested once, slightly above range
  • ALT – occasionally slightly above range
  • EBV – positive for past infection but never any evidence of reactivation
  • SIBO breath test positive for hydrogen only

I am really struggling with acne… I have been offered Lymecycline for the acne but don’t know if it’s worth the risk. I am currently on a 7-day course of Co-amoxiclav (amoxicillin + clavulanic acid) for an infected cyst (my Biome sample was taken before this).

I was able to control my crohn’s with an elemental diet, followed by strict paleo, then gradually reverting to a more relaxed diet. I did a course of oregano oil which was very harsh on the gut but it got rid of my constant bloating for the first time in my life (this came back and remains since reintroducing carbs). I’m 99.9% sure I’m on the autism spectrum. Interestingly, some of my autistic traits and my ME symptoms abate somewhat for a short period at the beginning of a cold virus (the first couple of days while fever is present). I had a similar temporary reaction to Sulforaphane.

My ME started while I was working full time, following glandular fever in 2006. The onset was characterised by ‘tired but wired’ and rolling PEM, finding it almost impossible to fall asleep until it was nearly time to get up and a complete inability to get into deep sleep. I reduced my working hours gradually but eventually gave up work fully in 2008. Even when ‘healthy’ I never had normal stamina, muscle mass and was really ready for bed by the end of the work day.

Possibly coinciding with my gastrointestinal diagnoses and subsequent avoidance of gluten, my symptoms calmed a bit from the ‘acute’ years, and I began to sleep a little better and get brief symptom-free interludes while at rest. Now, prolonged activity above baseline will lead to a return of the PEM and ‘tired but wired’ symptoms (inability to switch off nonsensical chattering thoughts at night leading to insomnia, feeling hot with chills, feverish, sweats, tossing and turning all night. These symptoms stop on rising but leave me extremely brain fogged from the sleep deprivation, and then repeat the next night. I also experience myalgia, headaches, orthostatic intolerance and strong need to lay horizontal throughout the day. I wake with heavy puffy face and eyelids most days. I go through periods of extreme dry mouth, worse on waking despite always hydrating well.

Even in my symptom-free-at-rest periods, I still struggle to get to sleep some nights, although I keep a strict routine 10pm-10am. I find it very difficult to get into the deeper stages of sleep almost all of the time. Even with all reasonable interventions and ear plugs I am easily startled awake by household sounds and there is usually activity from others from 4-5am onwards.

Microbiome Analysis

I am going to do three levels of Analysis. I will start with generic, then move on to diagnosis using US National Library of Medicine studies and ending with the latest refactor, using bacteria associated with symptoms discovered from uploads to this site.
The purpose of these analysis to get suggestions for the most probable bacteria causing issues.

Overall Health

I will not go step by step (see this post with video for how to do this) but do the following suggestion generation and then look at the consensus

Then I went to Advance Suggestion with Percentile: 15% and the following PubMed conditions (Remember that Display Level must be Intermediate or higher to see this option):

  • Acne – 3 bacteria
  • Crohn’s Disease – 24 bacteria
  • Celiac Disease – 14 bacteria
  • Chronic Fatigue Syndrome – 13 bacteria

Then I went to Symptom Associated to Bacteria (Citizen Science) and found the following applicable items:

For Official Diagnosis: Chronic Fatigue Syndrome (CFS/ME), most of the matched were at the Genus Level

The result is 40 bacteria added to our hand picked list.

Consensus Highlights

We have a lot of different suggestions over our 10 analysis, often more than 1000!

Suggestions to discuss with your medical professional

On the avoid list:

Also listed was gluten-free diet. I suspect the type of gluten may be significant.

KEGG Probiotics:

The usual one for ME/CFS are at the top (and were also listed in Safer or Safest Takes) :

For supplements:

  • beta-alanine – Percentile: 9.7
  • D-Ribose – Percentile: 4
  • Glycine – Percentile: 13.6
  • L-Cysteine – Percentile: 13.6
  • L-Threonine – Percentile: 6.5
  • Magnesium – Percentile: 0.1

Both D-Ribose and Magnesium are well studied supplements in a ME/CFS context (confirming predictions to clinical practice the items are linked to CFSRemission Blog).

Bottom Line

At this point I will stop for several reasons:

  • Purpose was to show the method
  • Person has brain fog often, so more notes may be counter productive
  • ME/CFS usually have restricted funds, so keeping the number of items low reduces frustrations over not being able to acquire.

A video will be added in the next few days

Questions And Answers

Q: I forgot to mention it, but I do have allergic rhinitis and high cholesterol (as listed under the detected conditions) so this is very accurate.

A: Although I see this often, it keeps surprising me about the accuracy of predictions!

Q: Interesting that it doesn’t pick up on any CFS-related bacteria at a species level, I wonder if this fluctuates and could possibly be because I was relatively low-symptom at the time of the sample, i.e. not in a PEM flare? 

A: You are very likely correct, it does fluctuates. Also, keep in mind that there are many subsets of ME/CFS, so this can be a little hit-and-miss.

Should I take Lymecycline?

A: This is a little complex, we have mixed results.

But when I tried a different antibiotic often prescribed for acne, it is all positive

I would suggest making a counter proposal to your medical professional of minocycline instead.

Q: I’d be interested in your opinion on IgY hyperimmune egg powder supplements for targeting gut pathogens

A: There are many retail products like this. What I found are some vet studies[36 listed here]. I found a list of clinical studies here. My general impression is that it is favorable. There is one word of caution, it appears similar to transfer factor — i.e. the IgY may be targeted to specific bacteria/infections only. Hence, my advice would be to buy just one unit of it, if no response, change to a different brand when you finish it. Remember my motto: Rotate, rotate, rotate….