Missing Vitamins, Minerals suggestions

Question:

Quick question—I noticed, for my BiomeSight-via-Ombre sample, that I’m not getting Vitamins, Minerals and similar suggestions. I used to get them on this sample. This only happens when I set the “Everything” option.

Anything I might be doing wrong? I’m generating the suggestions with the KM, Box Plot whisper, and Standard Lab Ranges. Avoiding Special Studies per your recent advice.

Answer: No Reproduction

I did a video to show what I did and the results.

Long time ME/CFS

Hi I’m a 15 year CFS sufferer with severe GI / neuro problems.  I got my second Thryve results recently.  They look really quite normal to me and it says I have significant diversity.  Is there any help / analysis you could provide to help me narrow down if there’s something actionable?  I’m not sure how much capacity you have for that, but it doesn’t hurt to ask.

  And unfortunately have been sick for longer.  Got sick at age 25 with an infection (low grade fever for months), lost 30 pounds, had vision problems, headaches, fatigue and so on.  I was able to work four years in this state but eventually I had much worsening neuro and vision symptoms and was unable to work.  I developed POTS a couple years later and at times was using a walker to get to the bathroom and was bedbound.  I’ve had some episodes of vision loss that are very strokelike in that they debilitated me cognitively and visually for long afterwards (the vision loss itself resolves after some minutes or hours).

I want to emphasize the visual and cognitive impairment are totally debilitating.  I can barely read anything or reliably focus my eyes on anything, and I went from a previously extremely high functioning person to feeling drugged, barely here 24/7.  I have severe eye pain all the time.

So I’ve been sick for really my whole adult life, to varying degrees.  Primary debilitation is visual and cognitive but I have severe physical fatigue, POTS, am 30 pounds underweight, have been diagnosed with gastroparesis years back I just can’t keep the pounds on.  Also it is notable food makes me feel TERRIBLE. Right away I can feel stupid and drugged from it, but also 2-5 hours later is when I ache everywhere and get tired and non-functional.  The 2-5 hours I’m presuming is from some dysbiosis but right away is a little more puzzling.

I clearly have such bad digestion that it is not hard to imagine it is perpetuating my brain / eye / POTS symptoms.  I’ve tried everything under the sun, mainstream and holistic and nothing that is supposed to help the gut helps.  I think fasting gives me some relief but is not practical for someone so underweight.

My first thryve was on January 13, 2020.

My most recent thryve (now ombre) was October 2, 2022.

In between the two times I’ve cycled through several gut protocols, such as taking s boulardii, soil probiotics, bifidobacteria, sourkraut, and polyphenols.  Other times I tried a more killing oriented protocol with oregano oil, berberine, and once based on a stool test a prescription antifungal (sporonox).  I eat a very restricted diet and seem to react to pretty much every food, but I have cycled through different foods in the last couple years.  I’ve tried prebiotics like PHGG and lactulose recently and are finding at least in the short term I am losing weight and have worse neuro symptoms.

My digestion and overall symptoms have not really changed between the two times.  ombre says I have a quite high microbial diversity score which is surprising because I have a massive history of antibiotics.

The request

First Look at the sample

Comparing the samples, I see a much lower quality report (2.5) in 2020. It was interesting to see

  • Bacteria Over numbers drop despite more bacteria is latest sample
  • Bacteria Under numbers grew — which may be due to a better quality of sample (more bacteria)
  • Two of my usual measures showed improvement (despite more bacteria) — Outside Lab Range, Outside Box-Plot-Whiskers while the last one showed an increase which was a smaller percentage than the increase of bacteria reported.
    • My impression is that objectively he appears better than in 2020.
CriteriaJan-20Sep-22
Lab Read Quality2.58.5
Bacteria Reported By Lab442656
Bacteria Over 99%ile102
Bacteria Over 95%ile4510
Bacteria Over 90%ile8823
Bacteria Under 10%ile54154
Bacteria Under 5%ile2194
Bacteria Under 1%ile619
Lab: Thryve
Rarely Seen 1%57
Rarely Seen 5%2837
Pathogens3232
Outside Range from JasonH66
Outside Range from Medivere1616
Outside Range from Metagenomics1010
Outside Range from MyBioma1313
Outside Range from Nirvana/CosmosId1818
Outside Range from XenoGene99
Outside Lab Range (+/- 1.96SD)275
Outside Box-Plot-Whiskers12451
Outside Kaltoft-Moldrup183239
Condition Est. Over 99%ile00
Condition Est. Over 95%ile10
Condition Est. Over 90%ile40
Enzymes Over 99%ile12190
Enzymes Over 95%ile208516
Enzymes Over 90%ile457585
Enzymes Under 10%ile59265
Enzymes Under 5%ile20154
Enzymes Under 1%ile220
Compounds Over 99%ile7324
Compounds Over 95%ile264101
Compounds Over 90%ile368172
Compounds Under 10%ile297265
Compounds Under 5%ile225223
Compounds Under 1%ile62165

In terms of bacteria distribution (not “diversity”). we see an abundance of domineering bacteria (90-99) in the earlier sample which flipped to proliferation of weak bacteria (0-9). Have tons of small amounts of bacteria at low levels should result in a good diversity. The over-representation of these nominal bacteria is a concern to me.

His attempts to change was successful. Ideally we can help more change in the desired direction.

Approach

Using PubMed data, nothing stands out and we have a very short list. This simply means that there is not a good match to the conditions reported there. In terms of Dr. Jason Hawrelak Recommendations we are at 89%ile, so generally good. The main items missing the goals by his criteria are: Faecalibacterium prausnitzii, Lactobacillus, Bifidobacerium and Akkermansia.

Given no strong pattern to match against, I will build a consensus from Lab RangeBox-Plot-Whiskers, Kaltoft-Moldrup and Dr. Jason Hawrelak Recommendations

Consensus – similar to a pattern common with ME/CFS patients

Cross validation to the literature on the above (i.e. seeing if any has been documented to help ME/CFS). Since neurological issues were called out (and I had just done another sample with this recommendation, a few more for Hesperidin)

So all of the top suggestions appear to have documented benefits for various subsets of ME/CFS. I use the term subsets because, while similar in some symptoms, there may be a lot of differences.

We also have the simplified suggestions (with dosages). This list is intended for the brain fog person.

Looking at this list, we see that he should consider using some of the probiotics he cited in his history: bacillus subtilis, bacillus clausii, bifidobacterium (animalis)lactis, bifidobacterium breve bifidobacterium infantis. We also have 3 lactobacillus which seems to often appear with ME/CFS samples: lactobacillus casei, lactobacillus gasseri and lactobacillus salivarius.

In terms of prebiotics, only chitosan was a positive. Selenium shows up as a strong recommended supplement. See the above download for more details.

Very atypically, KEGG probiotics reports very low recommendation values with E.Coli NOT being on the top of the list. I would keep to the above probiotics and ignore the KEGG list because of the low values.

Going over to the last, experimental, modelled food suggestions, Barley was the sole take. In terms of the consensus report, it’s a toss up with different variation being good to take or to avoid. Checking oats by itself, it’s a significant negative so I would exclude the last item below and suggests barley be considered.

Bottom Line

The top suggestions can all be verified in medical literature as helping ME/CFS and the suggestions are based on this individual’s microbiome — hence patient (and not study group) specific. Hopefully he will try them and in 3-4 months do another sample so we can evaluate the change (for better or worse — I want to learn, not be right).

Because of the weight issue, I would suggest trying Pendulum, the akkermansia probiotic. I noticed that it resulted in weight loss for me and recall that is also reported in the literature.

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 appears to 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.

I use modelling and various mathematical technique to estimate forecasts when there is no hard data available.

Blood Status influenced by the microbiome?

The information below comes from Integrated analysis of gut microbiome and host immune responses in COVID-19 [2022]. While the data comes from COVID patients, there is a good chance that it may apply to other conditions. The items below are for the strongest p-values (most likely). My intent is to add all items with a value with a p Value of 0.05 or less as an experimental page, before creating the page I hope people will find similar studies that can be combined with this data. Please add as comments.

Gut_microbesBlood_clinical_featuresCorrelationPvalue
Coprococcus_comesCD8_counts0.731735491.95E-06
Coprococcus_comesCD3_counts0.7142582574.41E-06
Coprococcus_comesLymphocytes_counts0.6497874555.71E-05
Coprococcus_comesCD45_counts0.6470093386.29E-05
Roseburia_intestinalisCD8_counts0.636696048.94E-05
Roseburia_intestinalisCD3_counts0.6198607290.00015457
Roseburia_intestinalisCD45_counts0.6117476250.000199038
Streptococcus_oralisEosinophil_counts0.6030561980.000258997
Gut_microbesOrgan_damage_related_factorsCorrelationPvalue
Akkermansia_muciniphilaCreatine_kinase_isoenzymes0.8895227041.00E-11
Bacteroides_cellulosilyticusCreatine_kinase_isoenzymes0.881775232.63E-11
Streptococcus_oralisGamma_glutamyltransferase0.7884431868.39E-08
Akkermansia_muciniphilaAspartate_Transaminase0.7843689081.08E-07
Bacteroides_cellulosilyticusAspartate_Transaminase0.7660755183.22E-07
Gut_microbesCytokinesCorrelationPvalue
Ruminococcus_gnavusIL170.5134319660.002652723
Klebsiella_pneumoniaeIFNG0.4848013010.004922183
Klebsiella_pneumoniaeIL100.4315828180.01364772
Lachnospira_eligensIL20.3930080180.026072229
Gut_microbesCoagulation_factorsCorrelationPvalue
Enterococcus_duransAPTT0.3582169370.044101648
Enterococcus_faeciumAPTT0.3571526760.044780215
APTT is activated partial thromboplastin time, the time to form blood clots

Xenogene: From Sweet Report to Bad Report

I started Microbiome Prescription site using data uploads from ubiome, a firm that was founded by a crowdfunding campaign, went to venture capitalists, and went unethical due to pressure from venture capitalists and died. I received over 800 samples processed by ubiome.

Readers started to request the microbiome reports to be processed on the Microbiome Prescription site and I started adding them according to constraints of the reports available. BiomeSight.com, a UK firm, has been the most cooperative. We worked together to allow automatic transfers directly from their web site to the Microbiome Prescription site by using a API.

Xenogene | Metagenómica y Biología Molecular Reports were shared to me. I found that I could do an accurate extract from one of the reports they made available to users. The result was that they became the most comprehensive report as see by the statistics below

There were few uploads because of their higher costs. The report that I used is shown below.

They Changed Their Report

Recently I have had two people trying to upload their reports. The report was different than the above. I asked them to contact Xenogene to get the above; they were not successful. I examined their reports (they were several years apart), and found two different formats, as shown below:

While both give the same information, the structure of the page was different. The report do not give the hierarchy, for example, Eubacteriaceae was found in neither report. I looked for Blautia and could find species and strains — but no total, so you cannot apply Dr Jason Hawrelak criteria.

Summing up all of the species and strains under Blautia does not give a correct total, in some cases the Blautia total will be 2x higher. Why, because many strains and species has not received names and / or “fingerprints”.

Example of the synthesis to higher levels… Issues at the species level and below can be identified

Bottom line: I no longer recommend this lab

Despite these issues, I have updated the import to support both of the above PDF formats and synthesize all of the missing layers of the bacteria hierarchy. The new import should be on line by November 13th.

WARNING: the genus level and above may often be low because of the total synthesis.

I did extract their recommended ranges and added it as an option:

Citizen Science Action

I would suggest emailing them and asking them if they make a CSV file available of the results (including the bacteria NCBI taxon number), if so, can you get a sample. If you do not get a positive results, do a return email asking you to be informed if they change and indicating that you are going to use Ombre or Biomesight instead…… The risk of loosing customers can often change business practice.

Microbiome Activism Please!!

This applies not only to Xenogene but

and also these lacking NCBI taxon numbers

ME/CFS After Severe Stress

Backstory

I emailed about six months ago with questions. Since then I’ve attempted an evaluation of my microbiome’s needs through a thorough look at your site’s AI suggestions. I attempted to implement some of those, with my primary care’s approval. I didn’t have much luck and I was looking to have another go at it, with a fresh Ombre analysis. I’m formally requesting a review for an educational post. Before I jump back into trying the AI’s suggestions again, I thought it would be foolish if I didn’t seek out the assistance of the one who designed it. I understand there are others in line and you may decline the request, but I appreciate that you are offering this to people. Hope is such a necessary lifeline with CFS. 

It feels a little odd to be giving such detailed information about myself without having a firm “go ahead” from you. From what I understand though, you want all the info before you’ll consider the request. I’ll attempt to make it brief. I have also uploaded my symptoms to the website. I consent to your use of my information.

  • Symptoms
    • Fatigue
    • Exaggerated loss of muscle strength with exertion
    • Brain fog
    • Trouble reading and comprehending
    • Post exertional malaise
    • Constipation
    • Panic Attacks

-Intolerance to any probiotics, *DAIRY*, caffeine, alcohol, refined sugars, and a growing list of fruits and vegetables.

-Whatever herbs I try there is almost always an initial benefit, but then things go back to the way they were. (Possible bacterial adaptation?)

  • Diagnosed
    • “Chronic Lyme”
    • ME/CFS
    • IBS-C
    • Panic Attacks
    • Depression

~ Backstory ~

Dec 2012 – I had been working multiple full time jobs while eating very poorly. Essentially fasting, and what I did eat was high carb, low nutrient foods. No fruits, vegetables, or other nutrient rich items. I felt something snap in me in an instant. I felt panicky and went and ate a large meal immediately. From that moment on I’ve suffered from CFS. The most prominent features being fatigue, exaggerated loss of muscle strength with exertion, brain fog, trouble reading and comprehending, post exertional malaise, and constipation. My symptoms were the most exaggerated at that time, although recently they have started to get back to that point in time. Examples: I would eat a carb rich food like pasta and 30 minutes later I would literally be on the floor in a quasi lucid state; Two and a half weeks without a BM. My primary care at the time put me on antidepressants and thyroid medications, which did nothing for me.

March 2016 – I started to see an integrative medicine MD who thought that I had reactivated Lyme. He reasoned that it was dormant in my system from when I had it as a 5-6 year old, and that the stress allowed it to manifest itself again. I was on an absurd amount of supplements and various antibiotics. I found initial improvement that I felt stopped my decline and helped with some symptoms, but didn’t solve the CFS. The one drug that I felt the best on was Tinidazole. I stopped seeing him in 2017.

July 2017 – I stopped working as my symptoms had continued to get worse over the years. I started taking care of my sister who was diagnosed with terminal brain cancer. She died in 2019.

July 2018 – Started to see a new primary care. He confirmed the CFS diagnosis but refuses to help in any way. He encourages me to seek solutions on my own however.

Dec 2018 – Started to see another Lyme specialist who told me about the herbalist Stephen Buhner. I bought his book and attempted a slew of his proscribed herbs over the course of a year or two, with little benefit. He also put me back on doxycycline for 6-12 months. It did help but just by taking the edge off of my symptoms.

Fall 2019 – I started to develop panic attacks. It was clear to me that stress made them worse but that it was primarily an issue stemming from a physical problem, rather than an emotional one. This was evinced by the fact that certain foods could manifest them. I felt that whatever my problems were, they were physical and were slowing progressing.

Summer 2021 – I started looking into gut health as a cause of CFS. I started the Wahl’s diet and found some improvement through that. It afforded me enough strength to go back to work for six months. I never entered fully onto the diet as it was prohibitively expensive, but I did keep some of the foods that helped.

2021 – I started to see a gastrointestinal dr. who was absolutely no help. He diagnosed me with IBS-C but didn’t have any answers or solutions. He did proscribe Amoxicillin, which I declined to take as I was not sure if it would help or hurt my gut bacteria.

April 2022 – I found your website, uploaded an Ombre test, and attempted some of the suggested herbs. I found initial benefits from cinnamon but any long-term attempt at any of the herbs is really a trial (and I’m not one to back down from a fight or a stranger to discomfort). I continued on some of them until I thought there might actually be a chance of dying from it. I just couldn’t tell if it was herxing or hurting.

Spring 2022 – Developed food sensitivities, primarily to dairy. Dairy gives me intense psychological issues. The best I can describe them is that they are like racing thoughts accompanied by the feeling that my head will explode and there is no way to escape. Food that once helped, like carrots and berries, now make my intestines feel like overinflated balloons: a lot of pain. 

August-October 2022 – I started to care for my mother who was diagnosed with terminal stomach cancer. She died and the stress of it has amplified my already mounting symptoms to a fevered pitch. It almost feels like when things started back in 2012.

This story is unfortunately very typical for many people. My wish is that Microbiome Prescription will be able to help. I do not have “the cure”; what is generated are suggestions (many — so pick and choose what works for you), items modelled to have better than random impact on the microbiome.

First Look at the sample

We have two Ombre samples on the account:

  • May 2,2022
  • Oct 18,2022

With two samples from the same lab, my first step is typically to compare them. I omitted the KEGG data which was not illustrative of changes.

CriteriaOld SampleNew Sample
Lab Read Quality4.25.6
Bacteria Reported By Lab561677
Bacteria Over 99%ile27
Bacteria Over 95%ile1821
Bacteria Over 90%ile3843
Bacteria Under 10%ile92121
Bacteria Under 5%ile3762
Bacteria Under 1%ile311
Lab: Thryve
Rarely Seen 1%58
Rarely Seen 5%2354
Pathogens4030
Outside Range from JasonH33
Outside Range from Medivere1414
Outside Range from Metagenomics99
Outside Range from MyBioma1212
Outside Range from Nirvana/CosmosId2121
Outside Range from XenoGene88
Outside Lab Range (+/- 1.96SD)940
Outside Box-Plot-Whiskers67128
Outside Kaltoft-Moldrup136244
Condition Est. Over 99%ile00
Condition Est. Over 95%ile00
Condition Est. Over 90%ile01

My read is that between the samples, the person has gotten worse. Why?

  • Outside Lab Range (+/- 1.96SD), Outside Box-Plot-Whiskers, Outside Kaltoft-Moldrup all have very significant increases,
    • This is also reflected in Bacteria Over ??%ile and Under
  • Not having any strong matches to (PubMed Studies) Conditions is unusual. It suggests that the compounding of issues results in the microbiome not falling into any established “box”.

We see that also with the distributions, a massive surge of under-represented bacteria (0-9)

While he attempted suggestions after the first sample, we see a mountain of microbiome changing events also occurred (especially stress which, for me, has been very significant cause of my own historic dysbiosis). Whether the suggestions helped or hurt cannot be determined.

Approach

Building a consensus from Lab Range, Box-Plot-Whiskers and Kaltoft-Moldrup seems the best approach.

Early Sample

From the consensus we see a list which agrees with what is often reported as helping ME/CFS from the earlier sample.

From Earlier Sample

Some illustrations from the literature of the suggestions

The person cited issues with dairy. In the consensus it was listed as an avoid. Also listed was also: galactose (milk sugar), high saturated milk fat diet, milk-derived saturated,fat.

For #1 suggestion: Hesperidin (polyphenol) [available as a supplement] we see the following studies:

What I did above is called, cross-validation. This means checking if the suggestions generated by the model agrees with clinical experience. It does. This implies that items not seen in studies (like a grapefruit for breakfast) seems likely to have positive effects.

Cross validation is always a good step after getting suggestions. The suggestions using this trio of methods to select will mostly be good — but odd cases may produce poor results.

Example of how to do it

Latest Sample

Given the stress etc. I know that the microbiome will shift and may not be so easy to cross-validate. We see many of the same things, they have just rearrange themselves.

As a FYI, Dairy was 10x more negative in this sample, and other dairy items similarly MORE stronger to avoid: Whole Milk, high saturated milk fat diet, milk-derived saturated,fat. In agreement with dairy issues.

Two Other versions of Suggestions

We have the simplified suggestions (shown above) with the to-take probiotics being:

  • bifidobacterium (animalis) lactis
  • lactobacillus gasseri
  • bacillus coagulans (with bacillus subtilis being a very strong avoid).
  • KEGG suggested Escherichia coli Probiotics — which is to be expected from ME/CFS. A low level of Escherichia coli has been reported in the 1999 Australian Conference papers.

My suggestion would be ONLY bifidobacterium (animalis) lactis (Custom Probiotics has it available as a single species without additives) and E.Coli (i.e. Symbioflor-2 )

The last version of suggestions is a food list derived from flavonoids etc in food. It is an experimental exploration (so a grain of caution is suggested).

The only thing that was positive was Barley which is on the avoid list. So nothing (safe) useful from this experimental method.

As a FYI, I checked for items that are adaptogens (helps with stress) and the following were on the to-take list.

Note on the numbers on various lists

The suggestions often have numbers beside them. The numbers are relative numbers for things in the same list. In simpler words:

  • One in Metric, – meters
  • One is Imperial/American, miles
  • One is Roman, league
  • One is nautical, knots
  • One is astronautical – parsec

They cannot be compared to each other. The goal of each list is find the best given the approach.

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 appears to 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.

I use modelling and various mathematical technique to estimate forecasts when there is no hard data available.

An update on results of prior analysis

This is a follow up of several prior posts

This person did his tests using OmbreLabs.com and then transfer the data to biomesight.com.

I did the special studies for a couple months taking symbio, florastor, GOS,Arabox., d ribose, pea fiber, etc. 

Feel in general more energized, specially after the round of florastor which I had done just a four days then tested at the time so impact probably won’t fully show in this test. 
Where to go from here? Drop special studies focus  or stay the course?

Why Follow Up Posts are important

The first item is simple, does the model and suggestion appear to work. Everything is theoretically computed, not based on clinical practice or clinical studies. The second item is that these posts encourages people to try suggestions, or to do “self-serve” with the site.

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 appears to 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.

Comparisons between Samples

We will start by adding new columns for the latest sample. The person measured with Ombre and then transferred data to Biomesight to get a second interpretation of the raw digital data.

CriteriaBS 6/6BS 7/19BS 11/22OL 6/6O 7/19O 11/22
Lab Read Quality2.15.44.22.15.44.2
Bacteria Reported By Lab280497468365628473
Bacteria Over 99%ile270561
Bacteria Over 95%ile2431227249
Bacteria Over 90%ile495812495121
Bacteria Under 10%ile1762187186087
Bacteria Under 5%ile53090102846
Bacteria Under 1%ile01322172
Rarely Seen 1%040090
Rarely Seen 5%418158409
Pathogens152539192833
Outside Range from JasonH449729
Outside Range from Medivere171720161620
Outside Range from Metagenomics777777
Outside Range from MyBioma9910141410
Outside Range from Nirvana/CosmosId222222232322
Outside Range from XenoGene6610111110
Outside Lab Range (+/- 1.96SD)613210142
Outside Box-Plot-Whiskers708429646125
Outside Kaltoft-Moldrup701137011218291
Condition Est. Over 99%ile110000
Condition Est. Over 95%ile240000
Condition Est. Over 90%ile560220
Enzymes Over 99%ile310113155
Enzymes Over 95%ile4632166982147
Enzymes Over 90%ile9051103155411405
Enzymes Under 10%ile10221935455138169
Enzymes Under 5%ile45132154226778
Enzymes Under 1%ile64729520
Compounds Over 99%ile972910412619
Compounds Over 95%ile567623338539789
Compounds Over 90%ile292313347533548118
Compounds Under 10%ile72125264183248133
Compounds Under 5%ile3964163109127100
Compounds Under 1%ile52141161742
Note: I just cut and pasted from “Multiple Samples” tab to Excel to make the above table.

What do I see above?

  • Sample Quality are the same (expected from using the same FASTQ file)
  • Rare and very high bacteria have a significant improvement
  • All of the statistical out-of-range measures(Std Dev, Box-Plot, K/M) reduced the count significantly.
  • Most of the expert suggested ranges increased.
  • Condition profiles dropped to zero.
  • We see the fragileness of some measures to the software being used to interpret the raw data.
    • Enzymes Overone dropped from prior and the other increased from the prior

My general opinion is that the person has improved objectively. The algorithm explicit goal is to reduce all of the statistical out-of-range measures. Ideally, it will also “fix” the person but that is more complex, we lack sufficient knowledge to hand pick the bacteria. We can get associations to specific bacteria — association is NOT causality often (despite many politicians claiming such!).

Going Forward

KEGG Computed Probiotics

Both labs resulted in the same priority: Escherichia coli at the top, the soil based mixtures, then Bacillus subtilis (I personally prefer to get it “au natural”, i.e. in the traditional Japanese Soy based food, Natto).

BBC Japan’s most polarising superfood?

Special Studies Numbers

I am going to skip them, mainly because the results are erratic until I get a better understanding of this. See Caution: Special Studies Suggestions.

There is a possibility of both being right. Right meaning shifting from the current dysfunctional equilibrium. This could be visualize as shown below. I am seeking understanding and building different approaches. Each approach could work for some (but not others). Too many factors for certainity.

Going forward

I am building a consensus report from the items marked 2 above using the Special Studies. The list is similar to other people with ME/CFS. We see 2 E.Coli probiotics (symbioflor 2 e.coli probiotics, colinfant e.coli probiotics) at the top with d-ribose (a sugar used by E.Coli). This is then followed by the earth based probiotics( General Biotics Equilibrium, Prescript Assist (Original Formula), Prescript Assist (2018 Formula)).

For Consensus building, I am going to use the three statistical selectors with both Ombre and BiomeSight:

Then we will do an uber-consensus (combining the consensus from each)

The suggestions look very typical for ME/CFS persons. I attached the Simplified Suggestions

The probiotics suggested are

  • akkermansia muciniphila
  • bacillus clausii
  • bifidobacterium (animalis)lactis
  • bifidobacterium breve
  • enterococcus faecium
  • lactobacillus brevis
  • lactobacillus bulgaricus
  • lactobacillus casei
  • lactobacillus paracasei
  • lactobacillus rhamnosus
  • lactobacillus salivarius
  • pediococcus acidilactici

I have marked the lactobacillus to indicate that they do not play well with E.Coli probiotics. Thus, should be in an alternative probiotic cycle.

We see by individual fibers, that the separate suggestion of a low fiber diet

Fiber suggestions

The New Boy on the Block: Food Suggestions

See New Suggestions Page — Food Centric. This was trying to mine the available data more to get practical suggestions.

  • Flavonoids: Only Barley was a positive (for Ombre) , it was not on Biomesight list
  • Food Contents: Again, only Ombre had positive suggestions: Brazil Nuts and Olive Oil. Biomesight data disagreed on the Brazil Nuts

Why so few? Why labs contradict? This comes down to two key challenges: Different interpretation of the bacteria from the digital data; a low volume of studies on the substances we are using to build food suggestions. Also, the suggestions are based on some of the contents of the food; there are other parts of the food that will have other effects. This is why direct food, herb and spice studies are best. Every food is a complex mixture of chemicals. Some may help, some may hurt. Care must be taken to avoid the simplistic logic that “Super Breakfast Food contains barley, thus it is good/healthy to eat!” Ignoring the 10 grams of sugar in this product.

Thus, these suggestions should be taken with a grain of salt. They are better than random choices, but far short of what we would ideally like.

Bottom Line

I ran some of the Special Studies suggestions and did a download of simplified consensus. Between approaches, we had agreement on taking:

  • Probiotics:
    • akkermansia muciniphila
    • bifidobacterium (animalis)lactis
    • lactobacillus salivarius
    • saccharomyces boulardii 
  • Other
    • Vitamin K2
    • Calcium
    • Echinacea
    • Omega-3 fatty acids
    • Pomegranate
    • Rutin
    • Tea Tree oil

As well as agreement on avoiding

  • fructooligosaccharides (FOS)
  • jerusalem artichoke
  • Flaxseed
  • Vitamin B2 Riboflavin

“This is too complicated” is what I can hear some people saying. This analysis digs into the nature of the data which is really not needed for most people. I am trying to get better understanding. It looks at some of alternative methods of getting suggestions. It is likely of interest to those treating microbiome dysfunctions as it illustrates many of the challenges in interpreting.

For most people, the best process stays the same:

Why is consensus important? Simple, we have very incomplete data and also have limited accuracy with the microbiome tests. Going the consensus approach is similar to using a Monte Carlo Simulation, an appropriate approach to deal with complex processes with many parameters that are fuzzy that produces better results.

Inaccurate Enterobacteriaceae/Escherichia/Shigella Reports

This post came out of a Facebook dialog with someone reporting they are taking Symbioflor-2 and not seeing any changes in test results.

This study says it well: “16S rRNA sequencing is not diagnostic for Enterobacteriaceae or Escherichia/Shigella“. Rethinking gut microbiome residency and the Enterobacteriaceae in healthy human adults, 2019

The numbers reported on most tests for these bacteria are extremely questionable. The one exception is Xenogene (based in Spain). This can be seen on these summary pages. These bacteria are grossly under reported on 16s tests.

What does this mean for manipulation? If you take Symbioflor-2 or Mutaflor, you may not see any changes in your tests (or they may become worse), when in reality they have taken up residency and are increasing. Either you go and do tests with Xenogene; or you use subjective measurements. My subjective measurement from Mutaflor was a massive severe herx for the first two weeks.

Some other recommended readings:

A probiotic care package to a mother in India with an UTI

I got messages as shown below, and thought that I should share my thinking and suggestions.

Hi Ken I needed some help from you on some inputs. My mom she is 63 years old and from past few months she is getting recurrent urinary tract infections and she is been taking antibiotics. She takes one antibiotic for Ecoli UTI and next time urine culture shows Pseudomonas and again she takes another antibiotic and another infection starts.

Do you know any good probiotics which are live and multi strains?

I was thinking about sending my mom suffering with UTIs the below 2

Renew Life Women’s Care Probiotic, 90 Billion CFU Per Capsule, 12 Strains, Shelf Stable Probiotic, Gluten, Dairy and Soy Free, 30 Capsules

Garden of Life Dr. Formulated Probiotics Urinary Tract+ – Acidophilus Probiotic Supports Urinary Tract Health, Digestive Balance – Gluten, Dairy, and Soy-Free – 60 Vegetarian Capsules

Please share your thoughts if they are live probiotics and can be helpful ?

My Response

See this page for RESEARCHED probiotics available retail (somewhere). You may wish to scan each study for effectiveness etc

You can also just change the search word for specific things. For example, this shortens the list to UTI + E.Coli

Almost all retail probiotics are live, I believe that you actually means persist. I have a page on those,
https://blog.microbiomeprescription.com/probiotics-need-to-know-basics/studies-on-probiotic-persistence/

So you need to find ones that have been documented to help, and also persists, and last — be able to get fast delivery so they can be sent to India with a friend that is travelling there.

The results are shown below:

Probiotic SpeciesResearchedPersistsOn Amazon
Lactobacillus rhamnosus GG (Culturelle)YesYesLink
Enterogermina YesYesLink
B. longum BB536YesYesLink

Other items that are Researched and Persists BUT not available in this time frame

The ones that you suggest may work — but there is no evidence (peer reviewed studies) for them being either effective for UTI or persists. The three above have the best odds of doing the correction. Enterogermina is antibiotic resistant.

Quantity

I would suggest at least a 90 day supply for all of the above. 30 days may be sufficient, but given the challenges of re-supply, it is likely better to be safe.

ME/CFS Person in Japan or not?

This email arrived and contributed in two changes:

  • Warning on using Special Studies — suggestions can be erratic and should not be used if they conflict with the usual consensus building algorithms.
  • Adding Modelled Food Suggestions — this should also partially address some challenges doing suggestions in Japan

Back Story

Love your work, I have read many of your posts on CFSremission, and based on that and my own research I think your microbiome-based view of ME/CFS is generally correct.

I have been suffering from cfs since 2009, I did a study abroad in South Korea and had a weird fever there, after that I got tired easily, often felt light-headed, head felt hot, but I was able to mostly live a normal life and actually spent a lot of time in the gym. (I think this supports the microbiome theory, my diet changed radically when I went to Korea)

I dealt with the fatigue with regular consumption of coffee/tea throughout the day, often going out drinking at night. I also used to lift weights in the gym almost every day. Full body lifts like squats, deadlifts, etc. During this time I drank about a quart of milk a day as part of my bodybuilding routine. My sleep always seemed unrefreshing.

Then in late 2019 I got sick with a EBV/Mono-type illness, swollen lymph nodes and tonsils, crushing fatigue, sore throat, that lasted a month. Sore throat resolved, but the tonsils were still a bit swollen and the lymph nodes got smaller but seemed to be permanently hard. I thought I might have thyroid issues or cancer, but multiple screenings ruled that out. 

I tried multiple times to go back to the gym, but my workouts were poor and I got hit with what I now understand to be PEM the next day. Eventually I had to stop trying to exercise. I’ve tried various supplements such as methyl-b12, doses of tumeric or curcumin, too many to count, then I discovered your website. I think it lines up with my experience and is a good model to explain the so-called “anomalous” way that some treatments work for some CFS sufferers and not for others.

So I am writing this email to you now hoping I can get some insight. I have read your blog posts about other CFS sufferers analyzing their samples, so I hope you could take a look at mine as well. Feel free to use this or parts of it as a blog post, but don’t use my name or email address obviously. 

Some background, I had to get a sample manually added from a lab here in japan, based on those suggestions I took two rounds of miyarisan, (I live in Japan, so it was the most easily obtained of the probiotics suggested) as well as added lots of inulin, oats, whole grains etc. to my diet. Similar to some of your other posts, including the suggestions to avoid Vitamin B supplements (the greedy bacteria taking the B-vitamins!) But, I feel like it made me worse. These days my legs are very heavy and tired. 

I had another sample taken between the two rounds of miyarisan which i sent to Biomesight (a much better choice.) It took over a month for the results to get back. When they came back, it suggested a totally different course, putting miyarisan and inulin into the strong-avoid category! With the inulin+oats+miyarisan diet, I am more tired and my libido dropped a lot.

So I made a new analysis based on the national and special studies for unrefreshing sleep, ME/CFS without IBS, cold intolerance, general fatigue, etc.

1. As attached, it suggests “alcoholic beverages” pretty high. How should I interpret this? Beer? Wine? Vodka shots every evening? Is there more context for this?

2. Not many foods with any strong suggestions, what can I eat realistically (here in Japan) off this list of suggestions? It suggests a milk diet, but whole milk is not suggested? Seems to have a lot of contradictory suggestions.

3. I decided to go with national + special studies, but the “general consensus” is totally different. I assume the studies are better for my condition?

Feel free to look at the data of both of my samples, or offer a different way of getting a consensus, I really need some guidance here!

Regards,

From a reader (with permission to post)

Initial Impressions

The Key Problem with Suggestions is the picking of bacteria

Suggestions are based on several main factors:

  • The bacteria you decide to alter (i.e. increase or decrease)
  • The importance of each (sometimes called weight) when there is a trade off
  • What substances has had any research. This is a nightmare – between contradictory results, small sample sizes, study done in the context of a specific diseases, etc. This is why I use fuzzy logic.

With the above stated, I walked thru this sample trying to first improve the bacteria selected (using my experience and statistical understanding), and then looking at the suggestions they generate.

This issue can be compounded with the depth of bacteria reported. “The disease is in the small details”. This is why more detailed and comprehensive (i.e. number of bacteria types reported) tests are a better starting point.

Contradictory Suggestions root issue

Facts in the database are based on what is specified in the study. A simple example: one study may use turmeric and a different study used curcumin. Curcumin(diferuloylmethane) is a main component of turmeric, but it also contains two other compounds demethoxycurcumin, and bisdemethoxycurcumin. In addition, volatile oils (tumerone, atlantone, and zingiberene) [Antiinflammatory Herbal Supplements, 2019]. The studies may result in a bacteria increasing in one and decreasing in the other. Both are right! It is the additional components that are significant. The worst case of “fuzziness” is with anything that has the word “diet”. Many people offering advice will deem them to be the same to simplify the facts that they need to remember; Dr. A.I. does not need to simplify — but that comes at a cost of confusion when things seem similar at a high level to the user. Another example: lactate, lactose, versus milk.

Analysis

Going to the My Profile / Health Analysis page, we see the two items that where he is at highest percentile (98%ile and 99%ile) are related and would agree with unrefreshing sleep.

  • Sleep Apnea
  • Insomnia

ADHD is high, but that seems common with ME/CFS. Dr. Jason Hawrelak Recommendations come in at the 89%ile. Going over to special studies, we see a lot of matches. The matches are not predictive — there are other factors (like DNA/SNP) before symptoms appear. They indicate simply increased risk.

Strategy to build Consensus

The two PubMed profiles above, Standard Lab Ranges (+/- 2 Std Dev),  Box Plot Whisker, and Kaltoft-Moltrup Normal Ranges gives 5 sets of suggestions. This will be my base set. I will also look at some special studies results (comparing those suggestions to

Simplified Suggestions

The majority of probiotics are to be avoided (not unusual for ME/CFS). The top suggestion was lactobacillus casei which is an easy one to get in Japan. The well studied one is sold as Yakult. The next ones are: lactobacillus gasseri, bifidobacterium breve. With most of the probiotics being negatives, you do not want to get them in probiotic mixtures.

Most pre-biotics are to be avoided.

In terms of vitamins, we see most of the B-vitamins are suggested (this is seen in one subset of ME/CFS patients, a different subset has it as an avoid). Vitamin D is a very mild avoid — but given the EBV issue above, I would ignore it and make that judgement call based on blood tests.

This also may apply to B-vitamins — none of the B vitamins are strong avoid, so a B-Complex is fine.

I have filtered the rest of the list to only the to take, coffee is sitting high in the list which appears to agree with “I dealt with the fatigue with regular consumption of coffee/tea throughout the day“. It helps in additional ways on shifting the microbiome.

GarlicTake4 gm/day423.5
HesperidinTake1.5 gm/day418.1
NACTake2400 mg/day410.1
MelatoninTake10 mg/day386.1
LuteolinTake400 mg/day385.8
Coffee or non-herbal teaTake4+ Cups/day313.4
CurcuminTake3 gm/day239.2
BaicalinTake123
GlycineTake15 gm/day119
EchinaceaTake4 gm/day109.5
Bilberry fruit extractTake40   g/day Vaccinium myrtillus powder109.5
PiperineTake109.5
Tea Tree oilTake109.5
FisetinTake20 mg/day99
PolyphenolsTake3 gm/day95.3
Raspberry fruit (black raspberry)Take50 gm/day61.5
WalnutTake75 gm/day30.5
Olive leaf extractTake700 mg/day24

Looking at the details of the Consensus Report

There are a few items not in the simplified list that are worth calling out:

Comparing Suggestions from PubMed Studies

  • Insomnia — only 3 bacteria matched
  • Sleep Apnea – only 3 bacteria matched
  • ME/CFS without IBS – 7 bacteria matched – We get good agreement with the above
From ME/CFS without IBS

Comparing Suggestions from Special Studies

As a result of this email (and several others received this week), I looked at Special Studies suggestions for some specific people. My expectation when I did special studies was that the suggestions would converge tighter — so some people that is true. For other people, like this person is it false. For more information read the blog post: Caution: Special Studies Suggestions

I noticed that most of the results had inulin, etc – which are to avoid above and appears to make the person worse.

  • Chronic Fatigue Syndrome (CFS/ME) – 52 bacteria some agreements and some disagreements
  • Unrefreshed Sleep — 62 bacteria matched
  • ME/CFS without IBS – 94 bacteria matched

I will be using this person sample to experiment with revised algorithms for Special Studies.

Probiotics

The top probiotic from KEGG data are E.Coli probiotics. Both Mutaflor and Symbioflor-2 (commercial E.Coli probiotics) are on the to take consensus list.

The next usually available item on the KEGG list is Bacillus subtilis, followed by Bacillus subtilis subsp. natto. As cited above, Natto is easily available in Japan.

Looking at Modelled Food Suggestions

Looking at the Flavonoids, we see just two things: Bananas and Barley. Rice is on the slight avoid (which may be a challenge for Japan).

We do not fair much better with Food Contents 🙁 A Guide to the Different Types of Tofu in Japanese Cuisine

This was an unexpected frustration. I wait back to the algorithm and made it less conservative. By this I mean, not eliminating items where there are contradictory results from studies. This resulted in in more suggestions, some Japan specific [there are 50 items acquired in Japan on the list]

I was going to leave the algorithm with the more relaxed condition. I then did cross-validation with the consensus and found that most of the items appearing as take using the relaxed filter were on the avoid list of the consensus. Tofu, which showed up with the strict criteria, is on the consensus to take list (as in Soy).

Why do we have any disagreements? The root problem is not sufficient studies – often with contradictory results — one may be on people with diabetes and another people with asthma. Existing conditions (and in some cases severity) can result in difference response. The microbiome is not a machine but a complex society that interacts with a lot of things

The Hail Mary Exploration

I redid the consensus and included prescription items. For many people, the pharmaceuticals are way down the to take list. Herbs and probiotic having a higher positive weight often. For this person, this was not the case. What was also unusual was none of the antibiotics that are recommended in other ME/CFS analysis (and which are used for ME/CFS – i.e. cross validation) are anywhere near the top of the list. What I found listed near the top of the pharmaceuticals were:

My immediate, due diligence, suggestion is to get testing for cholesterol, hepatitis and fungal infections. Was the “EBV/Mono-type illness” perhaps hepatitis? Two of these can result in chronic fatigue. In terms of special studies, ME/CFS (three variations) were poor matches (one was the bottom of the list). Using US National Library of Medicine studies, he is at the 29%ile.

What I find interesting is that soy is a recommendation, and we find these studies..

In terms of having the typical microbiome for someone that has a ME/CFS diagnosis — he does not match. He is also at the 0%ile for hypercholesterolemia (High Cholesterol), 8%ile for GERDs (usually common for a subset of ME/CFS).

My gut feeling is that he was not sufficiently tested before the ME/CFS label was slapped on him. His microbiome is not a match. Nothing match his symptoms to the microbiome associated conditions that I have data on.

FEEDBACK FROM READER AFTER READING

Those are very interesting points. Since my initial symptoms in Korea, I was diagnosed with Gilbert’s syndrome, an excess of Bilburin. I did get my liver checked (due to slight yellowing of the eyes) out but they don’t seem to have found anything (Over a decade ago so my memory is pretty spotty.) I think over the years in college I got MRI’s and various bloodtests with obviously no real diagnosis. Even so, my life was very active over that decade. I lived in China for a few years, frequently attended the gym, also did a fair share of partying, have always had a big appetite. Minimal impairment throughout my life overall.

Since getting sick a few years ago in Japan, I got a lot of different tests, including thyroid and diabeties. If I rifle through all the different result sheets (I have quite a few), a few things of note:

Dec. 2020 I was positive for EBVVCA-IgG which my doctor told me meant that I had had EBV in fairly recent past. No treatment was suggested.

Feb.. 2020 I had slightly elevated liver enzymes (ALT, GTP) (Not surprising given my frequent social drinking in my 20s) which persisted until April 2021 and seemed to have resolved. This was explained by lowered alcohol consumption. Never received a suggestion for follow-up or differential diagnosis.  

Persistently higher tryclycerides (I have gained some weight since my illness, matches with the atorvastatin suggestion!) and CRP indicating inflammation. Suggested to lose weight and exercise (The latter being somewhat problematic for me.) Back in my weight-lifting days, I drank lots of milk and overall had a high-fat/protein diet. Since I recently stopped drinking so much whole milk, I wonder if that will resolve it or not.

Before I moved recently I had been going to a cfs clinic which conducted sleep studies (of which I have had several over the years, indicating that I do not have sleep apnea, although that was my thought for years.) and did some other tests indicating I had high stress/inflammation. He gave me vitamins, CoQ10 (which I ordered myself) and anti-depressants for sleep. (Interesting I score high for Depression (47%) but up until the last few years I had a very active lifestyle, I don’t think depression fits my physical symptoms at all. I’ve always been very social and generally on the adventurous side. Still am, just don’t have the physical stamina I used to. I requested a prescription for Piracetam (all of the -tams were recently regulated in Japan) and he refused.

I haven’t gone back there since as I felt like the approach he had was very symptoms based and surface level. Reading your recovery stories, I pretty much ruled out getting any kind of prescription anti-biotics or being able to utilize those out here. I don’t know how the legal system works here in Japan, but my own and other anecdotal experience tells me that doctors here don’t enjoy doing things off-label, it’s an extremely by-the-book conservative approach to medicine. Fortunately, if you have a specific, known medical problem, you can get extremely professional and competent care here.

It is very interesting that I do not fit in the ME/CFS microbiome profile. An infection with Hepatitis or a fungus at some point could fit, especially given that I’ve spent time in a variety of different environments. I think I could easily get tested for Hepatitis here, it will just have to wait until next month (Currently very busy as a **** .) As far as fungus goes, usually I hear about “Candida,” any suggestions of what kind of fungus I should perhaps be looking out for would be helpful.

I will have to think about how I will go about getting tested for fungal infections here, it is somewhat difficult to explain my issues to doctors and get them to take it seriously. Definitely a good idea to also pursue a potential alternative diagnosis though, the data certainly doesn’t rule it out.

You have given me a lot to think about, thanks again for all of your consideration!

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 appears to 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.

I use modelling and various mathematical technique to estimate forecasts when there is no hard data available.

New Suggestions Page — Food Centric

I have been in dialog with a microbiome testing firm on incorporating my suggestions engine into their site. One of their requests was to provide more information on foods. Of course, if there are no studies than how can you make suggestions?

It is possible to model likely impact of foods by looking at what is in them. That information is available from:

So the process using existing pubmed studies to identify the constituents of the food that impacts certain bacteria and then aggregate these constituents to get a modelled benefit from the food.

The results are two tables (depending on which decomposition approach is used).

This is on the Changes Tab

This lists only things that are entirely one way or the other.

Appears to Cross Validate

I did some of the other suggestions methods, built a consensus report and then looked for Almonds on the same sample and found agreement. Same with Barley, Basil, and Buckwheat. Some suggestions from the second list have disagreements (not unexpected).

I would suggest that that you see how it works for your samples between these two approaches.

For your amusement, the second list is LONG (typically 800+ items) and for those that drink wine, may be amusing to scan..

Other Labs

This has been added to the define suggestions page. Both buttons open the suggestions in new windows so it is easy to switch back and forth.

If you have already uploaded a sample, a link has been added there.