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,

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.


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!


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.


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
GlycineTake15 gm/day119
EchinaceaTake4 gm/day109.5
Bilberry fruit extractTake40   g/day Vaccinium myrtillus powder109.5
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.


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.


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.

Caution: Special Studies Suggestions

Special Studies are a conceptual thought experiment. The logic is simple, identify the bacteria that are have major statistical significance from the reference. Then use these bacteria with the weight that each has being the z-score to generate suggestions.

The first reviews that I did using them had good results and agreement with my preferred trio to build consensus, namely:

This last week I have gotten several emails from people who got counter-indicated suggestions. I have verified that for their samples, it produces contrary suggestions.

Digging into the mathematics and fuzzy logic being used, I see several possible failure points that I want to slowly investigate. The top failure points are:

  • Using the z-score for the weight to give for each desired shifts. A different formula may resolve it. Two candidate formula are:
    • z-score * incidence of bacteria being seen
    • z-score * function(bacteria count) — with many possible functions
    • The z-score cut off is too low, I am using 5.0 at present, it may need to be raised to a higher value.
  • The criteria for picking a bacteria to include may not be specific enough, so a lot of bacteria that are fine are included. This can result in excessive noise in the suggestions
  • The data available for suggestions at the species levels that we are working are insufficient (and in some cases, may not exist). A lot of the species flagged are rarely seen in studies showing changes.

Bottom Line

Use the suggestions generated with great caution. If they compliment the suggestions from the three preferred consensus methods listed above — good. If they contradict, keep to the original consensus method — I have been getting consistent report that they work. The special studies suggestions are getting inconsistent results.

A special study with a z-score below 6.6 is very suspect and should be ignored.

Brain Fog – Recap and what is known

A reader contacted me over a new post on Biomesight – How to reduce brain fog. He was concerned over the content (knowing that I have often researched and posted on brain fog), so I am doing this post to provide some clarity on brain fog. (Bad pun: Remove some fog from brain fog)

What is Brain Fog?

  • The term brain fog is a vague term that has been defined in the literature as a combination of the following more accurate (and measurable by tests) conditions. A better term is executive dysfunction [2015] or Cognitive Fatigue [2014]. The literature goes back to at least 1989. I know from personal experience, I have taken them from professional psychologist, and other in the family has too.
  • Some people will perform badly on all tests, other will perform poorly on certain tests only.
Tests used to evaluate objectively brain fog, Executive Dysfunction [2015]

Related forms include

IMHO, if you do not have the majority of the above, the term may be misapplied.

For different diseases, what constitues brain fog can vary, for example:

The clinical picture typically affects visuo-spatial immediate memory (g = − 0.55, p = 0.007), reading speed (g = − 0.82, p = 0.0001) and graphics gesture (g = − 0.59, p = 0.0001). Analysis also revealed difficulties in several processes inherent in episodic verbal memory (storage, retrieval, recognition) and visual memory (recovery) and a low efficiency in attentional abilities.

Systematic review and meta-analysis of cognitive impairment in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [2022]

Common Conditions Having it

The list of conditions having issues somewhere in the executive function space is large, just a few are listed below.

Many of the above have distinct microbiome signatures and thus the hope of getting a universal microbiome signature for brain fog is an ideological belief. This appears to be confirmed in the analysis from Special Studies … Brain fog strongest z-score is just 5.2. This is lowest significance level of 26 items evaluated, the next lowest is General Fatigue. IMHO, there may be no true significance, the z-scores numbers were not adjusted for False discovery rate and incidence of reporting.

Most people will agree that there is no magic cause or microbiome signature for general fatigue — it could be an issue with iron levels, excessive lactic acid (impairment in clearing it), blood circulation issues, respiratory issues etc.

Brain fog could be described as mental fatigue and thus the same wide variety of issues can be involved. For ME/CFS, the dominant causes for brain fog, according to the literature are mentioned in some of my prior posts:

For Long COVID, we should also consider damage to the lungs impacting oxygen levels.

Concerns about Biomesight – How to reduce brain fog

My first concern is simple, the belief of there being a common microbiome pattern is very questionable. There are likely patterns, for example, a microbiome pattern that results in higher d-lactic acid production; a pattern that results in lower d-lactic acid production; a pattern that inhibits one of the many steps in the coagulation cascade; a pattern that overloads one of the many steps in the coagulation cascade; a pattern that causes vascular constriction; a pattern that cause inflammation; a pattern that inhibits the absorption of iron…and on and on. There is not a single pattern that applies to all.

My second concern is a failure to cross validate/document. D-lactic acid is well associated with brain fog in the literature, ” Dlactic acidosis is characterized by brain fogginess (BF) and elevated D-lactate“[2018], Recent research indicates that dlactic acid may inhibit the supply of energy from astrocytes to neurons involved with memory formation.  [2010]. It is not mentioned once in the post (as of this time).

When a statement like this is made “Unsurprisingly, high ethanol producers in the gut based on research findings (separate from what we are seeing from the Biomesight dataset) is associated with brain fog.” I would expect links to these research papers to be included for the reader to follow up. Ethanol is drinking alcohol, booze – which has me very curious about the links and especially if they are seen with many of the conditions cited above.

I am very curious because I use KEGG data to see if any compound production/consumption was statistically significant in Special Study: Neurocognitive: Brain Fog, and ethanol was not found to be statistically significant. Searching for ethanol on Pub Med, we find “Lactic acidosis and acute ethanol intoxication [1994]” and “SEVERE LACTIC ACIDOSIS SECONDARY TO ACUTE ALCOHOL INTOXICATION” [2021] but that was from explicit ethanol (alcohol) consumption.

This does lead me to a model for alcohol intolerance developing with ME/CFS, which I posted here [Alcohol Intolerance in ME/CFS – A Model].

How does special studies compared to Biomesight post

The table below shows no agreement between my special studies and their findings. We used different statistical process, but finding not a single agreement should be a red flag on relying on the data. While I have a smaller sample (approximately 1/3), the data processing to get the microbiome data was identical.

Special Studies
Escherichia coli (species)5.3
Lactiplantibacillus pentosus (species) 5.1
Shuttleworthia (genus) 5.1
Escherichia (genus) 4.5
Veillonella (genus) 4.4
Veillonella dispar (species) 4.4
Staphylococcus pseudolugdunensis (species) 4.2
Clostridium cellulovorans (species) 4.1
Class DeltaproteobacteriaX
Species Bacteroides uniformisX
Species Bacteroides cellulosilyticusX
Species Phascolarctobacterium faeciumX
Genus BacteroidesX
Species Anaerotruncus colihominisX
Species Faecalibacterium prausnitziiX
Genus PrevotellaX

Bottom Line

I do not believe that we can aggregate all microbiome samples reporting brain fog into a single set and find a universal pattern to address a priori. The numbers from Special Study: Neurocognitive: Brain Fog were the weakest of all special studies and, based on some other recent work in progressed, results may be adversely affected by sampling bias, sample quality, and false detection rate.

A mother with Premenstrual Dysphoric Disorder

Back Story For Mother

“Lots of high % potential health stuff. In real time, mother’s very hormone sensitive . Gets like a Premenstrual dysphoric disorder (PMDD) state , feels depressed. Struggles with anxiety and depression in general . Notice she’s been getting allergies. During the birth of 2nd child two years ago; mother had to get vancomycin because she was strep B positive. When the family get sick, the mother gets the sickest of the 4 of us unfortunately. Mother caught COVID in Sep 2022. Mother’s cycles in 2021 started to be heavy where before that never happened. As a kid, mother was on Accutane a lot. When mothers results through biomesight I also got a message that said unusually small file size or something along those lines.”

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.

Mother Overview

  • Jason Hawrelak Recommendations – 99.7%ile (better than most), High Roseburia, Blautia. The others are low

Checking on the two studies that I could find Premenstrual dysphoric disorder

If you can locate any other studies, please send to me.

Tax NameShiftPercentile
Bacteroidia (NCBI:200643 )Low4%ile
Anaerotaenia (NCBI:1843206 )Highnot reported by lab
Bifidobacterium (NCBI:1678 )High80%ile
Blautia (NCBI:572511 )High98%ile
Butyricicoccus (NCBI:580596 )Lownot reported by lab
Collinsella (NCBI:102106 )High0%ile
Extibacter (NCBI:1918452 )Lownot reported by lab
Megasphaera (NCBI:906 )Low92%ile
Parabacteroides (NCBI:375288 )Low67%ile
Bacteroidetes (NCBI:976 )Low4%ile

This suggests that we have a general match with the literature and should include in our consensus, a hand picked set of suggestions.

There is an abundance of bacteria which are there, but at low levels.

We have an impressive list of bacteria deemed unhealthy. Note that counts are often small (agreeing with the abundance of bacteria at low levels seen above).

NameRankPercentileCountCommentMore Info
Anaerotruncus colihominisspecies782380Not Healthy PredictorCitation
Bacteroides fragilisspecies745659PathogenCitation
Blautia productaspecies751440Not Healthy PredictorCitation
Collinsellagenus010High COVID RiskCitation
Doreagenus9723040Increased COVID riskCitation
Eggerthella lentaspecies993469Not Healthy PredictorCitation
Finegoldia magnaspecies91830Infectious bacteriaCitation
Granulicatella adiacensspecies8480Not Healthy PredictorCitation
Peptoniphilus hareispecies6750Infectious bacteriaCitation
Peptoniphilus lacrimalisspecies78170Infectious bacteriaCitation
Peptostreptococcus stomatisspecies88150Not Healthy PredictorCitation
Prevotella timonensisspecies951890Infectious bacteriaCitation
Ruminococcus gnavusspecies9962200Not Healthy PredictorCitation
Staphylococcus haemolyticusspecies7240PathogenCitation
Streptococcus vestibularisspecies65370Not Healthy PredictorCitation
Veillonella atypicaspecies94859Not Healthy PredictorCitation

Potential Medical Conditions Detected had at 99%ile, Schizophrenia, which suggests some overlap with PMDD.

Going Forward

I added a new choice to the site that gets canned suggestions for Bacteria Deemed Unhealthy above because of the large number of bacteria flagged in this sample.

The new option

The suggestions for this person with this new option.

33 bacteria was selected.

Building the Consensus

I am building from:

  • Hand Picked (see above focused on PMDD) (4 picked)
  • Unhealthy Suppression – just added (33 picked)
  • Outside Range from Nirvana/CosmosId (5 picked)
  • Outside Lab Range (+/- 1.96SD) (6 picked)
  • Outside Box-Plot-Whiskers (60 picked)
  • Outside Kaltoft-Moldrup (95 picked)

The top items to suggested to take are shown below (meat and B-vitamins are concentric):

The top items to suggested to avoid are shown below


We have a challenge here, take lactobacillus rhamnosus gg (probiotics) by itself is a -409, but in combination with propionibacterium freudenreichii it is 190-263. This suggests that bacteria as a supplement ( Nutricology/Securil ) or lots of real Emmental cheese (which uses it).

Similarly lactobacillus salivarius (probiotics) is a negative -275 but Lactobacillus salivarius UCC118 is a positive 285. I would avoid it, instead of playing probiotic roulette.

The next one on the list as a reasonable candidate is lactobacillus fermentum (probiotics), then mutaflor escherichia coli nissle 1917 (probiotics).

Going over to KEGG suggestions, the top choices (not in Prescript Assist which is a negative) are (in order)

Which points to microbiome labs/ megasporebiotic OR organic 3 / primal soil (see probiotic page for other choices)

My suggestion for rotation would be:

Curiosity Question from User

“for curiosity’s sake, is there any way i can find the small number of actionable bacteria affected by all these foods?”

taxonTax NameTax RankModifier that Impacts
28116Bacteroides ovatusspecies1382
29523Bacteroides sp.species1381
626931Bacteroides oleiciplenusspecies1381
357276Phocaeicola doreispecies1381
817Bacteroides fragilisspecies1381
820Bacteroides uniformisspecies1381
387090Phocaeicola coprophilusspecies1380
674529Bacteroides faecisspecies1380
1365140Bacteroides sp. J1511species1380
246791Bacteroides sp. 35BE35species1380
371599Bacteroides sp. XB12Bspecies1380
1244208Bacteroides sp. 2011_Ileo_VSA_D11species1380
151276Bacteroides coprosuisspecies1380
93975Bacteroides sp. AR29species1380
338188Bacteroides finegoldiispecies1380
One answer to the question
ModifierModifier typeBacteria Impacted
berberineHerb or Spice2101
glycyrrhizic acid (licorice)Herb or Spice2067
Human milk oligosaccharides (prebiotic, Holigos, Stachyose)Prebiotics and similar2054
triphalaHerb or Spice2008
gentamicin (antibiotic)sAntibiotics, Antivirals etc1961
lactobacillus plantarum (probiotics)Probiotics1856
azithromycin,(antibiotic)sAntibiotics, Antivirals etc1829
trimethoprim (antibiotic)sAntibiotics, Antivirals etc1810
lactobacillus reuteri (probiotics)Probiotics1795
ironVitamins, Minerals and similar1738
Slippery ElmHerb or Spice1718
neomycin (antibiotic)sAntibiotics, Antivirals etc1717
zincVitamins, Minerals and similar1686
foeniculum vulgare (Fennel)Herb or Spice1686
folic acid,(supplement Vitamin B9)Vitamins, Minerals and similar1666
amoxicillin (antibiotic)sAntibiotics, Antivirals etc1661
resistant starchPrebiotics and similar1650
N-Acetyl Cysteine (NAC),flavonoids, polyphenols etc1624
streptomycin (antibiotic)sAntibiotics, Antivirals etc1620
cinnamon (oil. spice)Herb or Spice1586
The Alternative answer

Best Talks from ISB Virtual Microbiome Series 2022

I attended this series of talks and for the readers of this blog I link to the videos in terms of my preferences below. The first ones are very technical, Day Three is much easier watching.
Unfortunately, they did not post the videos, talk by talks..

  • Dr. Katherine Amato on Day 3 (hour 3) is likely the best starting one.
  • Dr. Poyet Day 3 (hour 1) on Industrialization Microbiome
  • Dr. Iraola Day 3 (hour 0) – on the Microbiomes of South America etc
  • Day 3 hour 2 — very interesting on the impact on the microbiome of anal intercourse…. there is significant impact.

Fatigue — candidate cause: Hypoxia

This is a summary of items that may be the cause. This assumes that a lack of oxygen getting to tissue (or the brain) is the cause. Note that if the brain is tired(oxygen starved), that there may be false signals saying the body is exhausted because the brain does not have the energy to manage the body. The sources are typically from Chronic Fatigue Syndrome. Some of these may be related to the microbiome (lack of studies). It is suspected that many people are borderline (have no apparent issues) and then some event pushes them over the edge into fatigue.

This is intended as a checklist to review with your medical professional. Items should be objectively excluded by actual tests and not subjectively excluded (often a response if the professional does not know how to test). See Hypoxia[2022] and Hypoxia (medical)

Coagulation Issues

The typical scenario seems to be an inherited or acquired (epigenetic — sometimes from a virus infection) coagulation defect. Some step of the coagulation cascade gets “constipated” with the result being what is often called “sticky blood”. It only takes one step.

If the blood gets thick, it gets slow and hence less oxygen gets to the body and the brain.

Most “blood thinners” only impacts one of these steps (with heparin being the main exception). Taking excessive supplements that impacts the same step may result in long bleeding time or easy bruising.

Note: We are talking about sub-clinical (i.e. not having a stroke or blood clot) levels. The lab levels may not be abnormal, just low (or high).

Low Iron Or Impaired Heme

Hemoglobin is the iron-containing oxygen-transportmetalloprotein in the red blood cells of all vertebrates  Hemoglobin in the blood carries oxygen from the respiratory organs (lungs or gills) to the rest of the body (i.e. the tissues). There it releases the oxygen to permit aerobic respiration to provide energy to power the functions of the organism in the process called metabolism. [wikipedia]. Hemogloblin can be inhibited by some chemicals (Carbon Monoxide [2022] and the pH of the blood (Bohr effect [2021]) are the most common. pH is influenced by the microbiome.

Iron insufficiency and hypovitaminosis D in adolescents with chronic fatigue and orthostatic intolerance. Restless leg syndrome (RLS) is  negatively correlated with ferritin / iron [2012] and RLS is also co-morbid with CFS (i.e. the less iron, the more likely you will have RLS).

For example, Staphylococcus aureus is known to adversely impact iron [2022]

Malformed Red Blood Cells

Back in 1997, Dr. Les Simpson in New Zealand wrote “Myalgic Encephalomyelitis (ME): A Haemorheological Disorder Manifested as Impaired Capillary Blood Flow” observed this in CFS patients. “So it has been proposed – first at the Cambridge Symposium on ME in 1990 and in another article in 1998, that ME is a dysfunctional state resulting from reduced rates of capillary blood flow due to the presence of shape-changed, poorly-deformable red cells” [source]

It should be noted that SPECT scans show the expected effects of shape-
changed, poorly deformable red cells in reducing cerebral blood flow in
regions which by chance have smaller than usual capillaries.

TheBMJ, Chronic fatigue syndrome or myalgic encephalomyelitis [2007]

Inflammatory hypoxia

Hypoxia and inflammation are frequently co-incidental microenvironmental features of sites of concentrated physiological or pathological immune activity.

Hypoxia activates hypoxia-inducible factor, which is a major regulator of multiple aspects of immune cell function. Consequently, hypoxia plays a key role in the regulation of immunity and inflammation.

The impact of hypoxia on immunity and inflammation is site-specific and cell type-specific.

Pharmacological hydroxylase inhibition, which activates hypoxia-sensitive pathways, is profoundly protective in multiple models of inflammation.

Regulation of immunity and inflammation by hypoxia in immunological niches [2017]

Low Blood Volume

David Bell, M.D. did a study in 1995 (twenty years ago) finding about low blood volume. Cort Johnson has an 2015 update by Dr. Bell that is worth reading. “In contrast, ME patients have a volume that can be as low as 50% of normal.”

Small Heart Size

“A considerable number of CFS patients have a small heart. Small heart syndrome may contribute to the development of CFS as a constitutional factor predisposing to fatigue, and may be included in the genesis of CFS.” [2008]

” Echocardiographic examination revealed that CFS patients with “small heart” had an actually small LV chamber and poor cardiac performance. Cardiac functional changes evaluated by repeated examinations appeared to be directly associated with the severity of their symptoms. Small heart syndrome with impaired cardiac function may contribute to the development of CFS through low cardiac output as a constitutional factor.” [2009]

Enzymes and thus Microbiome

“We’ve discovered that the muscles regulate oxygen consumption in a very precise way using the oxygen-sensitive enzyme FIH,”

How muscles regulate their oxygen consumption [2018]

” cytochrome P450 (CYP), monoamine oxygenase (MAO), and cyclooxygenase (COX). CYP enzymes are central players.. are important for therapeutic intervention and treatment of neurological and inflammatory diseases”

Analysis of activity and inhibition of oxygen-dependent enzymes by optical respirometry on the LightCycler system [2010]

Obstructive Sleep Apnea

Note that blood platelets activation is part of the coagulation cascade above.

Snoring, collapse of upper airways and intermittent hypoxia are main causes of smoldering systemic inflammation in patients suffering from obstructive sleep apnea. The systematic inflammation is considered one of the key mechanisms leading to significant cardiovascular complications. Blood platelets, formerly not even recognized as cells, are currently gaining attention as crucial players in the immune continuum. Platelet surface is endowed with receptors characteristic for cells classically belonging to the immune system, which enables them to recognize pathogens, immune complexes, and interact in a homo- and heterotypic aggregates.

Obstructive Sleep Apnea: From Intermittent Hypoxia to Cardiovascular Complications via Blood Platelets [2018]