Special Study: Neurocognitive: Brain Fog

This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links.

This is now available on the Special Studies

Study Populations:

SymptomReferenceStudy
Neurocognitive:Brain Fog1020127
  • Bacteria Detected with z-score > 2.6: found 97 items, highest value was 5.3
  • Enzymes Detected with z-score > 2.6: found 309 items, highest value was 5.6
  • Compound Detected with z-score > 2.6: found 571 items, highest value was 5.8

Interesting Significant Bacteria

The top item happens to have probiotics that are known to take up residency – Symbioflor-2 and Mutaflor. All of these top items are too low levels

BacteriaReference MeanStudyZ-Score
Escherichia coli (species)7431685.3
Lactiplantibacillus pentosus (species)123255.1
Shuttleworthia (genus)288955.1
Escherichia (genus)590315004.5
Veillonella (genus)407225224.4
Veillonella dispar (species)8531274.4
Staphylococcus pseudolugdunensis (species)46204.2
Clostridium cellulovorans (species)40184.1

Interesting Enzymes

NADH is available as a supplement. It is reported to improve ME/CFS

EnzymeReference MeanStudy
Mean
Z-Score
3-phenylpropanoate,NADH:oxygen oxidoreductase (2,3-hydroxylating) (1.14.12.19)6111325.6
3-(cis-5,6-dihydroxycyclohexa-1,3-dien-1-yl)propanoate:NAD+ oxidoreductase (1.3.1.87)5981315.6
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)15144435.2
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)14674185.2
[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase (2.8.1.11)542126625.1
ATP:D-tagatose 6-phosphotransferase (2.7.1.101)4221115

Interesting Compounds

All of the top compounds had lower levels

NamesZ-Score
2-Phospho-4-(cytidine 5′-diphospho)-2-C-methyl-D-erythritol (C11436)5.8
O-Acetyl-L-homoserine (C01077)5.4
Adenosine-GDP-cobinamide (C06510)5.4
6-Deoxy-L-galactose (C01019)5.2
[Enzyme]-cysteine (C15811)5.2
Adenosyl cobyrinate a,c diamide (C06506)5.1
Xanthosine 5′-phosphate (C00655)5.1
dTDP-glucose (C00842)5.1

Bottom Line

The z-scores for bacteria are lower than Long COVID which reflect the diffusion of bacteria over time. Trying to tackle at the compound or enzyme levels becomes excessively complex. Working at the bacteria level appears viable, but do not expect as many bacteria matches to appear.

Proforma Suggestions

A new specialized selection of suggestions based on statistical significance

Going to [Changing Microbiome] page you will see a new box appearing. It may or may not contains links to suggestions. It is scoped to BiomeSight interpretation of microbiome data. If you have Ombre/Thryve samples, do not despair, you can move your raw data to BiomeSight and send it to Microbiome Prescription. It is simple and fast as shown in this video đź“ąVideo on Transferring Data from Ombre/Thryve to Biomrsight and then to Microbiome Prescription.

Actually, if you have done any of those listed below — you can follow the same process

Choices from BiomeSight.com
The counts are the number of matches to the sample currently selected.

What will appear in this list?

First, why Biomesight? — the reason is very simple, there are more samples (20% more at present and increasing then Ombre despite being in business for much less time). The bigger the sample size, the easier it is to find significant shifts.

The criteria is that there must be strong statistical significance for a good number of bacteria. My current threshold is: z-scores must all be 2.6 or higher, that is p <0.01 or 99% confidence. At least 50 bacteria needs to be identified as significant. I will be going thru the symptom list from most frequency reported to less frequently reported. Make sure that you annotate your samples with your symptoms.

NOTE: The numbers below reflect the statistics when various posts were done. The numbers are recomputed at least bi-weekly.

StudySizeBacteria
Z-Score
Enzyme
Z-Score
Compound
Z-score
Long COVID15710.6-12-22.7
General ME/CFS1596.64.53.1
ME/CFS with IBS528.46.3n/a
Tinnitus (ringing in ear)736.37.1n/a
Histamine or Mast Cell Issues568.56.1n/a
Neurocognitive: Brain Fog1275.35.65.8
Neurocognitive: Can only focus on one thing at a time795.86.7n/a
Neurocognitive: Difficulty paying attention for along period of time755.25.0n/a
Neurocognitive: Problems remembering things696.35.9n/a
Difficulty finding the right word677.05.5n/a
Post-Exertional Malaise (PEM)626.27.0n/a
Bloating985.45.4n/a
Constipation839.95.2n/a
Unrefreshing Sleep1075.55.2n/a
General: Fatigue1305.25.73.9
Worsening of Symptoms with Stress.926.95.1n/a
Irritable Bowel Syndrome556.76.1n/a
Poor Gut Motility558.86.4n/a
Autism678.27.6n/a
Easily Irritated539.95.9n/a
Anxiety/Tension596.48.4n/a
Allergic Rhinitis (Hay Fever)428.66.8n/a
Hypersensitivity to Noise566.98.1n/a
Intolerance of Extremes of Heat and Cold548.86.7n/a
Cold Extremities7812.65.3n/a
Small intestinal bacterial overgrowth (SIBO)356.57.9n/a
Depression537.88.3n/a
Allergies And Food Sensitivity739.96.8n/a
Alcohol intolerance + Medication sensitivities598.67.9n/a
The bigger the z-score (positive or negative), the more significant
  • I should point out that these bacteria may not be the cause, rather they may be ‘the canaries in the coal mine’ of the microbiome. These studies’ methodology determines association and not causality.

An additional criteria is that they need to be clear abnormalities with the KEGG Enzymes estimate.

Enzyme (KEGG Identifier)Reference MeanLong COVID MeanZ-Score
S-adenosyl-L-methionine:16S rRNA (guanine1516-N2)-methyltransferase (2.1.1.242)17373103707.1
ATP phosphohydrolase (ABC-type, teichoic-acid-exporting) (7.5.2.4)1229172506.3
(S,S)-butane-2,3-diol:NAD+ oxidoreductase (1.1.1.76)966655256.3
(S)-acetoin:NAD+ oxidoreductase (1.1.1.304)966655256.3
UDP-N-acetyl-alpha-D-glucosamine:beta-D-mannosyl-glycoprotein 4-beta-N-acetyl-D-glucosaminyltransferase (configuration-inverting) (2.4.1.144)8372406
acetyl-CoA:propanoate CoA-transferase (2.8.3.1)977255696
Example for the enzyme shifts

I have done two with acceptable results and have made them available. More will be added over time (each one takes a fair amount of time).

US National Library of Medicine Studies are difficult to use

I have their results available and on the site, including as bacteria filters. The problem is that all of those results are very sensitive to the lab being used and the software processing the results. See The taxonomy nightmare before Christmas… for background. In the absence of better information, they are the best we have — until now. With these suggestions, the lab and the software being used are the same and also the one that your results are done by.

Background

Interesting Observation

For both of the above, lower levels of a large number of bacteria was the common pattern. These bacteria are not present in all samples, and most of the studies seen on the US National Library of Medicine look only at bacteria found in all samples. That approach will exclude the bacteria that we find are significant.

You may find dozens (in this case 6 dozens!) of bacteria selected

A second item to be aware of is that often those PubMed studies may consist of just 50 people (control and patients). In our analysis, we have 1200+ people with often more then 120 people with a specific condition. Statistically, we are more likely to detect more associations than those studies. It’s a number’s game.

I am still tuning the suggestions engine, so expect reordering of suggestions occasionally. The suggestions pass the reasonableness test.

Quick Cross Validation

I ran the suggestions only for prescription drugs for ME/CFS and the top four suggestions are listed below. Three of the top four are used by ME/CFS physicians such as Dr. Cecile Jadin [Src], Philippe Bottero [src], G. L. Nicolson, M. Y. Nasralla, A. R. Franco, K. De Meirleir, N. L. Nicolson, R. Ngwenya & J. Haier [Src]. These physicians all report various degree of success.

  • azithromycin,(antibiotic)s
  • atorvastatin (prescription)
  • minocycline (antibiotic)s
  • doxycycline (antibiotic)s

Atorvastatin is an oddity with no studies for its use with ME/CFS. On the flip side, generic statins were high on the avoid list. It would be nice if someone did a clinical trail for this explicit type of statin.

Comparing 4 ME/CFS Samples with New Tool

A reader pinged me about new results so I thought it would be good to look at his series of 4 samples from Ombre/Thryve to help people interpret their own results. I am using the tool described in Comparing Samples – Update.

  • As you can see, the bacteria count do bounce around, with the change from the last sample being a definite improvement
  • There is a ongoing shift towards overproduction of Enzymes, but this does not cascade into increased compound (Produced – Consumed)
  • Several of the External Criteria measures showed improvement (2 less) and less showed more (1 more)

The reader has prior reviews:

Measure6/15/20225/16/20223/15/202211/21/2021
Lab Read Quality4.84.83.64.2
Bacteria Reported By Lab515669593473
Bacteria Over 99%ile0101
Bacteria Over 95%ile422219
Bacteria Over 90%ile22404821
Bacteria Under 10%ile431122387
Bacteria Under 5%ile1860546
Bacteria Under 1%ile0902
Lab: Thryve NULL
Rarely Seen 1%32090
Rarely Seen 5%1167389
Pathogens37423833
Outside Range from JasonH7799
Outside Range from Medivere17172020
Outside Range from Metagenomics8877
Outside Range from MyBioma881010
Outside Range from Nirvana/CosmosId23232222
Outside Range from XenoGene881010
Outside Lab Range (+/- 1.96SD)2762
Outside Box-Plot-Whiskers42717225
Outside Kaltoft-Moldrup11314814391
Condition Est. Over 99%ile0000
Condition Est. Over 95%ile0000
Condition Est. Over 90%ile0010
Enzymes Over 99%ile9148535
Enzymes Over 95%ile599305182147
Enzymes Over 90%ile719629438458
Enzymes Under 10%ile707138169
Enzymes Under 5%ile1928478
Enzymes Under 1%ile2000
Compounds Over 99%ile69314319
Compounds Over 95%ile18627719089
Compounds Over 90%ile303435220118
Compounds Under 10%ile321528333133
Compounds Under 5%ile195378310100
Compounds Under 1%ile011826742

Bottom Line

The microbiome is a dynamic system and as shown in the image below, it is not a simple straight path. There is no single measure that indicate the current status of the gut, rather a variety of measures.

The latest sample showed (compare to prior):

  • Drop in compound extremes
  • Increase in high Enzyme production — this may hint at the body stocking up on supplies for an attack of troublesome bacteria
  • A drop of bacteria out of range by both external criteria and Microbiome Prescription Criteria.

Reader’s Comments

This round I restarted the b.lactis by custom probiotics. I did it last test and took a month break and it came up again. 1st round doing it , the herx was kicking my butt and I lasted 10 days. This time around , only did 1 scoop at night and I was still herxing and sleeping 8 hours hard. After day 10 I did half dose mornings and half at mid day or night. Much better tolerance and body seems to respond well. Calmer, better sleep, allergies seem better. 

Now also taking rice bran, blue berries, Lactoferrin for iron, and a lot of the other high priority items. I try playing basketball 1 time a week to check my progress. I have plenty of energy to play, but if I play too hard I crash still exactly 5 hours later (impaired sleep, brain fog, fatigue , headache, inflamed stomach lasting exactly 24 hours) . Then back to normal the same day. Tried the symptom /handpick bacteria tool and focused on picking PEM/brain fog/sleep with associations.  The top modifier for that was glycemic (licorice root tincture). Added that to the mix this week. Still crash, but notice some weight loss and less belly inflammation after I play. Overall improvement in sleep and anxiety. I am still a work in progress and could be better, but seeing improvement. My post exertion crashes are the thorn in my side I haven’t been able to dent much, no clue why I crash exactly 5 hours after every time but can play and feel find right after. Couple more days of b lactis and I switch to my next probiotic L.gasseri. Then will test again in about 2 weeks!

Mystery of Crash after 5 hours lasting exactly 24 hours

I have a few suggestions to try — looking at possible mechanisms..

The goal is to see if any alters the onset at 5 hrs, thus a “tell” for possible causality.

Comparing Samples – Update

A reader asked me to compared her latest sample to her prior samples. Comparing samples can be time consuming and complex, so I revisited my past comparisons posts and created a table that saves time and add clarity.

Location of the comparison table

Bacteria Report

  • Lab Read Quality indicates the numbers of bacteria that the lab obtained. In this case, the quality of the samples were similar
    • This impacts Bacteria Reported. In this case 1/14 less, and the bacteria count is about 1/14 less. If there was a severe change, then we wish to understand why
  • Bacteria Over/Under: Between samples we would like them to be reduced (less extremes). If lab quality goes down or up a lot, then the numbers may need to be adjusted for comparison.
    • We see more than a 1/14 drop, which indicates a better microbiome.

Lab Relatives

If both labs were done with the same provider, then this section will appear. In this case we see that rarely seen bacteria goes down – a good sign.

Foreign Criteria

This applies various foreign criteria to the samples. The increase of pathogen is a potential concern. I tend not to focus on pathogens because the source data usually report “higher” or “lower” only.

Microbiome Prescription Criteria

This reports on the main approaches used for generating consensus suggestions. All of them indicate little change except KM which suggests improvement.

PubMed Conditions

This uses the literature from the US National Library of Medicine to estimate likelihood of having various conditions. It is a fuzzy estimate due to the what the studies report. In this case we see good improvement across the board.

KEGG Criteria

As above, we want to reduce extreme values (represented by high and low percentiles). What we see below is very significant improvement across the board.

Bottom Line

The above are the list of my first go-to items comparing samples. If someone has followed the suggestions from Dr.A.I. between samples (or done other things), it give a quantification of the changes that occur across multiple dimensions.

In this case, we see significant improvement over a few months! It should be noted that the various external criteria show no apparent changes, the deeper dive that Microbiome Prescription does show significant positive changes.

A Complex Microbiome Situation

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 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.

Dr. A.I. is not a person ,it stands for Artificial Intelligence – a compute program that takes facts (in this case, well over 10 millions) and use logic to come up with suggestions based on probability.

Back Story

I’ve had severe gastric symptoms for about 15 years (unstoppable daily acid reflux, severe bloating and food sensitivities/very reduced diet, upper digestive pain, chronic UTI, chronic tender lymph nodes), and milder related symptoms my whole life (recurrent sore throat, allergies, eczema, psoriasis, vitiligo, depression, anxiety, fatigue ). Since I haven’t been able to fully resolve them, I’ve also developed comorbidities (Hashimoto’s, thyroid microtumor). I’ve found your website and have gotten a bit better and have hope to keep improving. I’m trying to understand your videos and instructions on how to use your AI the best I can.

I did a number of Ubiome tests in its day, unfortunately I only downloaded the raw data for two of them, which I uploaded to your website. I am attaching other gastro tests that I believe I cannot upload since there’s no raw data, they may be useless. I also have uploaded my recent  thryve test, and I plan on having more tests done to monitor progress. I have been going back and forth with microbiome labs to try to get the raw data, we’ll see. I’m “hooked” to herbals, taking bidens for UTI for years, and tied to foods like cabbage and meat, and my microbiome shows signs that it needs a wider variety of foods as well as a rotation of probiotics, herbal antibiotics, and foods. I react very strongly to prebiotics. I can eat cruciferous veggies, meats, fish, low-carb, low oxalate NO: starches, grains, cereals, fruits, sugars, eggs, milk, legumes. Neem helped a bit with oxalate sensitivities. A few probiotics helped with mood. Then I get stuck in needing these things, the flora develops resistance.

My husband and I are both following your sites. Thank you again for all you do.

Addendum

Sending the first draft results in the following information, see Addendum Discussion at the bottom.

I am thankful you have taken my sample to analyze. This is an incredible amount of work and very illuminating on how you approach the tools on your website. I agree, my situation seems to be a bit contradictory and difficult to approach. Here are some comments and reactions to your ideas—I am not suggesting these should be included or modify your post, that is up to you…

Firstly, I would like to say, that I have already been implementing a few of the top probiotic and flavonoid suggestions for a couple of weeks and I do feel that many of my symptoms have either improved some or changed and are changing, which, for at least a decade seemed unmovable. Other are unchanged. I do not think I mentioned this before, but in general I have less hepatic region/upper digestive discomfort and when I do have some, it’s less aggressive and I recover faster. I have related this symptom in the past to oxalate intolerance. My UTI feels much better, though it is not fully gone and my reflux has more frequently better days, though these come and go. My mood has improved and I tend to be more hopeful. I’m a bit less fatigued.

The things I have so far implemented are:

  • Before I implemented any of your website suggestions, I used bidens and neem which helped a lot.
  • When I took the Ombre sample I had been doing high doses of reuteri, plantarum, longum, casei for a couple of weeks… I wonder if these have anything to do with the high Kegg.
  • I have been taking P. acidilactici as a base…
  • I did 2 courses of Symbioflor 2 (2 bottles) and Enterogermina, which I think helped. I think some results suggest I may be low in good strep too.
  • I am now on a run of B. coagulans and Equilibrium (this last one because I test low in alpha diversity)
  • I am planning a run of L. sakei and Enterogermina again next…  The prescript assist folks refuse to share an updated CoA with me.
  • I am taking artemisia, planning to alternate with neem, bidens, cryptolepis/sida

Regarding dietary recommendations, these are mostly non-negotiable at this point due to intolerances and allergies. One single pistachio a week ago gave me more bloating and worse symptoms for a couple days, so it is unlikely that nuts will be part of the solution initially. Rice bran is a big question, I have been searching for a brand that has low heavy metal analysis, but generally, I do not tolerate prebiotic fibers well at all. This is subject to change, for instance neem did help minimize a bit oxalate intolerance.

I have been using quercetin and I am waiting for a full-spectrum cannabinoid extract to arrive to try. I have had a complicated relationship with licorice in the past, but I am willing to try again. 

I do not think I can do oats yet, starches and cereals are too challenging.

The foods I eat that contain choline are salmon (once a week), beef daily and cruciferous vegetables which are the bulk of the veggies I eat because I tolerate them well, probably because of low oxalate content.

I think some killing is necessary along with the rest. The Mircobiome FX people recommended their B. subilis strain for this purpose (in their test C. difficile and B. fragilis were high) but it’s not recommended by the AI.

I will follow up with another Ombre test soon.

Analysis

Comparing results from different labs has risks. In this case, I thought it may be worth it. (I was debating about purging ubiome data since the data is stale and they consume a lot of space — I will keep them available).

I should note that I recently revised the code to use lab specific percentiles for ubiome, ombre and biomesight. This means that the numbers are more accurate despite the oddities of different labs.

05-08 Ubiome
06-29 Ubiome
2022 Thryve/Ombre

The ubiome samples had a over representation of bacteria that had extreme values (at 90% or higher). The Ombre sample had a better balance, but still with some overrepresentation of bacteria with extreme value.

Dr. Jason Hawrelak

Jason’s criteria was developed using uBiome data. And all of the samples are good. There were no significant potential medical condition on any samples. The same number of bacteria deemed unhealthy were seen on each report.

  • 05-08 – 98.8%ile
  • 06-29 – 95.6%ile
  • 2022 – 95.6%ile

The new Over and Under Population Experimental Feature

With this feature, we see much more difference between samples. The latest sample suggests that the issue may be related to too much being produced.

05-08 ubiome
06-29 Ubiome
2022

The Road Forward

There are a lot of health issues. The site supports targeting of specific issues (because that is how some people wish to proceed). In general, I have been finding the consensus with perhaps 1 or 2 specialized set of suggestions appearing to give good results. We are dealing with fuzzy data everywhere and should resist temptations to over engineer suggestions.

I looked at the Taxon Hierarchy and selected items in Ombre. There was something odd with the data as shown below.

 Bacteroidetes is part of Bacteroidetes/Chlorobi group – so the parent should be the same or more than the children, not less.

The work around is to keep choices to the family, genus and species level. Picking items with a count of 2000 or more only. The selection is shown below

The result of the hand picked is shown below, I usually truncate the list to 0.4 and higher. Both lists are relatively small!

I usually stop at 0.4 or .5

Doing the pro forma consensus building next

The consensus Report download is below.

The top items on the consensus report are similar to the hand picked results (in decreasing priority)

The avoid list:

Looking at Grains

  • Take: Oats (porridge each morning?)
  • Avoid: Barley, Rye, Wheat (a bit fuzzy, different types are on either side)

Probiotics

The top ones selected using KEGG may be hard to find in many places: enterogermina, Sun Wave Pharma / Spor Sun. The weight give them is light, so likely not much impact would be expected.

The top ones appears to be:

Again, they appear to be light in potential impact. With too high production of many things found above, probiotics may be adding wood to the fire.

Vitamins

Vitamin b7 biotin (supplement) and Vitamin C (ascorbic acid). A B-Complex has both good and bad items, so be specific to B7.

Bottom Line

This is a sample which I term “on the border of what we have knowledge about”. We can see the issues, but lack studies that we can use to correct the issues. I have encountered one like this before and after doing the first set of suggestions, the microbiome moved into a state where we are able to get a normal number of significant suggestions from. I hope this is the case here. Samples like this are a bit frustrating to me..

  • I would suggest stocking up on Spezzatina (perhaps even do what we did, buy a whole kilogram (2.2 lbs) of Amarelli Spezzatina [note: no sugar at all!]) and using them through out the day.
  • We had the space and purchased our own infrared sauna a few years ago (on sale at Costco). If you follow that path, remember lots of water and slowly work up duration. For water in the sauna, we use Gerolsteiner Natural Mineral Water (available from Trader Joe’s) because of it’s high mineral content.
  • Reduce the foods high in choline in your diet (see the list here)
  • Keep nuts (Costco/Trader Joe’s?) handy for snacks. Remember peanuts are NOT nuts.

Addendum Discussion

First, and most important: items are suggestions only. People should do only what works for them. Each item increases the odds of a positive shift a little, key word is a little. Occasionally, I will get emails from people who experienced awesome changes from a single item (Neem and Tulsi are often cited). If something is not mentioned and it helps — keep doing it!.

  • a complicated relationship with licorice in the past” In follow up email, the cause appeared to be licorice oil being used. For licorice, I strongly favor the Italian Spezzatina. This person had no problem with the Spanish equivalent… when there is an item with a suggestion, before discarding entirely, consider the following:
    • If in an oil, you may be reacting to the carrier and not the substance. On occasion, it can be preservatives in it. For example Mountain herbs is 35-45% alcohol
    • The dosage may be too high to start, I always advocate starting low and slowly increasing
    • For capsules, read Study: Herbal Supplements Full Of Contaminants, Substitutes, And Fillers [2013]
      • We rarely buy prepared capsules, instead we buy organic bulk and make our own capsules. It is both cheaper, organic sourced (very few supplement bottles cite organic) and less likely (but not impossible) to have the issues cited above.

Concerning salmon, etc. Remember everything is odds. Nothing is guaranteed. You want to shift your odds where practical.

One item that may be worth trying is Akkermansia Probiotic (link with 30% discount). Both my wife and I have, and are, using it — it has definitely made changes (I had almost the same amount that he has – 52%ile, and there was a change). The link is for by subscription — of course, once you get your first bottle, you can just suspend the subscription.

What probiotics to take/not take with a probiotic?

A reader asked this question about Lactobacillus Salivarius (NCBI 1624). I am doing it for this single strain — for a mixture, just do each one and consolidate the results.

FIRST, login to access more information. Most of the information below do not require a login.

SECOND, look up the species

From https://microbiomeprescription.com/Library/Lookup?name=Lactobacillus+sa%25&top=200

THIRD, click on that link above, this will show what helps or hurts this probiotic. Click on [Probiotics] for a start — you want to make sure that other probiotics you are taking support it. Note that I have gone thru a few retail mixtures and the probiotics fight each other! Buyer beware of mixtures! In this case we have 26 listed. 24 are friendly and 2 are hostile (bacillus laterosporus (probiotic), bifidobacterium bifidum (probiotics)

https://microbiomeprescription.com/library/details?taxon=1624

FOURTH, There is one more source of information, by looking at the associations in microbiome report. On the same page above click the red interactions button.

On the https://microbiomeprescription.com/library/details?taxon=1624 page

This will show a page of bacteria that are associated positively or negatively with this bacteria (i.e. probiotic). You will need to type in the family names:

These have a positive impact (i.e. IMPACT is > 0)
Other lactobacillus are friendly

Looking for enterococcus, pediococcus and E.Coli — we find nothing, looking at clostridium butyricum (probiotics), we do not find it, but it’s siblings appear to have a positive impact.

FIFTH, check prebiotics (they are often bunddled in probiotics) — 18 are friendly and two are hostile

SIXTH Check Herbs and Spices, the results here may impact the rotation of herb and spices. You want to take friendly when you are doing the probiotics. Although they will likely not take up residency, the chemicals that they produce while in transit are good… you do not want to reduce the production of those chemicals.

Bottom Line

Doing your homework will get much better results than just tossing them in your mouth with something that will inhibit it!

Long COVID: microbiome scents – we smell a skunk!

This is using data from the study being done with BiomeSight. We will only use their samples. After the first review, a z-score of 6.4 or higher (or a lots of items) was set as a cutoff point. The following ignore False Detection Rate.

  • Conclusion: the ENZYME production of the microbiome is by far the strongest indicator.
  • The reference set consists of 1037 heterogenous samples (i.e. no Long COVID, but a variety of medical conditions) and 154 samples with Long COVID

Taxon Patterns

Care needs to be taken with these numbers because the frequency of reporting on a bacteria is a factor that impacts the z-score. The data for this table is available at Citizen Science site and independent analysis is strongly recommended. This table is a simplified view of very complex data.

tax_nametax_rankNo Symptom MeanSymptom MeanZ-ScoreChange
Terrabacteria groupclade71504052088510.473%
Firmicutesphylum6524525028309.077%
Tenericutesphylum25626362-7.9248%
Eubacterialesorder6098884824687.979%
Mollicutesclass25626362-7.9248%
Clostridiaclass6137434877197.879%
Emticicia oligotrophicaspecies7692553-6.8332%
Faecalibacterium prausnitziispecies100292142415-6.7142%

End Product Patterns

End products only had a single item above our 6.3 z-score threshold with a very small shift.

EndProductNo Symptom MeanSymptom MeanNo Symptom StdDevChange
H2132913076.698%

KEGG Enzyme Patterns

This is where we see a massive number of patterns(182!!) with very high z-scores (i.e. 6.4 or higher). This hints that the bacteria associated with these enzymes may be a good target to modify.

EnzymeNameNo Symptom MeanSymptom MeanNo Symptom StdDevChange
dihydrourocanate:acceptor oxidoreductase58562147222-18.2251%
(S)-3-hydroxy-3-methylglutaryl-CoA acetoacetate-lyase (acetyl-CoA-forming)55210142006-18257%
(1->4)-alpha-D-galacturonan reducing-end-disaccharide-lyase54601139740-17.7256%
acetyl-CoA:kanamycin-B N6′-acetyltransferase55382140425-17.7254%
acetyl-CoA:2-deoxystreptamine-antibiotic N3-acetyltransferase56590141511-17.6250%
poly(deoxyribonucleotide)-3′-hydroxyl:5′-phospho-poly(deoxyribonucleotide) ligase (ATP or NAD+)55562141080-17.6254%
D-serine ammonia-lyase (pyruvate-forming)55931140065-17.6250%
poly(deoxyribonucleotide)-3′-hydroxyl:5′-phospho-poly(deoxyribonucleotide) ligase (ATP, ADP or GTP)55562141080-17.6254%
alpha-maltose-6′-phosphate 6-phosphoglucohydrolase57944142024-17.5245%
ATP phosphohydrolase (ABC-type, iron(III) enterobactin-importing)57953141331-17.4244%
protein-Npi-phospho-L-histidine:D-mannose Npi-phosphotransferase66964152717-17.4228%
ATP phosphohydrolase (ABC-type, Fe3+-transporting)68676154113-17.4224%
D-psicose 3-epimerase70754155871-17.2220%
D-tagatose 3-epimerase70754155871-17.2220%
2′-(5-triphosphoribosyl)-3′-dephospho-CoA:apo-[citrate (pro-3S)-lyase] 2′-(5-phosphoribosyl)-3′-dephospho-CoA-transferase77143161549-17.1209%
ATP:3′-dephospho-CoA 5-triphospho-alpha-D-ribosyltransferase78363162298-17207%
2,4,6/3,5-pentahydroxycyclohexanone 2-isomerase75196158863-16.9211%
ATP:[protein]-L-tyrosine O-phosphotransferase (non-specific)60964143510-16.9235%
acetyl-CoA:citrate CoA-transferase79352162680-16.7205%
L-aspartate:tRNAAsx ligase (AMP-forming)63596144560-16.7227%
poly(deoxyribonucleotide)-3′-hydroxyl:5′-phospho-poly(deoxyribonucleotide) ligase (ATP)69642156282-16.7224%
penicillin amidohydrolase69734151011-16.6217%
protein-Npi-phospho-L-histidine:D-mannitol Npi-phosphotransferase57950140690-16.5243%
ATP:D-erythronate 4-phosphotransferase65433145262-16.4222%
acetate:holo-[citrate-(pro-3S)-lyase] ligase (AMP-forming)90668176404-16.4195%
ATP:D-threonate 4-phosphotransferase65433145262-16.4222%
D-aspartate:[beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n ligase (ADP-forming)73487157884-16.4215%
4-phospho-D-erythronate:NAD+ 3-oxidoreductase65773145502-16.3221%
4-phospho-D-threonate:NAD+ 3-oxidoreductase65773145502-16.3221%
nucleoside-triphosphate diphosphohydrolase69217153915-16.2222%
4-amino-5-aminomethyl-2-methylpyrimidine aminohydrolase75806165018-15.7218%
ATP:D-glycero-alpha-D-manno-heptose 7-phosphate 1-phosphotransferase81281169414-15.7208%
aryl-ester hydrolase77314159122-15.6206%
palmitoyl-CoA hydrolase76772157265-15.4205%
UDP-alpha-D-glucose:1,2-diacyl-sn-glycerol 3-alpha-D-glucosyltransferase91112172382-15.4189%
D-tagatose 1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase (glycerone-phosphate-forming)75959152459-15.2201%
ADP-alpha-D-glucose:alpha-D-glucose-1-phosphate 4-alpha-D-glucosyltransferase (configuration-retaining)63077146386-15.1232%
L-glutamate:tRNAGlx ligase (AMP-forming)97313177576-14.5182%
oligosaccharide 6-alpha-glucohydrolase96720174292-14.3180%
S-adenosyl-L-methionine:tRNA (adenine22-N1)-methyltransferase96117168859-13.9176%
alkylated-DNA glycohydrolase (releasing methyladenine and methylguanine)93342182716-13.7196%
sn-glycerol 3-phosphate:quinone oxidoreductase113940189562-13.6166%
L-iditol:NAD+ 2-oxidoreductase113731190510-13.4168%
(3S)-citryl-CoA oxaloacetate-lyase (acetyl-CoA-forming)108775197009-13.3181%
N-succinyl-LL-2,6-diaminoheptanedioate amidohydrolase88237163157-13185%

KEGG Product

Products are the output of enzymes. Various enzymes may produce the same product. Our starting assumption was that products would have stronger association than enzymes. That was not shown in the data.

CompoundNameNo Symptom MeanSymptom MeanNo Symptom StdDevChange
Acetoacetate3787855442-8.1146%
Reduced electron-transferring flavoprotein106971149551-6.9140%
Dialkyl phosphate7732553-6.8330%
Indole-3-acetate7732553-6.8330%
Pseudouridine 5′-phosphate109418150579-6.7138%
3-Hydroxy-3-(methylthio)propanoyl-CoA7582494-6.7329%
3-Oxopropionyl-CoA7582494-6.7329%
N-Acetyl-beta-D-glucosaminylamine7602473-6.7325%
(2E,4Z)-2,4-Dienoyl-CoA6880995899-6.6139%
Short-chain trans-2,3-dehydroacyl-CoA103627144711-6.6140%
(2E,4E)-2,4-Dienoyl-CoA6880995899-6.6139%
4-(4-Deoxy-alpha-D-gluc-4-enuronosyl)-D-galacturonate3396147705-6.6140%
4-Hydroxyphenylglyoxylate113250152269-6.5134%
Oleoyl-[acyl-carrier protein]7352376-6.5323%
(4Z)-Hexadec-4-enoyl-[acyl-carrier protein]7352376-6.5323%
N6′-Acetylkanamycin-B3476248298-6.5139%
(6Z)-Hexadec-6-enoyl-[acyl-carrier protein]7352376-6.5323%
Pyocyanine7512381-6.5317%
(1E,3E)-4-Hydroxybuta-1,3-diene-1,2,4-tricarboxylate14304549-6.5318%
Aldose7642429-6.4318%
Molybdoenzyme molybdenum cofactor119172159672-6.4134%
N3-Acetyl-2-deoxystreptamine antibiotic3593949415-6.4137%

KEGG Substrate

Subtrate are the fuel for enzymes reaction. Various enzymes may consume the same compound. Our starting assumption was that substrate would have stronger association than enzymes. That was not shown in the data.

CompoundNameNo Symptom MeanSymptom MeanNo Symptom StdDevChange
Dihydrourocanate3802655395-7.8146%
(S)-3-Hydroxy-3-methylglutaryl-CoA3482050269-7.4144%
Electron-transferring flavoprotein106880149551-6.9140%
threo-3-Hydroxy-D-aspartate7602532-6.9333%
3-(Methylthio)acryloyl-CoA7572494-6.8329%
3-Hydroxy-3-(methylthio)propanoyl-CoA7572494-6.8329%
3-Oxopropionyl-CoA7572494-6.8329%
ADP-sugar7722553-6.8331%
Aryl dialkyl phosphate7722553-6.8331%
beta-D-Mannose7722553-6.8331%
D-erythro-3-Hydroxyaspartate7612532-6.8333%
Pseudouridine105195147050-6.8140%
N4-(Acetyl-beta-D-glucosaminyl)asparagine7592473-6.7326%
Short-chain acyl-CoA103536144711-6.7140%
(2-Amino-1-hydroxyethyl)phosphonate7522431-6.6323%
trans-2,3-Dehydroacyl-CoA6874595899-6.6140%
(S)-4-Hydroxymandelate113176152269-6.5135%
5-Methylphenazine-1-carboxylate7502381-6.5317%
Hexadecanoyl-[acp]14684753-6.5324%
Kanamycin B3472948298-6.5139%
Octadecanoyl-[acyl-carrier protein]7342376-6.5324%
(1E)-4-Oxobut-1-ene-1,2,4-tricarboxylate7392338-6.4316%
2-Deoxystreptamine antibiotic3591649415-6.4138%
Adenylated molybdopterin119083159672-6.4134%
Alditol7632429-6.4318%
beta-Carotene7202314-6.4321%
Molybdate119083159672-6.4134%

Bottom Line

Several years ago, I hypothesized that a symptom or condition is the result of a coming together of many small deviations in individual bacteria representation. There may be 10 different combination of bacteria with none overlapping causing a symptom. The inspiration for this was observing the literature and experience of people with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) — a sibling condition to Long COVID. This model is contrary to the common belief that there is a single or small number of items that is the cause. My looking at Brain fog (using same technique as above Brain Fog: Microbiome scents…) came up with nothing. That was not desired, but almost expected because that population is very heterogenous for cause with a long time since the triggering event for the microbiome to diverge from each other (often treatment attempts would be a factor). With long COVID, we have a short time since the triggering event and the people tend to be treatment naĂŻve, This makes finding patterns a lot easier (when you look under the right rocks!).

Almost everything is overproduction. This may be caused by the immune system ramping up to provide fuel to fight COVID. The microbiome is stuck in an on-state, likely with cross talk between enzymes keeping it stuck on. The term of the Pasteur Institute for Tropical Medicine, “an occult infection” describes the behavior seen nicely.

Addressing the few microbiome shifts is one approach — but the enzymes dominate in both statistical significance and number of items, It is likely the best path to address the enzymes instead of individual bacteria.

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Brain Fog: Microbiome scents…

At present in our citizen science database we have samples reporting brain fog for:

  • Biomesight: 124 samples
  • Ombre/Thryve: 151 samples
  • UBiome/Thryve: 170 samples

Results from different labs cannot be safely aggregated, so we will investigate on a lab by lab basis. One lab will read data as bacteria A and a different lab as bacteria B.

For very different and strong results using the same process see: Long COVID: microbiome scents – we smell a skunk!

Taxon Patterns

By bacteria found nothing common across labs.

BacteriaubiomeOmbreBiomeSight
FaecalibacteriumLow
SubdoligranulumLow
Hespellia High
PorphyromonasHigh
OscillibacterHigh
AnaerovibrioHigh
StreptococcusHigh
Only Genus were inspected that were frequently seen

End Product Patterns

Ubiome was nothing significant. As above, nothing was in common between the labs. End Products have been weak to predict in prior analysis.

End ProductuBiomeOmbreBiome Sight
Bacteriocin: (several)Less
DaidzeinLess
L-TryptophanLess
Gamma-Amino butyric acid (GABA)Less
UrolithinsLess
Pyruvic acidLess
MethanolLess
PentanolLess

KEGG Enzyme Patterns

ubiome gave 280 candidates, biomesight just 2, ombre had 40 candidates. There was nothing in common.

EnzymeuBiomeOmbreBiomeSight
(1->4)-alpha-D-galacturonan lyaseHigh
15-cis-phytoene:acceptor oxidoreductase (lycopene-forming)High
nitrous oxide:ferricytochrome-c oxidoreductaseHigh
CDP-choline phosphohydrolaseHigh

KEGG Product

Biomesight returned nothing, Ombre just 7 candidates and ubiome 23. There was nothing in common.

KEGG Substrate

Biomesight returned 2 candidates, Ombre returned 42 candidates and ubiome 86. There were a few things in common between Ombre and uBiome. False Detection rate is a risk.

Bottom Line

I am disappointed in not finding many associations. I will pass the torch to others to see if there is literature connecting these to coagulation or vascular constriction/dilatation .

A comment about Gluten Issues MISINFORMATION

Saying “gluten is bad for you” is the same as saying the “bacteria are bad for you” (or “vitamins are good for you”. In some cases bacteria can be good for you, i.e. probiotics. Some vitamins can be bad, for example, “Vitamin D Toxicity“[2022]. These are over simplification and sweeping generalizations. To me, they are akin to saying “Blacks are criminals”, “Irish are drunkards”, and “Italians are part of the Mafia”.

”Gluten is a complex mixture of hundreds of related but distinct proteins, mainly [in wheat] gliadin and glutenin. Similar storage proteins exist as secalin in rye, hordein in barley, and avenins in oats and are collectively referred to as “gluten.” ” What is gluten? (US National Library of Medicine)
Barley is free of glutenins and gliadins, the troublesome glutens. You may be using “All black men are criminals” reasoning. You really need to be tested for which types of gluten proteins you reactive to and not go for internet-legend that all glutens are bad.

YES – you may feel better eating gluten free, but the why is more likely to be a wheat allergy than gluten issue!

Looking at how the microbiome is influenced by barley, oats, rye, and wheat we see major differences –– which I ascribed to the chemical difference of the type of gluten in each. In most western diet, many items described as “Rye Bread” contain wheat, an example is below. People react to it and thus associate rye (the labelling) to problems.

An example, Barley increases Ruminococcus according to 3 studies while wheat decreases it. For Clostridium botulinum: Barley and wheat increases while rye decreases. While a gluten free diet is reported to decrease both of these bacteria.

Bottom Line

You really should be tested for each type of gluten (even if your diagnosis is celiac disease). Going completely gluten free may make correcting a microbiome dysfunction a lot harder. Less than 1% of the population has a medical need to go gluten free [2018]. It is well sold by influencers on the internet.

Gluten-free diets have soared in popularity in recent years. But, shunning gluten has no heart benefits for people without celiac disease, and it may mean consuming a diet lacking heart-healthy whole grains, according to the quarter-century study.”

Eating Gluten-Free Without a Medical Reason? WebMd,

A 2018 study lists the following risks of doing it without a proven medical need:

Potential Harms of a GFD
Deficiencies of micronutrients and fiber
Increases in fat content of foods
Hyperlipidemia
Hyperglycemia
Coronary artery disease
Increased financial costs
Social impairment or restrictions

GF has a higher frequency of osteopenia and osteoporosis than in controls has been reported [2014]

A 2021 study reports “the currently available gluten-free products in the market are generally known to be lower in proteins, vitamins, and minerals and to contain higher lipids, sugar, and salt compared to their gluten-containing counterparts….  Some studies have shown that commercialized gluten-free food products are often not gluten free. “

in Efficacy of Popular Diets Applied by Endurance Athletes on Sports Performance: Beneficial or Detrimental? A Narrative Review [2021] “when applied to non-celiac athletes, [Gluten Free] can create a large energy deficit and low energy availability, impairing both metabolic health and performance.” This is of especial concern when a symptom prior to going GF is tiredness.

“Beware of influencers!” Often they get big bucks for selling a concept to you!

New Feature: Over and Under Representation

No, I am not talking about voting politics in the US!

While doing an analysis, I went to the raw data to try to understand the sample. The result is the addition of a new section on the [Research Features] tab. Unlike most items, this is not directly actionable. An analogy:

You have gotten 100 used coins from the bank and proceeded to toss each one once. You would expect to get 50 heads and 50 tails. You got 20 heads and 80 tails. This means that these 100 coins have bias that is statistically significant. You do not know which are the problem (unfair) coins.

The same issue applied to vectors of the microbiome.

A reader had just emailed me that they have done another sample and it occur to me to view a time series of this person over time to see what this new report offers. The person reports some improvements following Dr. Artificial Intelligence suggestions. I included Dr. Jason Hawrelak rating on each for reference

Nov 21, 2021, Jason: 56%ile
March 15,2022, Jason: 95.6%
May 16, 2022, Jason: 89%ile
June 15, 2022, Jason: 89%ile

The biggest improvement with Dr. Jason Hawrelak was between the first two. KEGG Compounds went from being under produced for both high and low, to over on all subsequent ones. The pattern of over and under kept consistent until the very last one where bacteria edged into significance. I do have concerns with single digit Z-Scores, because of the false discovery rate.

What does Over Representation of Low Bacteria mean exactly? It means that the number of different bacteria types sitting below 10% was much higher than expected. It may imply a more diverse population with a lot of token representation.

What does Under Representation of High Bacteria mean exactly? It’s the flip side of above. The number of different bacteria types sitting above 90% was much lower than expected. It may imply a population without full representation.

WARNING: Do not assign undue significance to a change of z-score with the same sign.

On a personal note, seeing bacteria shift into significance from insignificance, looks like a good thing. It means that the prior microbiome has become disrupted. Our goal is to disrupt the stable dysfunctional microbiome causing symptoms.

Again, this is both an experimental feature AND it’s interpretation is not easy.