Medical Conditions: Links between Conditions

This builds on Medical Conditions with Microbiome Shifts from US National Library of Medicine page where the bacteria shifts for various conditions are summarized. The question often is asked, “Did my Asthma caused my depression?” or other mixtures.

If the US had a unified medical system recording information from birth until the grave, then such questions can be answered by some database queries by a skilled statistician. Unfortunately, that is not the case and access to such data is often challenging because of privacy laws.

There is an approach that may hint at answers. Look at the bacteria and direction of shifts reported for various conditions and see if there are good matches. For example, you have 10 of the shifts seen for being afraid of dogs and there are 15 shifts seen in people that are afraid of pets. You would appear to be 10/15 = 66% of the way to that other condition.

The challenge is sparse data. For some conditions we have had lots of microbiome studies and for others almost none. We can view it as shown below.

The more the bacteria are in common, the more likely you may drift from one condition to another — often added as a co-morbid condition.

Looking at this data is available on the Medical Conditions with Microbiome Shifts from US National Library of Medicine page

Clicking will take you to a page that lists the percentage overlap and show a visualization with arrows thickness reflecting the percentage overlap. Remember that many conditions also require DNA mutations to cause the condition. This is NOT predictive, merely a factor to consider.

At the top, you can pick a different condition, set the percentage association to show (the lower the amount, the more items will appear and you may get a very busy page). Or, go over to every thing on one page.

Looking at what could cause Asthma, we see the key contributors.

When you hover over the line, you will get more information, for example Chronic Lyme. We see that we only have 3 bacteria types/taxon listed for Chronic Lyme (at this time),

Looking at Sleep Apnea, we see more bacteria are known about it.

You must balance the number of bacteria (taxons) with the percentage. High taxon counts with high percentage are likely significant. The issue keeps coming down to few studies on microbiome shifts.

Note: The numbers and charts will change over time as more data is found and entered.

Endometriosis (infertility), Microbiome and COVID

The coordinator of a UK Long COVID group asked me to research and post on this topic. Endometriosis is one form of infertility that has a prevalence around 7%. When I checked the US National Library of Medicine for Endometriosis and microbiome, I found 88 studies most published in 2021 and later. It is a newly discovered association. I have added it to my PubMed Study page with bacteria listed here and a priori changes of diet to counter these shifts listed here.

I repeated searching the US National Library of Medicine for Endometriosis and microbiome for endometriosis and COVID. I found 66 studies — a volume that surprised me! A few studies that appear interesting:

From The effect of SARSCoV2 BNT162b2 vaccine on the symptoms of women with endometriosis.

Concurrence between Microbiome Shifts

From the database I compared shifts between COVID and endometriosis, with the shift in common shown below.

Tax NameTax RankShift
CoriobacteriaceaefamilyHigh
EnterobacteriaceaefamilyHigh
AtopobiumgenusHigh
BacteroidesgenusHigh
BifidobacteriumgenusHigh
BlautiagenusHigh
CampylobactergenusHigh
CandidagenusHigh
CorynebacteriumgenusHigh
DialistergenusLow
EscherichiagenusHigh
FaecalibacteriumgenusHigh
LachnospiragenusLow
LactobacillusgenusLow
OdoribactergenusLow
ParabacteroidesgenusHigh
ParaprevotellagenusLow
PrevotellagenusHigh
PseudomonasgenusHigh
RuminococcusgenusLow
ShigellagenusHigh
StreptococcusgenusHigh
EubacterialesorderLow
ActinobacteriaphylumHigh
FirmicutesphylumHigh
ProteobacteriaphylumHigh
VerrucomicrobiaphylumHigh

Can COVID cause Endometriosis

There is no clear evidence of that, but the table of common shifts implies that it is a reasonable hypothesis. Looking at numbers from Long COVID groups, you may see over representation (above the 7% expected). Endometriosis increased the odds (almost double) of getting COVID then seeing 14% of Long COVID population with Endometriosis could be explain by the increase risk of getting COVID.

On the brighter side, we now see that endometriosis has a significant microbiome dimension and thus treatment by microbiome manipulation becomes an option worth exploring.

Long COVID with Mast Cell Issues?

Backstory

I’m in my early thirties and I caught COVID in November 2022. I’ve had dizziness from the beginning which is slowly going away, shortness of breath which is going away, weakness and pains all across my body, numbness, and this general feeling of derealization. Some days it felt I couldn’t even walk up the stairs. After extensive testing it was revealed that i had EBV reactivated, toxic mold, and whatever damage was left from long COVID. The big symptom that I’m still dealing with to this day are some sort of MCAS presentation where when i eat high histamine foods, exercise, sauna, or go for too long of a walk my throat will get tight, which is pretty scary. I also get dizzier upon anaerobic exercise. 

For other analysis for Long COVID click here.

Analysis

We again see the typical pattern for Long COVID and ME/CFS. Over representation of the 0-9%ile. For more information see Background on using this approach

PercentileGenusSpecies
0 – 977101
10 – 192420
20 – 291618
30 – 391118
40 – 491227
50 – 591219
60 – 691512
70 – 79415
80 – 891319
90 – 991924

In this case we see a number of bacteria flagged as likely causes of the above.

RankBacteriaImportancePercentile
genusBacteroides495%ile
speciesBacteroides stercoris3.2100%ile
speciesPhocaeicola vulgatus394%ile
genusRuminococcus2.793%ile
genusMediterraneibacter2.299%ile
speciesRuminococcus gnavus2.299%ile
genusEscherichia2.299%ile
genusMitsuokella2.1100%ile
speciesMitsuokella multacida2100%ile
High Bacteria

Comparing to the COVID Literature

Going over to Understanding the Relationship of the Human Bacteriome with COVID-19 Severity and Recovery [2023] We see the following cited as being higher: Mediterraneibacter. And Gut microbiota and COVID‐19: A systematic review [2023] cites higher Bacteroides stercoris, Phocaeicola vulgatus, Ruminococcus, Ruminococcus gnavus, Escherichia. Interesting that Gut microbiota in COVID-19: new insights from inside [2023] cites that Mitsuokella decreases with recovery. Our hope is that we will see this drop with our suggestions – there is only one known reducer: Nicotine.

Looking at the standard quick health overviews, we see a massive number of bacteria of concerns. While many are of low count, they are much higher than usually seen. This is in agreement with the over representation of the 0-9%ile range.

We see similar red flags with Dr. Jason Hawrelak Recommendations

Going Forward

There are so many items of concern that most practitioners would really not know where to start. Fortunately, the Artificial Intelligence engine was built to handle such complexities. Doing the quick route, I clicked the “Just Give Me Suggestions” and then click on the more technical details which takes us over to the consensus report.

The Consensus Report is done using all possible modifiers, including antibiotics and prescription drugs (that we have information on their microbiome impact). The quick suggests auto-picks items commonly used in treating ME/CFS and Long COVID.

The top suggestions are high in antibiotics, which is atypical.

Getting antibiotic prescribed off-label is a challenge.

Reader’s Question: “Any idea how to go about getting those prescription antibiotics? “

Ideally, you can get your primary care physician to be willing to prescribe one of those above. It does not need to be the first one. If the physician suggests something not on the list, use the filter feature to see it estimated benefit. Negotiate. I attach an article on Long COVID from this week’s edition of New Scientist.

Some practitioners may be uncooperative — there are several alternative approaches.

  • Look for a naturopath or MD that deals with Lyme infections. It is unlikely that you have Lyme BUT the gut disruption will often result in some Lyme tests returning a false positive. Getting that positive, even a weak one, will rationalize to that practitioner the prescription of antibiotics. Some of those listed above are used by Lyme physicians.
  • The following are not recommended but people have reported doing these approaches:
    • If you live near the Mexican border, many of the antibiotics are available there without prescription.
    • See if you can order directly from Vet Supply shops
    • If you have friends travelling to Mexico (or India or many 3rd world countries), they could buy at local pharmacies and bring it home to you.
  • The best way is always under medical supervision!

How to explain to your MD on how these suggestions are computed?

We have been developing an Artificial Intelligence program based on the pattern of the 1972 MYCIN system developed by Stanford University in California. Unlike the popular AI systems based on machine learning or large language models (Chat GPT), we use Probabilistic Inductive Logic Programming with over a million facts manually curated from the U.S. National Library of Medicine.  

LInks to more information are in above quote

Not walking the Prescription Path

Fortunately, we also have some herbs and species listed near the top. These include the following

And a few specific probiotics

I have no financial interest in Custom Probiotics — they are just by far the cheapest per BCFU and advocate therapeutic dosages.

I would encourage you to look at the avoids and remove the high value items. See video below.

I would not be surprised if you have a Jarisch–Herxheimer reaction from some of the above. I usually advocate the Cecile Jadin approach which is to take one or two items at a time for up to 2 weeks and then rotate to other items. Start with a low dosage and slowly work up the dosage. This will usually reduce the risk of a strong herxheimer reaction. This approach reduces the risk of antibiotic (or equivalent) resistance happening. There will always be a bacteria mutations that will tolerate specific herbs, probiotics and antibiotics. The odds of the bacteria tolerating multiple substances is very low.

I would suggest doing the rotating suggestions for 8 weeks and then retest. Always use the same lab so comparisons are valid.

Video Walkthru

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 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.

The answers above describe my logic and thinking and is not intended to give advice to this person or any one. Always review with your knowledgeable medical professional.

Predicting Conditions from PubMed Studies

I have an extensive collection of bacteria shifts reported from Studies on the US National Library of Medicine Studies for some 91 different conditions.

My past practice has been to deem over 75%ile to be a match if the study reported high and below 25%ile if the study reported a low. I then compute the number of hits for all samples and determine each person’s percentile. I then look at the reported incidence of the condition and see if there is a likely match.

For example, the condition is seen in 5% of the population: one person is at 45%ile – thus unlikely; another person is at 95%ile – thus borderline; a last person is at 99%ile – thus likely.

These 25%ile and 75%ile were arbitrary numbers point out of the air. I dislike arbitrary numbers. This attempts to find better numbers supported by evidence.


The root problem is that the study typically reports that the average of people with a condition is statistically different from the control group. This means that the only clear fact is whether the sample of people with this condition is higher or lower than the control group. This cannot be applied to an individual because the average is the average of a population with a wide range of values reported.


I looked at current available data and picked Depression to use for some test runs. We have 298 samples that are annotated with depression, and 226 different bacteria-shifts from studies). We divide our population into those that annotated with depression and those that annotated their sample but did not include depression.

  • Ombre reports 166 of the 226 bacteria from studies
  • BiomeSight reports 147 of the 226 bacteria from studies
  • uBiome reported 154 of the 226 bacteria from studies

This implies that Ombre may produce the best results, uBiome with intermediate, and Biomesight the worst.

The method is easy, finding the number of matches per sample for with depression and without depression. Then get the ratio between them. If the percentage is below 100, then we have false positives. We want the numbers to be over 100%. After going through the numbers, I came up with 109% as being a good threshold.

My first run was aggregating all lab data. We see good discrimination using 6%ile/94%ile. This drops almost in half at 10%ile/90%ile and disappears at 40%ile/60%ile. Aggregating all samples together has usually resulted in reduced statistical significance.

PercentileWithWithoutRatio
11.281.14112%
22.552.31111%
33.703.39109%
44.894.44110%
56.055.54109%
67.136.57109%
78.127.63106%
89.258.75106%
910.329.80105%
1011.4110.80106%
1517.1116.48104%
1921.2920.75103%
2932.1631.58102%
3033.1132.70101%

The next runs are being lab specific:

  • Biomesight:
    • 78 with depression,
    • 637 without depression.
    • We use a criteria of a ratio of 109% or better, so 6%ile/94%ile
PercentileWithWithoutRatio
11.261.10115%
22.862.48115%
33.993.57112%
45.224.68111%
56.475.82111%
67.686.87112%
78.517.96107%
  • Ombre Labs:
    • 78 sampleswith depression,
    • 340 samples without depression

The results blew me away! I give a possible explanation below.

PercentileWithWithoutRatio
10.750.8786%
22.091.05199%
33.421.70202%
45.052.32217%
56.603.00220%
68.193.61227%
79.594.27225%
810.974.93222%
912.445.57223%
1014.056.20226%
1115.546.85227%
1217.047.57225%
1318.888.23229%
4874.2331.98232%

And going to the defunct uBiome:

  • With: 103 Samples
  • Without: 376 Samples

It looks like using 22%ile and 78%ile yields a 109% ration or better.

PercentileWithWithoutRatio
11.751.32132%
23.092.06150%
34.302.89149%
45.303.73142%
56.324.64136%
67.175.59128%
78.206.48127%
89.327.37126%
910.358.30125%
1011.199.20122%
1112.1710.18119%
1213.1211.11118%
1314.1312.01118%
1415.1412.91117%
1516.1313.83117%
1616.9714.76115%
1717.8215.74113%
1818.7616.63113%
1919.6417.52112%
2020.4318.45111%
2121.3619.44110%
2222.1620.35109%
2323.0021.28108%
2424.0022.31108%
2524.9323.24107%
2625.9224.18107%
uBiome

Why does Ombre Labs blow away other Labs?

First, you need to understand the back story read The taxonomy nightmare before Christmas…[2019]. There is NO STANDARDIZATION. Different labs use different reference libraries. I would speculate that the reference libraries typically used for studies on the US National Library of Medicine is much closer to the reference libraries used by Ombre than those used by Biomesight.

It could be roughly compared to the studies using metric Bolts. Ombre nuts are metric (cm) and thus fit well. Biomesight nuts are imperial (inches), they do not fit as well, and on occasion may need to be forced. That is the likely nuts and bolts of it.

What does this mean for Predictions using PubMed Studies?

At the simplest level it means that my criteria for matching is different for each lab.

  • High is over 60%ile and Low is under 40%ile for Ombre
  • High is over 94%ile and Low is under 6%ile for Biomesight
  • High is over 78%ile and Low is under 22%ile for uBiome
  • Other labs: High is over 94%ile and Low is under 6%ile for Biomesight

We ended up with the same best to worst order for labs as predicted at the start — except the differences is a lot larger than I expected. It will likely take a week for me to modify the build processes and have numbers on Microbiome Prescription updated.

What about to Shotgun analysis (Thorne, Xenogene)? Answer is simple, we need a lot more samples from both of them.

Testing Discrimination Performance

I charted the with versus without depression for various labs below to see how strong the discrimination was. The charts are below with uBiome showing the best discrimination. At higher percentiles, ubiome is 3-4x more likely to detect depression over a not depression.

This hints that we need to reduce the percentiles

More work to do…

Environment and the Microbiome – PM2.5 is BAD

After a Facebook post, the post got this message. This post is a fuller answer

I will skip over the obvious impact of fungi and mold in your environment (home, car, work) on the microbiome. Pollutants impacting the microbiome and the immune system in well documented in recent studies.

For one condition that has been studied, pollution has a life-long impact, even if the exposure was for a relatively short period of time.

What can you do to limit the adverse impact?

The first step is to monitor. Know where there is an issue. We use two monitors – one outside and one inside. If I was working in the office daily, I would also have one there. Possibly a fourth one for how I commute to work (for example mold in the car). The cost was not much (buying from aliexpress.us $26 each) – and this model has an internal rechargeable battery (ideal for the commute).

The second step is to take the data and do something with it. Some examples for inside:

  • Use air-filters to reduce particle matter (PM) levels
  • Use activate-carbon filters to reduce:
    • Formaldehyde (HCHO)
    • Total Volatile Organic Compounds (TVOC).
  • Use dehumidifier to reduce humidity (a factor for mold)
  • Be aware that new items delivered could off-gas!!
    • We use an external shed with an ozone generator to reduce organic compound / perfumes / smells. Ozone breaks down TVOC and HCHO quickly.

For outdoor and home location,

  • If you work outside, you may wish to wear a half or full face mask with a N-95 or P-100 filter (we use P-100 as our standard). The half face mask gives a tight seal to the face.
    • In our area during the winter, many people still burn wood — you can see it on the outside meter before you can smell it.
  • You may wish to check the seals on doors and windows. Replace or improve them to reduce air leakage (and also save heating bills!). In some cases, you may want to consider removable masking tape (“the blue stuff”) to improve the seal.
    • If your furnace has an external air intake, you may wish to add filters on the intake.
  • Because of past wildfire smoke issue, we added in the attic a fan with good HEPA Activated Carbon filter to give the house a positive air pressure when needed. I.e. Only filter air comes in and seals that would allow pollutants to leak in, now exits our filtered air.
Left end is the filter, the fan engine and then a vent into the house.
  • One of the best solution is to move to a location with good air quality. There are resources on line to evaluate locations. We used them extensively before our last move.

From AirNow

For the world https://waqi.info/ Australia is above

If you have the option or desired to move — be aware of sources of pollutants at proposed places. Do an in depth investigation of the patterns for the whole year. We have a petrochemical plant to the north and one to the south – but we have a west to east wind pattern and located in a north-south valley. We also look at flood risk and marsh lands — both are high mold and fungi risks.

That’s the long and the short of it:

  • Studies showing that it is important
  • Tools to monitor
  • Our experience reducing the impact on our microbiome.

MCAS and Long COVID – Some Questions

Hey Ken. At a talk last night by a functional med/environmental doc, she said that recent research has shown that 21% of the population has MCAS (Mast Cell Activation Syndrome). Apparently, she said, MCAS is finally being recognised by the medical profession. She went on to say that if someone with MCAS gets Covid, they almost always get Long COVID. Can you draw any conclusions between the microbiome and MCAS as you have with other conditions, and maybe relate it to your other research into Long Covid?

The joy of a citizen science site with lots of contributed data is that we can get informal insight. For more information about the probable bacteria involved see Multiple Chemical Sensitivity (MCS) – A Cause Found?

Q: Does 21% of the population has MCAS (Mast Cell Activation Syndrome)?

A: We have 336 samples annotated with MCAS or histamine issues out of 1747 annotated samples. That is 19.2%. Conclusion: We are in agreement with the research.

Q: if someone with MCAS gets COVID, they almost always get Long COVID?

A: This is a bit of a chicken and an egg question. People with CFS/ME gets MCAS. Looking at uploads prior to Long COVID appearing, we actually have 30.5% of all samples with MCS; 16.5% of samples with ME/CFS (104). The incidence of MCAS in this ME/CFS population was 58%.

We have 190 samples annotated with Long COVID but only 13 reporting MCAS. My conclusion is that all of the people she saw with MCAS were borderline ME/CFS or ME/CFS already. A likely correct statement is that someone with ME/CFS and MCAS is likely to get Long COVID. All that COVID is likely to do is to push the person further into the ME/CFS spectrum. We cannot separate Long COVID from ME/CFS.

Doing filtering of people with MCAS without ME/CFS and then Long COVID, we get a 6.4% incident rate. This suggests that MCAS without being comorbid with ME/CFS does not always get Long COVID.

Why Percentile at taxonomy rank is important

A reader asked:

Do you have a blog post where I can learn more about how percentile distribution of a 16s can give statistical insights ? You often mention the concept that a “good” sample has a even distribution…I’m trying to understand why so and what uneven distribution might mean etc 

The answer is statistics!!

At each taxonomy level (species, genus, family, etc) we can reasonably assume that the count of each bacteria taxonomy are independent of others of the same rank. There may be a little correlation (if A goes up, B goes up), but in general, not significant.

When we use percentile instead of percentage, we change the information about the bacteria in a uniform distribution. Suppose you have 120 dice. You roll all of them. You expect to have around 20 with 1, 20 with 2, 20 with 3, 20 with 4, 20 with 5 and 20 with 6.

If you get 40 dice with 1 and 2 dice with a 6, you are reasonable to suspect that the dice are biased or loaded.

Instead of a 6 sided die, we use a 10 sided die — 10%ile ranges. If the number in each 10%ile range are the same, then you can assume that the die is fair OR in our case, the microbiome is balanced. If you get a great difference in each 10%ile ranges, you suspect that the die is bias OR the microbiome is unbalanced (as in an unbalance die).

Where there is over or underrepresentation gives us hints as to where there may be an issue. It does not tell us what the issue is. It simply tells us that the microbiome is unbalanced and points us at subsets of bacteria worth examining.

Wait! There is More

A reader sent me this recent paper which appears to emphasis this issue for having a high count in the 0-9%ile for inflammatory conditions.

These observations suggest a general mechanism that underlies changes in diversity in perturbed gut environments and reveal taxon-independent markers of “dysbiosis” that may explain why widespread yet typically low-abundance members of healthy gut microbiomes can dominate under inflammatory conditions without any causal association with disease.

Metabolic independence drives gut microbial colonization and resilience in health and disease [2023]

The question of causal association not being found may be a matter of sample size being used and cross-interactions and cooperation between these “minor voices”. The paper data came from Fecal Matter Transplants data and is illuminating on why many FMT fail to persist.

Small intestinal bacterial overgrowth (SIBO)

This is a look at Small intestinal bacterial overgrowth (SIBO) from the aspect of the microbiome. Whatever is happening in the small intestine flows out of it and impacts downstream systems. Items that modifies any microbiome abnormalities will likely impact the small intestine.

This post is a parallel to my earlier post Multiple Chemical Sensitivity (MCS) – A Cause Found?. We will not assume anything. Just let the data speak.

We have 181 samples annotated with SIBO. Ombre Labs: 57, uBiome: 57 and Biomesight: 57.

Literature Review

I found one study that does a very good job

Association between Gut Dysbiosis and the Occurrence of SIBO, LIBO, SIFO and IMO [2023] states “Bacteria characteristic of small intestinal bacterial overgrowth include StreptococcusStaphylococcusBacteroides, and Lactobacillus. “

Microbiome Associations

We have two bacteria that are reported significant in at least 2 of the 3 labs:

  • Bacteroides caccae (species)
  • Holdemania (genus)

A total of 31 bacteria (P < 0.001) was flagged as being significant and added to our collection.

We then look at Percentile and found only Bifidobacterium adolescentis showing a significant shift.

The complete list is below. Note that almost everything is High with SIBO.

ShiftIstax_nametax_rank
HighFlavobacteriiaclass
HighBacteroidiaclass
HighSpongiibacteraceaefamily
HighLachnospiraceaefamily
HighBacteroidaceaefamily
HighFlavobacteriaceaefamily
HighRhodocyclaceaefamily
HighAnaerolineagenus
HighEthanoligenensgenus
HighTrabulsiellagenus
HighBacteroidesgenus
HighHyphomicrobiumgenus
HighMyroidesgenus
highHoldemaniagenus
HighPseudoflavonifractorgenus
HighAdlercreutziagenus
HighBacteroidalesorder
HighFlavobacterialesorder
HighOceanospirillalesorder
HighNitrosomonadalesorder
HighBifidobacterium thermophilumspecies
HighHyphomicrobium aestuariispecies
HighAnaerolinea thermolimosaspecies
HighThermodesulfovibrio thiophilusspecies
HighBacteroides sp. dnLKV9species
HighBacteroides sp. 35AE37species
HighBacteroides caccaespecies
HighAdlercreutzia equolifaciensspecies
HighBlautia obeumspecies
HighPseudoflavonifractor capillosusspecies
LowBifidobacterium adolescentisspecies

We have only one clear agreement with the literature: Bacteroides with a large number of species deemed significant.

Compounds Produced

SIBO is usually detected by breath tests. The question is whether the chemicals detected in the breath is associated with the compounds that bacteria produced. What we found is below. The top 4 product in this list are the likely suspect for the first stage. These likely contributed to the chemicals detected. In particular, N-Acyl-L-homoserine abundance is associated with “Over 50 Gram-negative bacteria species (including several pathogenic species) use AHLs as autoinducers and the means of their communication in Quorum sensing” In other words it is not the source, but sends signals to the source bacteria to release the chemicals detected on the breath.

Trying to “find” the specific bacteria is not practical

  • 📚4543 different bacteria produces Hydrogen (just click to see the list)
  • 📚3817 different bacteria produces Hydrogen Sulfide
  • 📚622 different bacteria produces Methane.
CompoundNamepercentileObs
Methylaminoacrylate C20255 – has NH2 and Hydrogen61.5129
Aminoacrylate C20253 – has NH2 and Hydrogen61.5129
D-Erythritol 1-phosphate C2129460.7134
N-Acyl-L-homoserine C18061 – a signaling molecule60.3126
2-O-[6-O-Octanoyl-alpha-D-glucopyranosyl-(1->6)-alpha-D-glucopyranosyl]-D-glycerate39.844
(2R,3R)-Dihydroflavonol38.667
6-Phospho-2-dehydro-D-gluconate36.941
p-Hydroxybenzyl alcohol34.856
4-Hydroxybenzaldehyde34.856

Bottom Line

I have made the bacteria found above available on the site under Research tab

The page resulting looks like this:

Person with SIBO

With results like shown below. Note that on the Add with have gluten-free and on the Remove: wheat, barley.

This applies ONLY to the sample selected. It is not a general suggestion for SIBO

ME/CFS with Multiple Chemical Sensitivity

This is a continuation of my last post looking at Multiple Chemical Sensitivity (MCS) – A Cause Found? This resulted in a set of bacteria identified that appear to be associated.
For other analysis of people with ME/CFS see this page

Backstory

After reading your blog for many many years I finally managed to get a microbiome sample done (Biomesight). I suffer from debilitating MCS (multiple chemical sensitivity), mold sensitivity, and associated CFS. I have been isolated at home for almost 20 years now. Pretty much unable to function in any way normally, because of these sensitivities.

I think it all started in early 2000 with food poisoning from a poorly cooked chicken, that had been left out warm for too long. After this chicken meal my body simple went haywire. My gut was so sensitive that even drinking just a glass of water produced something similar to an anaphylactic shock.

It took several months to subside, and for me to completely revamp my diet and figure out what few items I was able to eat.

My body feels toxic. Like I am being constantly poisoned. Main symptoms are severe bloating and gas, extreme irritability and mood changes, brain fog and lethargy, poor blood flow which leads to lactic acid buildup everywhere, narrowing of vision, sleepiness to the point I call it “coma sleep” (I would not
wake up from these even if the fire alarm went off). Tinnitus, also have muscle twitches and probably 20 other symptoms I forget.

Fast forward to today, my MCS is so bad that I cannot even read a book because the fumes from printed ink causes a reaction. My body feels toxic. Like I am being constantly poisoned.

Through the years I have spent all my available cash on trying everything I can think of. Herbs, treatments, devices, gadgets. I have found a handful of herbs and supplements that initially gave me relief, but after a few weeks always stop working. Never found a permanent solution. Always temporary, quickly followed by developing resistance.

I’ve been reading your blog for a long time, but because of the mental and physical lethargy, it took me this long to even manage a microbiome analysis.

Do you have any experience with MCS? I am fairly certain this is a microbiome issue, but I have no clue what to do, and all my attempts have been just shooting in the dark trying to see
if anything would stick.

Reader in Europe

Analysis

The typical ME/CFS pattern of over representation of 0-9%ile. This is in contrast to MCS where the cause appears to be over population of a few demanding bacteria. A “normal” microbiome will have all of the Percentile ranges being about the same number.

PercentileGenusSpecies
0 – 97297
10 – 192721
20 – 291311
30 – 391315
40 – 491016
50 – 591920
60 – 691519
70 – 79717
80 – 891116
90 – 99813

The likely to be important for the above shift is just a single bacteria family.

RankBacteriaImportance
genusRoseburia3.4
speciesRoseburia faecis2.5
Bacteria suspect of causing above shifts

Looking at the different Health Filters 🕵️

Going over to [Special Studies] / [ From Special Studies] we see the typical matches — which also matches his symptoms:

As a result of the MCS Research post, I went over to the [Research Features] tab and picked the new experimental item shown below.

The likely bacteria are pre-selected.

Remember that we are not dealing with a single bacteria causing the problem, rather different combinations of bacteria forming a “cartel”

Building Suggestions

To speed (and simplify) the process, we start with the ‘Just give me Suggestions’ on the profile tab. This build a consensus using:

While the MCS associated bacteria above would likely be included by this, we do a fifth set of suggestions by hand picking these and getting those suggestions.

The MCS specific suggestions are below:

And the avoid:

Going over to Consensus

On that page, we sort by Take Count from highest to lowest. Items with a count of 5 addresses all concerns. The top of the list are:

Filter and looking for “5”

The smallness of this list indicates the problem of trying to serve many masters / addressing different goals.

Flipping to Avoids (Sorting by Avoid Count), we find nothing that is all “5” with the 4’s including: Iron, Vitamin E, Vitamin A, Vitamin D.

Returning to MCS specific probiotics – we see some (bacillus subtilis, clostridium butyricum aka Miyarisan, and bifidobacterium longum bb536 ). None of these items appear in the [Only] Positive Impact commercial probiotics – indicating that while overall positive, there are some negative impacts).

Bottom Line

Hoping for probiotics solutions failed to find any strong candidates. In terms of prescription items, these antibiotics are the top suggestions neomycin and lymecycline . It is interesting to note “Neomycin is not absorbed from the gastrointestinal tract and has been used as a preventive measure”[wikipedia]; so it’s impact is confined to the microbiome. Lymecycline is a tetracycline which also include minocycline and doxycycline — two antibiotics often used by ME/CFS specialists.

Reader Feedback

It looks like there’s not much to do, except perhaps antibiotics.

I was once prescribed ciprofloxacin for a lung infection, and all my symptoms went away for a couple days. They returned after the cipro course was completed. Later I’ve learned this antibiotic is very dangerous. So not very interested to test that particular type again.

Thiamine B1 I’ve found through experimentation that it helps a bit, as well as resveratrol (both listed among the text and images). High protein diet also helps, which was also listed.

A few herbal antibiotics also help, so the killing part does work. In fact the antibiotic route has always
produced better results than the nutritional path. Well, at least the antibiotic route produces immediate
results. Perhaps the nutritional path produces more sustainable results though, if I could figure it out.

The Lymecycline I would certainly want to test. Have to figure that out also.

It is nice to get feedback that the suggestions and the person’s experience doing multiple random experiments agree. The stated goal of Microbiome Prescription is to give better suggestion than random suggestions off the internet or ad hoc trials suggested by MDs.

As a FYI, I have always been an advocate for Cecile Jadin approach for antibiotics, single course, a break, then a different antibiotic (preferable a different family).

Q: Suggestions for labs for fungi etc?

Xenogene – Enevia Health which tests for these

Or

Thorne Labs:   https://www.thorne.com/products/dp/gut-health-test

This is what is in their data file for a person (i.e. detected only)
"Eukaryota","Fungi","Ascomycota","Dothideomycetes","","","","","","","","","","0.001554","0.00052608","0.0014506","77.3"
"Eukaryota","Fungi","Ascomycota","Eurotiomycetes","","","","","","","","","","0.0006793","0.0017786","0.003532","2.5"
"Eukaryota","Fungi","Ascomycota","Leotiomycetes","","","","","","","","","","0.0006979","0","0.0003654","90"
"Eukaryota","Fungi","Ascomycota","Saccharomycetes","","","","","","","","","","0.01638","0.00071344","0.0019584","99.2"
"Eukaryota","Fungi","Ascomycota","Sordariomycetes","","","","","","","","","","0.001107","0.0016878","0.0034788","18.9"
"Eukaryota","Fungi","Basidiomycota","Agaricomycetes","","","","","","","","","","0.0003536","0.00054734","0.0017092","17.2"
"Eukaryota","Fungi","Basidiomycota","Exobasidiomycetes","","","","","","","","","","0.0001024","0","0.00034712","52.2"
"Eukaryota","Fungi","Basidiomycota","Malasseziomycetes","","","","","","","","","","0.0001582","0","0.00010162","73.3"
"Eukaryota","Fungi","Basidiomycota","Tremellomycetes","","","","","","","","","","0.0002047","0.00023646","0.000608","17.9"
"Eukaryota","Fungi","Basidiomycota","Ustilaginomycetes","","","","","","","","","","0.00008375","","",""
"Eukaryota","Metazoa","Chordata","Mammalia","","","","","","","","","","1.985","0.0042838","0.06166","99.5"

Multiple Chemical Sensitivity (MCS) – A Cause Found?

Time to Refresh What we know

A reader request with severe MCS motivated me to revisit Multiple Chemical Sensitivity (MCS) and literature on it. I am first going to recap my memory of what I know, a literature review, Last, analysis using data contributed to Microbiome Prescription – which did not find anything major beyond bacteria shifts that are statistically significant. We explore enzymes, products and substrates with no smoking guns found

There was a processing error — This post was revised

Long weekend tracing issue, made short. Some revisions to reduce running cost had a typo pointing one set of data (Substrate data for Samples) to the wrong lookup table to determine percentile. This has been corrected and the data audited to insure correctness.

I had mild MCS during one flare. It disappeared with remission.

Multiple Chemical Sensitivity (MCS) is not bronchial (breathing). There was a series of studies where the person was wearing a half-face mask breathing compressed air. Bringing a triggered close to the person (blind testing), trigger the response. My own wife lab results leaves a significant scent. She had a complete workup with Dave Berg, Hemex Lab and two weeks later she had a bad MCS reaction. About a week later, new blood work was sent. Everything was the same, except for a marker indicating very active coagulation. The marker had a short half-life around 2 hours. After she fully recovered, same test returned to normal. This hints at coagulation being part of the process.
We did find one effective treatment for shortening the duration of a MCS episode: Olestra (as in Olestra chips). This compound sucks chemicals out of tissues [2015] [2014]

– Ken Lassesen

I attended a talk today with the AAAS (I’m a member) and Memory Cells was discuss for some autoimmune conditions. It occurs to me that these are likely a factor. These cells become uber-sensitive to specific chemical compounds and have a lasting memory. In time they may die off, but not quickly.

Caution: this post is subject to revision. The findings to date are so significant that I am posting early.

The Current Literature

First a summary from a 2022 review – it covers a lot of territory… many quotes are below

Multiple Chemical Sensitivity (MCS), a condition also known as Chemical Sensitivity (CS), Chemical Intolerance (CI), Idiopathic Environmental Illness (IEI) and Toxicant Induced Loss of Tolerance (TILT), is an acquired multifactorial syndrome characterized by a recurrent set of debilitating symptoms. The symptoms of this controversial disorder are reported to be induced by environmental chemicals at doses far below those usually harmful to most persons. They involve a large spectrum of organ systems and typically disappear when the environmental chemicals are removed. However, no clear link has emerged among self-reported MCS symptoms and widely accepted objective measures of physiological dysfunction, and no clear dose-response relationship between exposure and symptom reactions has been observed. In addition, the underlying etiology and pathogenic processes of the disorder remain unknown and disputed, although biologic and psychologic hypotheses abound. It is currently debated whether MCS should be considered a clinical entity at all.

Multiple Chemical Sensitivity [2022]
  • “Not surprising, MCS is often juxtaposed to, and sometimes combined with, other diseases for which definitive diagnoses and explanations are also found wanting, including fibromyalgia (FM), Gulf War syndrome (GWS), chronic fatigue syndrome (CFS), sick building syndrome (SBS), and electromagnetic radiation exposure (ERE) [18,23,24,25,26,27,28,29,30,31,32].”
  • “An association was documented, however, between MCS and increased nasal airflow resistance, respiration rate, and heart rate.” [2021] Volatile chemicals can not only affect respiration, but can cause laryngeal symptoms which, in the extreme, can induce vocal cord dysfunction [82]. 
  • Changes in skin conductance were also seen in MCS patients but not in controls [193].
  • Compared to younger persons, those 65 years of age and older are less likely to identify themselves as chemically sensitive [88].
  • In accord with this concept, McKeown-Eyssen et al. [219] found, in a female cohort of 203 MCS cases and 162 controls, that the cases had higher levels of cytochrome P450 CYP2D6 (i.e., one of the most important enzymes involved in the metabolism of xenobiotics in the body) and n-acetyl transferase 2 (NAT2). More possible genes listed here.
  • Like the sick building syndrome [89], there is a remarkably higher prevalence in women than in men [16,18,21,90,91], with the percentage of women ranging from 60% to 88% [18,57,92,93,94]. 
Multiple Chemical Sensitivity – there may be many roads and also subsets

Microbiome and MCS

Almost every condition in the above chart has microbiome shifts associated with it. Exposure to mold also is known to cause microbiome shifts. There appears to be no published studies exploring this possibility. At this time we have 128 people (7.3%) who have annotated their samples with Multiple Chemical Sensitivity [uBiome: 55, Ombre:39, Biomesight 25] to Microbiome Prescription.A

Executing analysis by lab, we found only one taxon reported significant in two labs. Bacteroides clarus where people with MCS had 3x the count of people not reporting MCS [BiomeSight, uBiome]. The top items of significance are shown below. All of them have much higher counts in people with MCS.

SourceprobabilityTax_Nametax_rankwith MCSwithout
MCS
Obs
BiomeSightP < 0.001Anaerotruncusgenus33561834683
BiomeSightP < 0.001Anaerotruncus colihominisspecies32081743683
BiomeSightP < 0.001Bacteroides intestinalisspecies289802430396
ThryveP < 0.001Prevotella maculosaspecies273995733404
Average Counts out of a million

These have been added to the [Research] tab, as shown below.

Looking at KEGG Enzymes we have the strongest candidates below. Looking for any enzyme that is significant for 2 or more labs, we had only one: 5.3.1.15 D-lyxose aldose-ketose-isomerase (Biomesight and Thryve).

EnzymeNameECKEYSrcWithMeanWithoutMeanTScoreDF
7alpha-hydroxysteroid:NAD+ 7-oxidoreductase1.1.1.159BiomeSight1468124794.01657
acetyl-CoA:glycerone phosphate C-acetyltransferase2.3.1.245BiomeSight49551274443.56701
acetyl-CoA:heparan-alpha-D-glucosaminide N-acetyltransferase2.3.1.78BiomeSight2690993944.02671
alginate beta-D-mannuronate—uronate lyase4.2.2.3BiomeSight2693394724.02681
CTP:phosphoglutamine cytidylyltransferase2.7.7.103BiomeSight27471131563.97702
L-alanine:glyoxylate aminotransferase2.6.1.44uBiome1608320293.40309
NAD+:glycine ADP-D-ribosyltransferase (sulfide-adding)2.4.2.59BiomeSight48398261813.60699
phosphoenolpyruvate:glycerone phosphotransferase2.7.1.121BiomeSight68289418083.60702
sn-glycerol-1-phosphate:NAD(P)+ 2-oxidoreductase1.1.1.261BiomeSight29070114403.55700
Probability of being random is P < 0.001

Dropping by Lab and using Percentiles Only

Trying a different approach aggregating all of the data and using percentile ranking. This masks most of the differences between labs and gives us large sample size, We have a very actionable item: increase Bifidobacterium by taking Bifidobacterium probiotics.

tax_nametax_rankpercentileObs
Alistipes indistinctusspecies61.761
Anaerobutyricum halliispecies39.841
Bifidobacterialesorder37.7106
Bifidobacteriumgenus37.1122
Oscillospiraceae incertae sedisnorank63.141
Acidobacteriaphylum33.248
Butyricimonas faecihominisspecies61.243
Bifidobacteriaceaefamily37.4122
Collinsella aerofaciensspecies39.183
Phascolarctobacterium succinatutensspecies37.352
Hungateiclostridiaceaefamily61.445
Bacteria where Percentile Average above 60%ile or below 40%ile

KEGG Enzymes

Applying this to KEGG Enzymes, we have just one of concern that is high: EC3.2.1.46  galactosylceramidase, and a big 39 that are low indicating a deficiency of enzymes is likely

EnzymeNamepercentileobs
[2.7.1.85] ATP:cellobiose 6-phosphotransferase34.664
[4.1.1.31] phosphate:oxaloacetate carboxy-lyase (adding phosphate, phosphoenolpyruvate-forming)35.2122
[3.2.1.199] 6-sulfo-alpha-D-quinovosyl diacylglycerol 6-sulfo-D-quinovohydrolase36.161
[1.17.2.1] nicotinate:cytochrome 6-oxidoreductase (hydroxylating)36.763
[3.5.1.18] N-succinyl-LL-2,6-diaminoheptanedioate amidohydrolase37.9122
[2.7.1.211] protein-Npi-phospho-L-histidine:sucrose Npi-phosphotransferase38122
[1.2.1.99] 4-(gamma-L-glutamylamino)butanal:NAD(P)+ oxidoreductase38.163
[1.17.98.4] formate:[oxidized hydrogenase] oxidoreductase38.3121
[3.4.23.51]38.4117
[2.7.1.195] protein-Npi-phospho-L-histidine:2-O-alpha-mannopyranosyl-D-glycerate Npi-phosphotransferase38.494
[1.1.1.65] pyridoxine:NADP+ 4-oxidoreductase38.498
[2.1.1.172] S-adenosyl-L-methionine:16S rRNA (guanine1207-N2)-methyltransferase38.5120
[2.1.1.264] S-adenosyl-L-methionine:23S rRNA (guanine2069-N7)-methyltransferase38.6121
[3.5.1.32] N-benzoylamino-acid amidohydrolase38.763
[2.7.7.12] UDP-alpha-D-glucose:alpha-D-galactose-1-phosphate uridylyltransferase38.7122
[2.4.1.342] ADP-alpha-D-glucose:alpha-D-glucose-1-phosphate 4-alpha-D-glucosyltransferase (configuration-retaining)38.9121
[4.1.2.22] D-fructose-6-phosphate D-erythrose-4-phosphate-lyase (adding phosphate; acetyl-phosphate-forming)39122
[4.1.2.9] D-xylulose-5-phosphate D-glyceraldehyde-3-phosphate-lyase (adding phosphate; acetyl-phosphate-forming)39122
[3.2.1.122] alpha-maltose-6′-phosphate 6-phosphoglucohydrolase39122
[1.1.1.9] xylitol:NAD+ 2-oxidoreductase (D-xylulose-forming)39.183
[6.3.1.12] D-aspartate:[beta-GlcNAc-(1->4)-Mur2Ac(oyl-L-Ala-gamma-D-Glu-L-Lys-D-Ala-D-Ala)]n ligase (ADP-forming)39.2122
[4.1.2.40] D-tagatose 1,6-bisphosphate D-glyceraldehyde-3-phosphate-lyase (glycerone-phosphate-forming)39.2122
[3.7.1.12] cobalt-precorrin 5A acylhydrolase39.2122
[1.3.1.28] (2S,3S)-2,3-dihydro-2,3-dihydroxybenzoate:NAD+ oxidoreductase39.273
[5.3.1.26] D-galactose-6-phosphate aldose-ketose-isomerase39.3115
[2.7.1.19] ATP:D-ribulose-5-phosphate 1-phosphotransferase39.462
[2.7.1.208] protein-Npi-phospho-L-histidine:maltose Npi-phosphotransferase39.4122
[2.7.1.207] protein-Npi-phospho-L-histidine:lactose Npi-phosphotransferase39.4118
[3.2.1.185] beta-L-arabinofuranoside non-reducing end beta-L-arabinofuranosidase39.472
[1.1.1.130] 3-dehydro-L-gulonate:NAD(P)+ 2-oxidoreductase39.572
[3.2.1.85] 6-phospho-beta-D-galactoside 6-phosphogalactohydrolase39.5117
[5.1.1.10] amino-acid racemase39.7108
[3.2.1.10] oligosaccharide 6-alpha-glucohydrolase39.7122
[1.1.1.203] uronate:NAD+ 1-oxidoreductase39.761
[3.5.2.9] 5-oxo-L-proline amidohydrolase (ATP-hydrolysing)39.7120
[2.7.1.191] protein-Npi-phospho-L-histidine:D-mannose Npi-phosphotransferase39.8122
[4.2.1.30] glycerol hydro-lyase (3-hydroxypropanal-forming)39.864
[3.4.17.19] Carboxypeptidase Taq39.9122
[2.7.1.189] ATP:(S)-4,5-dihydroxypentane-2,3-dione 5-phosphotransferase39.972
[3.2.1.46] D-galactosyl-N-acylsphingosine galactohydrolase63.365
Enzymes where Percentile Average above 60%ile or below 40%ile

Compound Produced

This is reflected in compound produced. With D-Galactose being the only high – matching enzyme [3.2.1.46] D-galactosyl-N-acylsphingosine galactohydrolase above,

CPIDCompoundpercentileobs
924Ferrocytochrome36.963
22336Reduced hydrogenase38.3121
250Pyridoxal38.698
157674-(L-gamma-Glutamylamino)butanoate38.763
166992-O-(6-Phospho-alpha-mannosyl)-D-glycerate38.794
1113D-Galactose 6-phosphate39.2118
1962,3-Dihydroxybenzoate39.373
4575(4R,5S)-4,5,6-Trihydroxy-2,3-dioxohexanoate39.572
615Protein histidine39.6122
666LL-2,6-Diaminoheptanedioate39.7122
1097D-Tagatose 6-phosphate39.8115
20890D-Glucaro-1,5-lactone39.961
20889D-Galactaro-1,5-lactone39.961
124D-Galactose63.565

Compounds Consumed

As above for production and for bacteria, we have just one item with a high percentile and many with a low percentile.

CompoundNamepercentileObs
Galactosylceramide63.965
5-Oxoproline39.9120
Hydrogen selenide39.9122
3-Dehydro-L-gulonate39.972
Reduced riboflavin39.850
Protein N(pi)-phospho-L-histidine39.6122
5-Aminopentanoate39.6106
[SoxY protein]-S-disulfanyl-L-cysteine39.643
(L-Seryl)adenylate39.660
(2S,3S)-2,3-Dihydro-2,3-dihydroxybenzoate39.673
6-Phospho-beta-D-galactoside39.5117
Sucrose39.4122
Hippurate39.463
alpha-D-Galactose 1-phosphate39.4122
2-Hydroxy-3-keto-5-methylthiopentenyl-1-phosphate39.452
D-Galactose 6-phosphate39.3115
4-Aminobutyraldehyde39.347
D-Xylulose 5-phosphate39.1122
Benzene-1,2,4-triol3943
L-Arabinonate38.652
Pyridoxine38.698
Salicylate38.344
dTDP-4-acetamido-4,6-dideoxy-alpha-D-galactose38.360
Oxidized hydrogenase38.3121
3,4-Dihydroxyphenylacetate38.147
Thymine37.845
FMN-N5-peroxide37.845
FMN-N5-oxide37.845
Ferricytochrome37.463
Hexadecenoyl-[acyl-carrier protein]37.247
Protein lysine37.1120
2-O-(alpha-D-Glucopyranosyl)-D-glycerate37.154
L-Rhamnonate36.746
Geraniol36.449
4-(L-gamma-Glutamylamino)butanoate36.344
D-Glyceraldehyde35.660
3-Hydroxybenzoate35.341
(2R)-3-Sulfolactate34.143
D-Glucaro-1,4-lactone33.343
D-Galactaro-1,4-lactone33.343

Bottom Line

The is no obvious imbalance between compounds produced and consumed. Thus the best path is to use the bacteria identified at the start. A quick select has been added to the menus.

  • There are a few things that could be factors, for example D-Galactaro-1,4-lactone is 33.3%ile for consumption and 39.9%ile for production. Unfortunately, the microbiome is not a closed system and whether any surplus accumulates would be too speculative.
Example of the MCS pick page for a person with MCS.