Suggestions Conflicts

A reader messaged me the following concern

hi ken, what would you do if there’s a massive contradiction between most of the suggestions generated by the general consensus and the suggestions generated by your new “from special studies” biomesight algorithm

The first thing that I want to point out is the warning on that page.

The main issue you may be seeing is in the selection of bacteria. With the regular selection, you focus on extreme values, i.e. top 10%, outside of standard lab ranges, outside of reference ranges from Jason Hawrelak and others. The amount outside of the reference range is used to give a weight to each bacteria for the importance of shifting. Different algorithms are used with different approaches (we do not know what the ideal one is).

With the special studies, we up-ended the algorithm. We picked the bacteria based on a simple “if the amount is above or below the reference norm+/- twice the standard deviation of the mean for the reference population and then use the z-score as the weight (the statistical significance for this bacteria)”.

This change means that a bacteria that is at the 70%ile may be included in the selection (which is very unlikely with the the first methods), and this bacteria could have a very high weight (which is based on statistical significance and NOT the difference from a mile post). A Bacteria at the 99%ile will be totally ignored if it is not statistically significant for the condition.

Statistically, I prefer the special studies approach because we are using the statistical significance of the bacteria for the significance/weight for suggestions instead of the naïve assuming that being high or low is the cause.

Bottom Line

  • We pick bacteria based on statistical significance for a specific condition and not whether they are high or low in general
  • We give the bacteria a weight based on statistical significance for a specific condition and not the difference from a bound.

In theory, with the identical same bacteria and counts selected for two different conditions, you will get different suggestions because the weight assigned will be different since the weight is based on the statistical significance for the condition.

I well understand the confusion of some, the model being used is getting more advanced and handling more complexities.

Special Studies: Cold Extremities

This is a common symptom for both ME/CFS and Long COVID. 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. It does.

My default view is that this symptom is likely due to vesicular constriction/inflammation or “stick blood” (which contains many coagulation possibilities) resulting in low warming blood flow.

Study Populations:

SymptomReferenceStudy
Sleep: Unrefreshed Sleep108778
  • Bacteria Detected with z-score > 2.6: found 145 items, highest value was 12.6
  • Enzymes Detected with z-score > 2.6: found 170 items, highest value was 5.3
  • Compound Detected with z-score > 2.6: found No items

The highest z-scores above are more than most other symptoms. This indicates that the causes are more homogeneous bacteria shifts.

For those with uploaded microbiome

Interesting Significant Bacteria

All bacteria found significant had too low levels. The dominant genus is Prevotella with the P.Copri being usually 90% of the genus count in our reference, but only 14% of the genus count with Cold Extremities indicating that the shift is very species specific. Looking at Prevotella copri in isolation, we see the best documented ways of increasing it are: mediterranean diet, resveratrol (grape seed/polyphenols/red wine), berberine, navy bean,  Conjugated Linoleic Acid and linseed(flaxseed).

It is interesting to note that some of these are known to improve coagulation or reduces inflammation

BacteriaReference MeanStudyZ-Score
Prevotella copri (species)66900309012.6
Prevotella (genus)74698212937.6
Prevotellaceae (family)82172366086.1
Bifidobacterium kashiwanohense PV20-2 (strain)326785.9
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)317785.8
Sporolactobacillaceae (family)173585.7
Thermosediminibacterales (order)48185.7
Sporolactobacillus (genus)174605.5
Sporolactobacillus putidus (species)174605.5
Bifidobacterium gallicum (species)37847835.5
Lactiplantibacillus pentosus (species)123225.3
Phocaeicola coprocola (species)75846635

Interesting Enzymes

Most (99%) enzymes found significant had too low levels.

EnzymeReference MeanStudy MeanZ-Score
n/a (3.4.24.20)40165.3
2-acetylphloroglucinol C-acetyltransferase (2.3.1.272)182585.1
ATP:L-threonine O3-phosphotransferase (2.7.1.177)24165295

Bottom Line

In this study, one species shouts out as the cause by not being there Prevotella copri. I would really emphasis the items listed above as encouraging its growth.

It may be available “soon” as a probiotic, “The gut bacterium Prevotella copri (P. copri) has been shown to lower blood glucose levels in mice as well as in healthy humans, and is a promising candidate for a next generation probiotic aiming at prevention or treatment of obesity and type 2 diabetes.” [2021]

This article is an interesting read: The Strange Case of Prevotella copri: Dr. Jekyll or Mr. Hyde? Especially for those who think all bacteria can be classified as either good or bad.

In terms of retail probiotics suggested, the E.Coli probiotic, Symbioflor-2 is suggested.

To obtain a priori suggestions, go to https://microbiomeprescription.com/Library/CitizenScience

The a priori suggestions, shown below, contains the items for P. Copri cited above.

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Special Studies: Unrefreshing Sleep

This is a common symptom for both ME/CFS and Long COVID. 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. It does, but the degree of association (z-scores) are lower than prior special studies despite having a larger study population.

Study Populations:

SymptomReferenceStudy
Sleep: Unrefreshed Sleep1041107
  • Bacteria Detected with z-score > 2.6: found 139 items, highest value was 5.1
  • Enzymes Detected with z-score > 2.6: found 208 items, highest value was 5.2
  • Compound Detected with z-score > 2.6: found 1 items, highest value was 2.8 – effectively zero when false detection rate is considered.

The highest z-scores above are less than other symptoms despite larger sample size. This indicates that the causes are more diverse and thus less homogeneous bacteria shifts.

Location of this custom filter

Interesting Significant Bacteria

All bacteria found significant had too low levels.

Low Veillonella is reported in some studies associated with sleep issues with it’s consumption of lactic acid(lactate) being cited as a possible factor:

BacteriaReference MeanStudyZ-Score
Veillonella (genus)406322825.1
Actinobacillus (genus)3531334.9
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)3211004.8
Clostridium cellulovorans (species)40174.8
Bifidobacterium kashiwanohense PV20-2 (strain)3181004.8
Actinobacillus porcinus (species)184734.6
Thiobacillus thiophilus (species)85264.6

Interesting Enzymes

All enzymes found significant had too low levels.

EnzymeReference MeanLong COVID MeanZ-Score
(1->4)-alpha-D-galacturonan lyase (4.2.2.2)245310745.2
2-acetylphloroglucinol C-acetyltransferase (2.3.1.272)185614.6
phylloquinone:disulfide oxidoreductase (1.17.4.4)28154.6
[RNA] 5′-hydroxy-ribonucleotide-3′-[RNA fragment]-lyase (cyclicizing; [RNA fragment]-3′- nucleoside-2′,3′-cyclophosphate-forming and hydrolysing) (4.6.1.19)15966344.5
CMP-N-acetyl-beta-neuraminate:beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-R (2->3)-N-acetyl-alpha-neuraminyltransferase (configuration-inverting) (2.4.99.6)16826594.5
propane-1,3-diol:NAD+ 1-oxidoreductase (1.1.1.202)8111064.5
ATP:(Kdo)-lipid IVA 3-deoxy-alpha-D-manno-oct-2-ulopyranose 4-phosphotransferase (2.7.1.166)15916454.5

Bottom Line

The key take away is that lactate/lactic acid levels appears to be a significant contributor. The reason that it is high is the lack of lactate consumers. Removal of lactate producing probiotics from supplements appears to be a logical first step (i.e. Lactobacillus), followed by taking Vitamin B1 shortly before bed time.

For suggestions on lowering it, see this old post of mine in the ME/CFS context.

The issue may not be lactate by itself, but by the form of lactate (d-lactate –> bad)

Results and conclusion: Administration of L-lactate does not influence sleep-wake cycle of experimental animals. At the same time, its artificial optical analog D-lactate induces the significant (as compared to the control) decrease in wake (34.8% to 26.5%) and increase in slow wave sleep (57.4% to 69.2%). It has been suggested that D-lactate may be the antagonist of one or several L-lactate receptors.

[D-lactate as a novel somnogenic factor?] [2020]

“Thiamine (Vitamin B1) replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients.” [1997]

“Lactomin[300 mg Lactobacillus acidophilus, 300 mg Bifidobacterium longum] was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis ” [2010]

Phospholipids, the Microbiome and Mr. Hughes

For almost a decade I have suspected that there was an interaction between the microbiome and Antiphospholipid syndrome (APS) also known as Hughes Syndrome (after the MD, see below). This is also called  “sticky blood syndrome” [HealthLine]. For some researchers, it is deemed to be a significant contributor to fatigue in Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) [1999 D. Berg] and likely also applies to Long COVID. My own singleton experience seems to confirm it for myself.

A reader asked about phospholipids on Facebook today, so I revisited available literature

This article by Graham R.V. Hughes, MD, FRCP (the discoverer) in 2016 is well worth reading.

For me, APS/Hughes syndrome is very much a neurological condition. Brain function does seem to be especially targeted—the more APS patients one sees, the wider and wider the neuropsychiatric ripples spread.

APS: What Rheumatologists Should Know about Hughes Syndrome • By Graham R.V. Hughes, MD, FRCP

Of course, running off the experience of just one, or even a few people, is not the best practice. Testimonials suck because of rose color glasses, fake testimonials, mainly positive responders report, and placebo effects. So what does the literature state. First there is some literature that are general discussions without the type of detail that I would love to see:

Then we come to this article: Phosphatidylglycerols are induced by gut dysbiosis and inflammation, and favorably modulate adipose tissue remodeling in obesity [2019] which uses one of my favorite information source, the Kyoto Encyclopedia of Genes and Genomes. “We found that PGs were positively associated with microbiomes enriched with endotoxin-synthesis genes and associated with markers of inflammation.”

Digging further we find:

 Bacteroides thetaiotaomicron, Actinomyces massiliensis, Pseudopropionibacterium propionicum, Corynebacterium amycolatum, Ruminococcus gnavus and Roseburia intestinalis[2021] lead to the formation of pathogenic T‑cell and autoantibody responses via the cross-reactivity with autoantigens (Ro60, dsDNA and ß2 glycoprotein I). 

The role of the microbiome in lupus and antiphospholipid syndrome [2020]

M. pneumoniae and Streptococcus spp. infections, which are among the most prevalent bacterial infections in children and young adults, were linked to the occurrence of aPL. …. an anaerobic bacterium Fusobacterium necrophorum, although a variety of other bacteria such as streptococci, staphylococci, and enterococci may be also responsible…. a specific change in the gut microbial composition in APS patients. Particularly, a decrease of bacteria belonging to the genus Bilophila and overgrowth of bacteria of the Slackia genus were shown…  enrichment by Slackia spp. and by the lower abundance of butyrate-producing Butyricimonas 

Environmental Triggers of Autoreactive Responses: Induction of Antiphospholipid Antibody Formation [2019]

More discussion of mechanism is in The Role of the Gut Microbiota in the Pathogenesis of Antiphospholipid Syndrome [2015]

Bottom Line

APS only requires one of the bacteria above to trigger it. In terms of using Microbiome Prescription, I would look at Bilophila and Butyricimonas – if below 50%ile, hand pick it, then look at Slackia, if above 50%ile then hand pick it. Check the other bacteria cited above, and if any are over 75%ile, hand pick those. “It only takes one rotten apple to spoil the barrel” seems to apply here.

I have added APS to my PubMed reference list:

Personal Observations

I checked my samples from my last ME/CFS flare and found that Bacteroides thetaiotaomicron went from 73%ile on first sample after onset, to 96%ile on second sample, down to 79%ile, then 70%ile then 20%ile a few months later with recovery and returning to work. The key triggering bacteria will likely be different for each person but you at least have a candidate list to work from.

Same old, same old — Microbiome will stay Stuck!

For items like antibiotics and probiotics, I have for a long time been a strong advocated for continuous rotation. The original source for this attitude was Cecil Jadin’s treatment protocol for occult rickettsia (which originated with the Pasteur Institute for Tropical Medicine). This was followed by reading studies finding that rotating or even just pulsing (2 weeks on/ 2 weeks off) was more effective in reducing bacteria than continuous. Probiotics often function via the natural antibiotics they produce (a lot of prescription antibiotics originated with bacteria); hence probiotic rotation became part of my preaching.

If you have microbiome related issues, my soapbox has been “your goal is make the stable dysfunctional microbiome, unstable. Today I read a study on Nature that further clarifies what may be needed.

Together, these findings suggest that the human gut microbiome’s metabolic potential reflects dietary exposures over preceding days and changes within hours of exposure to a novel nutrient. The dynamics of this ecological memory also highlight the potential for intra-individual microbiome variation to affect the design and interpretation of interventions involving the gut microbiome.

Ecological memory of prior nutrient exposure in the human gut microbiome [2022]

If the goal is to make the microbiome unstable, then this gives some clear indication of strategy.

  • Every two weeks change the dominant starch – for example, if pasta is a regular meal item then
    • Made from glucomannan—a starch found in the konjac yam/ Konjac Flour (Source)
    • Made from red lentils and quinoa (Source)
    • Made from white rice flour, organic amaranth flour (Source)
    • Made from chickpea flour, organic yellow lentil flour, organic red lentil flour, organic kale powder, organic spinach powder (source)
  • Every two weeks change dominant proteins source
    • Fish
    • Pork
    • Lamb
    • Duck
    • Chicken
    • Turkey
  • Change vegetables and fruit too…
  • Change main spices used….

The key aspect is that every new addition results in a change of the microbiome. If you have microbiome issues, that is what you want to do. You do NOT want to take the same supplements, herbs, spices, vitamin or comfort food – continuously. You want to shake things up!

Approaching Small intestinal bacterial overgrowth (SIBO) from “the other end”

While the location of SIBO and the results of a stool test are a good physical distance apart, as part of an ongoing series of posts on special studies, I ran SIBO thru this morning — really expecting to find nothing, or perhaps a few overgrowths. To my surprise, the results was significant undergrowth with high statistical significance!

A formal post on the results is in the queue, but I thought that I should make the results available for those who wish to commit SIBO heresy!

On the [Changing Microbiome] tab

SIBO reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. A summary table of various studies has been added there which shows the statistical association is actually pretty strong.

Of course, you are saying “but this is down stream how can it impact upstream?!!?” To me, it is like saying, “I was waiting in a queue and everyone is healthy except the first person in the queue who had COVID, how could I get it?” Bacteria spread, including upstream.

 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.  A few items of special interest are:

BacteriaReference MeanStudy
Shuttleworthia (genus)27333
Prevotella stercorea (species)637831
Coprococcus eutactus (species)79871463
Streptococcaceae (family)35671473
Veillonellaceae (family)1729510944
Tissierellales (order)41621457
Peptoniphilaceae (family)41581456

In terms of enzymes, the four items that were most significant were all low levels of:

Bottom Line

SIBO by definition is OVERGROWTH, the stool samples and statistics says it is an UNDERGROWTH condition. Undergrowth means that substances do not get processed fully….

The sample size is low, more people with SIBO should transfer their data to Biomesight, then back to Microbiome Prescription, and then annotate it with SIBO. See Video on Transferring Data from Ombre/Thryve to Biomesight and then to Microbiome Prescription. I will wait until the sample size is larger before doing a formal post.

In the mean while, people with SIBO can try the new algorithm on the changing microbiome page. Feel free to add comments here on experience after trying suggestions for a month.

REMEMBER: The usual test is finding various compounds on the breath. Are the compounds from producing too much(overgrowth) or the compounds are not being consumed enough (undergrowth). Both scenarios produce a positive result. It feels like someone jumped to a conclusion and this arbitrary decision stuck in the name.

Special Studies: Bloating

This is a common symptom for people that have uploaded. 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 (A summary table of various studies has been added there).

Study Populations:

SymptomReferenceStudy
Bloating105198
  • Bacteria Detected with z-score > 2.6: found 120 items, highest value was 5.4
  • Enzymes Detected with z-score > 2.6: found 298 items, highest value was 5.4
  • Compound Detected with z-score > 2.6: found ZERO items

The highest z-scores above are less than other symptoms with smaller study sizes. The likely cause is a more diverse study population

Interesting Significant Bacteria

All bacteria found significant had too low levels.

The dominant bacteria group seems to be Bifidobacterium, low Bifidobacterium . The latter we know little about. 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.

BacteriaReference MeanStudyZ-Score
Bifidobacterium cuniculi (species)82285.4
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)320865.4
Bifidobacterium kashiwanohense PV20-2 (strain)316865.3
Veillonella (genus)405421965
Bifidobacterium asteroides (species)58265
Haemophilus parahaemolyticus (species)68224.9
Lactiplantibacillus pentosus (species)120274.9
Bifidobacterium animalis (species)12211604.7
Bifidobacterium gallicum (species)378511114.7

Interesting Enzymes

All enzymes found significant had too low levels.

I will leave it to the reader to go to Kyoto Encyclopedia of Genes and Genomes to learn about these enzymes (a steep learning curve).

EnzymeReference MeanStudy
Mean
Z-Score
D-glucose-6-phosphate:NAD+ 1-oxidoreductase (1.1.1.388)79165.4
2-acetylphloroglucinol C-acetyltransferase (2.3.1.272)184605
ornithine lipid,2-oxoglutarate:oxygen oxidoreductase (ester-linked acyl 2-hydroxylase) (1.14.11.58)81195
L-tyrosine:D-ribulose-5-phosphate lyase (isonitrile-forming) (4.1.99.24)104385
ATP:L-threonine O3-phosphotransferase (2.7.1.177)24456134.9
L-pipecolate/L-proline:NADP+ 2-oxidoreductase (1.5.1.21)183554.9

Bottom Line

The absence of Bifidobacterium is echo in several studies

REMEMBER: With your appropriate 16s sample, Dr. Artificial Intelligence on Microbiome Prescription will detail out foods, supplements et cetra to take (and to AVOID). If you do not have a sample, then review Bifidobacterium Summary Page.

Special Studies: Post-Exertional Malaise (PEM)

This is a common symptom for both ME/CFS and Long COVID. 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.

Beyond the goal of identifying bacteria involved, I am curious on the intersection of the bacteria with ME/CFS and Long COVID – i.e. bacteria in common and not in common.

Study Populations:

SymptomReferenceStudy
Post-Exertional Malaise (PEM)108662
  • Bacteria Detected with z-score > 2.6: found 181 items, highest value was 6.2
  • Enzymes Detected with z-score > 2.6: found 237 items, highest value was 7.0
  • Compound Detected with z-score > 2.6: found ZERO items

The highest z-scores above are less than other symptoms. There are two possible reasons:

  • Smaller Study Population
  • A more varied population in the study group.

Interesting Significant Bacteria

All bacteria found significant had too low levels.

We have two dominant bacteria group, both Bifidobacterium and Sporolactobacillus. The latter we know little about. 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.

Bacteria (Rank)Reference MeanStudy Meanz-score
Sporolactobacillus (genus)174606.2
Sporolactobacillus putidus (species)174606.2
Sporolactobacillaceae (family)173606.2
Bifidobacterium cuniculi (species)81245.9
Bifidobacterium asteroides (species)58235.9
[Ruminococcus] gnavus (species)742133365.4
Mediterraneibacter (genus)787037175.3

Interesting Enzymes

All enzymes found significant had too low levels.

I will leave it to the reader to go to Kyoto Encyclopedia of Genes and Genomes to learn about these enzymes (a steep learning curve).

There are some items of special interest appearing which I drill into below.

EnzymeZ-Score
hydrogen-sulfide:ferredoxin oxidoreductase (1.8.7.1)7
D-fructose:ubiquinone 5-oxidoreductase (1.1.5.14)6.2
D-fructosyl-L-lysine 3-epimerase (5.1.3.41)6.1
L-tryptophan carboxy-lyase (4.1.1.105)6
aromatic-L-amino-acid carboxy-lyase (4.1.1.28)6
CTP:N-acylneuraminate cytidylyltransferase (2.7.7.43)5.9
protein-Npi-phospho-L-histidine:L-ascorbate Npi-phosphotransferase (2.7.1.194)5.8
propane-1,2-diol hydro-lyase (propanal-forming) (4.2.1.28)5.7
N-methylhydantoin amidohydrolase (ATP-hydrolysing) (3.5.2.14)5.5
D-ribopyranose furanomutase (5.4.99.62)5.5
3-dehydro-L-gulonate:NAD(P)+ 2-oxidoreductase (1.1.1.130)5.5

hydrogen-sulfide:ferredoxin oxidoreductase (1.8.7.1): This is connected to iron. The blood uses iron to carry oxygen, and thus an absence/low level could [speculation] result in an impact on the blood’s ability to deliver oxygen (thus fatigue).

D-fructose:ubiquinone 5-oxidoreductase (1.1.5.14): This is also connected to iron.

For those wishing to explore more, you may wish to read Oxidoreductase

It does hint at an experiment to try: After exercise, try a dosage of Ubiquinol to see if it influences things.

Common Bacteria Shifts Observed in ME/CFS

We have 45 bacteria in common, they are listed below. A LOT of them are bifidobacterium, and no lactobacillus. This implies that bifidobacterium probiotics may be a good choice for ME/CFS with PEM

Tax_NameTax_rank
Thiorhodococcus pfennigiispecies
Candidatus Tammella caduceiaespecies
Veillonella atypicaspecies
Tammellagenus
Myxococcalesorder
Gemella cuniculispecies
Bifidobacterium catenulatumspecies
Nannocystineaesuborder
Olivibactergenus
Campylobacteralesorder
Epsilonproteobacteriaclass
Campylobacteraceaefamily
Pedobacter kwangyangensisspecies
Haemophilus parainfluenzaespecies
Haemophilusgenus
Clostridium aestuariispecies
Sterolibacteriaceaefamily
Lactococcus fujiensisspecies
Bifidobacterium bifidumspecies
Atopobiumgenus
Balneolagenus
Balneola vulgarisspecies
Balneolaceaefamily
Thiobacillusgenus
Pigmentiphagagenus
Thiobacillaceaefamily
Balneoliaclass
Balneolalesorder
Balneolaeotaphylum
Ruminococcus flavefaciensspecies
Hydrogenophilaliaclass
Hydrogenophilalesorder
Hydrogenophilaceaefamily
Atopobiaceaefamily
Veillonella disparspecies
Veillonellagenus
Clostridium chartatabidumspecies
Actinobacillus pleuropneumoniaespecies
Sporolactobacillaceaefamily
Sporolactobacillus putidusspecies
Sporolactobacillusgenus
Bifidobacterium kashiwanohense PV20-2strain
Bifidobacterium catenulatum subsp. kashiwanohensesubspecies
Bifidobacterium gallicumspecies
Bifidobacterium cuniculispecies
Bacteria COMMON to ME/CFS and PEM

Common Bacteria Shifts Observed in Long COVID

We have 42 bacteria in common, they are listed below. We notice some interesting difference from above:

  • Lactobacillus at the genus level as well as the retail probiotic Lactiplantibacillus plantarum (AKA Lactobacillus plantarum)
  • Bifidobacterium is still there, but one of them is available as a retail probiotics.
    • Bifidobacterium animalis
Tax_NameTax_rank
Paenibacillusgenus
Veillonellagenus
Actinomycetaceaefamily
Lactiplantibacillus plantarumspecies
Actinomycesgenus
Flammeovirgagenus
Flammeovirga pacificaspecies
Flammeovirgaceaefamily
Lactiplantibacillusgenus
Phocaeicola massiliensisspecies
Prosthecobactergenus
Fusobacterium gonidiaformansspecies
Candidatus Tammella caduceiaespecies
Gammaproteobacteriaclass
Tammellagenus
Coriobacteriaceaefamily
Fusobacteriaphylum
Fusobacteriiaclass
Fusobacterialesorder
Coriobacterialesorder
Bifidobacterium thermophilumspecies
Dolichospermum curvumspecies
Blautia wexleraespecies
Atopobiaceaefamily
Actinobacillus pleuropneumoniaespecies
Eggerthella lentaspecies
Fusobacteriaceaefamily
Atopobiumgenus
Schaaliagenus
Bifidobacterium gallicumspecies
Eggerthellagenus
Bifidobacterium animalisspecies
Aerococcaceaefamily
Coriobacteriiaclass
Bifidobacterium cuniculispecies
Schaalia naturaespecies
Phocaeicola sartoriispecies
Leptospira licerasiaespecies
Leptospiraceaefamily
Leptospiragenus
Leptospiralesorder
Alkalibacteriumgenus

Bottom Line

There appear to be differences between ME/CFS with PEM and Long COVID with PEM. The main difference is with Long COVID: Lactobacillus probiotics is a suggestion; for ME/CFS it is not.

Remember suggestions that are specific to your unique microbiome are available on the Microbiome Prescription web site.

Special Studies: Tinnitus (ringing in ear)

Tinnitus is not usually viewed as a microbiome issue. It was worth checking if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It did, hence this post

Study Populations:

SymptomReferenceStudy
Neurological-Audio:Tinnitus (ringing in ear)107573
  • Bacteria Detected with z-score > 2.6: found 129 items, highest value was 6.3
  • Enzymes Detected with z-score > 2.6: found 493 items, highest value was 7.1
  • Compound Detected with z-score > 2.6: found ZERO items

This is similar to Special Study: Histamine or Mast Cell Issues in finding no compounds, but the bacteria factor appears weaker and the enzymes is more.

Interesting Significant Bacteria

We have two dominant items that may be addressed by probiotics: Low Bifidobacterium and Low E.Coli

  • E.Coli probiotics are Symbioflor-2 and Mutaflor.
  • Bifidobacterium probiotics: we have 4 in the top group. Unfortunately none of these species are available at the retail level (that I am aware of). Checking interactions for these 4, there was no significant interactions found with common retail bifidobacterium species, just with the general genus.

Looking at Lactobacillus taiwanensis, there is a solid positive association with Bifidobacterium cuniculi and a weaker association with Bifidobacterium catenulatum subsp. kashiwanohense. There is also a weak association with two retail probiotic species: Bifidobacterium bifidum and Bifidobacterium animalis. It was interesting to note that there was no associations with any retail Lactobacillus species.

Bottom line appears to become: E.Coli probiotics, Bifidobacterium bifidum and Bifidobacterium animalis

All of the significant bacteria has too low levels.

BacteriaReference MeanStudyZ-Score
Bifidobacterium gallicum (species)37545346.3
Prevotella stercorea (species)66141026
Bifidobacterium subtile (species)82325.3
Escherichia coli (species)7161705.3
Lactobacillus taiwanensis (species)85125.3
Catenibacterium mitsuokai (species)432345.2
Bifidobacterium cuniculi (species)81285.1
Enterobacteriaceae (family)894826225
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)313715

Interesting Enzymes

As above, all levels that were found significant had too little. I will leave it to the reader to go to Kyoto Encyclopedia of Genes and Genomes to learn about these enzymes (a steep learning curve).

EnzymeReference MeanStudy
Mean
Z-Score
[cysteine desulfurase]-S-sulfanyl-L-cysteine:[molybdopterin-synthase sulfur-carrier protein]-Gly-Gly sulfurtransferase (2.8.1.11)532620437.1
gamma-L-glutamyl-L-cysteinyl-glycine:spermidine amidase (3.5.1.78)321210666.3
gamma-L-glutamyl-L-cysteinyl-glycine:spermidine ligase (ADP-forming) [spermidine is numbered so that atom N-1 is in the amino group of the aminopropyl part of the molecule] (6.3.1.8)321210666.3
tRNA-uridine13 uracil mutase (5.4.99.27)367112466.3
donor:hydrogen-peroxide oxidoreductase (1.11.1.21)30528696.2
S-adenosyl-L-methionine:tRNA 5-(aminomethyl)-2-thiouridylate N-methyltransferase (2.1.1.61)368613056.1
5-oxo-L-proline amidohydrolase (ATP-hydrolysing) (3.5.2.9)1018035056.1
thioredoxin:protein disulfide oxidoreductase (dithiol-forming) (1.8.4.16)381213016.1
acetyl-CoA:N6-hydroxy-L-lysine 6-acetyltransferase (2.3.1.102)7191436.1
UDP-alpha-D-glucose:enterobactin 5′-C-beta-D-glucosyltransferase (configuration-inverting) (2.4.1.369)8191416.1
S-adenosyl-L-methionine:tRNA (uracil54-C5)-methyltransferase (2.1.1.35)381712736.1
L-methionine:2-oxo-acid aminotransferase (2.6.1.88)27718156.1

Interesting Compounds

Nothing was found again!!!! In one sense this was a surprise, in another sense, it hints that the results found significant are not random.

Bottom Line

This was an interesting analysis because the dominant deficiencies were in genus that are available as probiotics. In reality, it points to just 3 probiotics: an E.Coli probiotic and two bifidobacterium. Food suggestions will be generated on Microbiome Prescription using an individual’s unique microbiome.

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From The Gut Club: Stool Test Discussion Group

I went and looked at these two in combinations and got a lot of bacteria in common

Bacteria NameTaxonomy rank
Nostocgenus
Citrobactergenus
Anaerococcus lactolyticusspecies
Streptomycetalesorder
Negativicoccus succinicivoransspecies
Sutterella stercoricanisspecies
Streptomycetaceaefamily
Negativicoccusgenus
Lactococcus fujiensisspecies
Actinomycetaceaefamily
Prevotella disiensspecies
Prosthecobactergenus
Clostridium chartatabidumspecies
Olivibactergenus
Peptoniphilus asaccharolyticusspecies
Butyricimonas synergisticaspecies
Campylobacteralesorder
Epsilonproteobacteriaclass
Campylobacteraceaefamily
Pedobacter kwangyangensisspecies
Staphylococcus pseudolugdunensisspecies
Enterobacteralesorder
Streptococcus millerispecies
Schaaliagenus
Enterobacteriaceaefamily
Mitsuokellagenus
Gammaproteobacteriaclass
Prevotellaceaefamily
Clostridium cellulovoransspecies
Schaalia naturaespecies
Enterobacteriaceae incertae sedisnorank
Blochmanniagenus
Bulleidiagenus
Bifidobacterium cuniculispecies
Prevotellagenus
Escherichiagenus
Prevotella coprispecies
Bifidobacterium gallicumspecies
Escherichia colispecies
Prevotella stercoreaspecies
Prevotella paludivivensspecies
ProForma Suggestions

Special Study: Histamine or Mast Cell Issues

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.

Suggestions are available on Changing Microbiome tab on https://microbiomeprescription.com/

Study Populations:

SymptomReferenceStudy
Histamine or Mast Cell Issues109256
  • Bacteria Detected with z-score > 2.6: found 143 items, highest value was 8.5
  • Enzymes Detected with z-score > 2.6: found 215 items, highest value was 6.1
  • Compound Detected with z-score > 2.6: found ZERO items

Interesting Significant Bacteria

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

BacteriaReference MeanStudyZ-Score
Prevotella paludivivens (species)140218.5
Prevotella stercorea (species)6451456.1
Escherichia albertii (species)9122325.1
Serratia (genus)10112754.9
Serratia entomophila (species)9872634.8
Alishewanella (genus)35194.7
Clostridium cellulovorans (species)40174.6
Yersiniaceae (family)10323174.6
Prevotellaceae (family)81953287334.5
Prevotella copri (species)65645139944.5
Escherichia (genus)561716644.5
Prevotella (genus)73889227714.5
Staphylococcus pseudolugdunensis (species)45204.3
Escherichia coli (species)7122344.3
Schaalia naturae (species)211374.3
Atopobiaceae (family)132394.2
Rhodovibrionaceae (family)119614.1
Bulleidia (genus)188304.1

Interesting Enzymes

As above, too low levels were most significant

EnzymeReference MeanStudy
Mean
Z-Score
propanoyl-CoA:oxaloacetate C-propanoyltransferase (thioester-hydrolysing, 1-carboxyethyl-forming) (2.3.3.5)14433806.1
(2S,3R)-3-hydroxybutane-1,2,3-tricarboxylate pyruvate-lyase (succinate-forming) (4.1.3.30)13953835.8
S-methyl-5′-thioadenosine:phosphate S-methyl-5-thio-alpha-D-ribosyl-transferase (2.4.2.28)365415175.4
UDP-N-acetyl-alpha-D-glucosamine:lipopolysaccharide N-acetyl-D-glucosaminyltransferase (2.4.1.56)10082645.2
(2S,3S)-2-hydroxybutane-1,2,3-tricarboxylate hydro-lyase [(Z)-but-2-ene-1,2,3-tricarboxylate-forming] (4.2.1.79)12464015.2
n/a (3.4.23.49)12443565.1
L-carnitinyl-CoA hydro-lyase [(E)-4-(trimethylammonio)but-2-enoyl-CoA-forming] (4.2.1.149)13803675
acyl-CoA,ferrocytochrome b5:oxygen oxidoreductase (6,7 cis-dehydrogenating) (1.14.19.3)10133025

Interesting Compounds

Nothing was found!!!! In one sense this was a surprise, in another sense, it hints that the results found significant are not random.

Bottom Line

Histamine or Mast Cell Issues appears to a condition of deficiency. Common internet thinking is that it is a condition of a surplus of histamine producing bacteria. It is more likely that the normal histamine consumers are being starved of enzymes that are needed to stop the accumulation of histamine.

Proforma Suggestions