Experiment with Kefir

A reader asked to look at the data from an experiment she did.

I have provided two biomesight results from biomesight (BS) to microbiome prescription (MP). The sample consuming kefir daily was sent first (both to BS and MP). The second sample was after stopping kefir consumption between the two samples.

This was not the ideal sequence, getting a sample before doing Kefir and one after would be the typical approach. This approach should indicate what is lost by stopping. There was 3 weeks washout time before samples.

Analysis

The stopped Kefir sample is higher quality, so the expectation would be for the numbers to be higher. This is not the case. Stopping resulted in more extreme ranges for bacteria(1.5x more), less types of bacteria, dramatic drop in the count of bacteria out of range (93% decrease in Outside Lab Range). There was a significant in compounds being produced by the microbiome that were more extreme (8x increase) and enzymes also (3.6x increase).

CriteriaOn KefirStopped Kefir
Lab Read Quality3.95.3
Bacteria Reported By Lab470404
Bacteria Over 99%ile110
Bacteria Over 95%ile305
Bacteria Over 90%ile4319
Bacteria Under 10%ile1074
Bacteria Under 5%ile139
Bacteria Under 1%ile07
Lab: BiomeSight
Rarely Seen 1%22
Rarely Seen 5%1214
Pathogens2922
Outside Range from JasonH44
Outside Range from Medivere1414
Outside Range from Metagenomics77
Outside Range from MyBioma55
Outside Range from Nirvana/CosmosId1919
Outside Range from XenoGene2121
Outside Lab Range (+/- 1.96SD)181
Outside Box-Plot-Whiskers7329
Outside Kaltoft-Moldrup8174
Condition Est. Over 99%ile00
Condition Est. Over 95%ile00
Condition Est. Over 90%ile11
Enzymes Over 99%ile10
Enzymes Over 95%ile32
Enzymes Over 90%ile2441
Enzymes Under 10%ile79240
Enzymes Under 5%ile26158
Enzymes Under 1%ile147
Compounds Over 99%ile02
Compounds Over 95%ile4113
Compounds Over 90%ile29453
Compounds Under 10%ile44163
Compounds Under 5%ile1861
Compounds Under 1%ile28

As often happens, there is a Yin/Yang with some indicators improving and other worst. My general impression is that this microbiome does better on Kefir.

Bacteria Specifics

I then went to compare specific bacteria shifts that had special interest or large shifts

BacteriaOn Kefir Percentile (Percentage)Stop Kefir Percentile (Percentage)
(genus) Bifidobacterium3572
(genus) Lactobacillusnone43
(genus) Blautia38 (6.5%)46 (7.2%)
(genus) Faecalibacterium34 (8.4%)62 (14.6%)
(genus) Lachnospira21 (0.6%)70 (3.5%)
(genus) Bacteroides66 (29.1%)88 (40.5%)
(genus) Phocaeicola79 (15%)93 (23%)

In terms of the literature, I could only find Bacteroides and Phocaeicola, which are both reported to increase (agrees). Different Kefirs will have different impact because each has different bacteria in it. “The kefir granules are a consortium of bacteria and yeasts embedded in a exopolysaccharide matrix. ” [2022]

See Milk kefir: composition, microbial cultures, biological activities, and related products [2015] for various lists of bacteria in different kefir tested.

List of Possible Bacteria in Kefir

The following list illustrates why I tend not to recommend Kefir — too many possible bacteria, some good and some bad. It’s probiotic roulette! If you buy commercial Kefir, have some fun — email the producer and ask which strains are in it, and the last full shotgun lab report verifying it.

  1. Acetobacter acetic
  2. Acetobacter fabarum
  3. Acetobacter lovaniensis
  4. Acetobacter orientalis
  5. Acetobacter rancens
  6. Acetobacter sp.
  7. Acetobacter syzygii
  8. Acinetobacter sp.
  9. Bacillus sp.
  10. Bacillus subtilis
  11. Bifidobacterium bifidum
  12. Bifidobacterium sp.
  13. Brettanomyces sp.
  14. Candida inconspicua
  15. Candida krusei
  16. Candida lambica
  17. Candida maris
  18. Candida sp.
  19. Cryptococcus sp.
  20. Dekkera anomala
  21. Dysgonomonas sp.
  22. Enterococcus durans
  23. Enterococcus faecalis
  24. Enterococcus sp.
  25. Escherichia coli
  26. Gluconobacter frateurii
  27. Gluconobacter japonicus
  28. Halococcus sp.
  29. Kazachastania khefir
  30. Kazachstania aerobia
  31. Kazachstania exigua
  32. Kazachstania unispora
  33. Kluyveromyces lactis
  34. Kluyveromyces marxianus
  35. Kluyveromyces marxianus var. lactis
  36. Lachancea meyersii
  37. Lactobacillus acidophilus
  38. Lactobacillus amylovorus
  39. Lactobacillus brevis
  40. Lactobacillus buchneri
  41. Lactobacillus casei
  42. Lactobacillus casei ssp. pseudoplantarum
  43. Lactobacillus crispatus
  44. Lactobacillus delbrueckii ssp. bulgaricus
  45. Lactobacillus helveticus
  46. Lactobacillus kefir
  47. Lactobacillus kefiranofaciens
  48. Lactobacillus kefiranofaciens ssp. kefiranofaciens
  49. Lactobacillus kefiranofaciens ssp. kefirgranum
  50. Lactobacillus kefiri
  51. Lactobacillus lactis
  52. Lactobacillus lactis ssp. lactis
  53. Lactobacillus parabuchneri
  54. Lactobacillus paracasei
  55. Lactobacillus parakefir
  56. Lactobacillus parakefiri
  57. Lactobacillus plantarum
  58. Lactobacillus satsumensis
  59. Lactobacillus sp.
  60. Lactobacillus uvarum
  61. Lactococcus cremoris
  62. Lactococcus lactis
  63. Lactococcus lactis ssp. cremoris
  64. Lactococcus lactis ssp. lactis
  65. Lactococcus lactis ssp. lactis biovar diacetylactis
  66. Lactococcus sp.
  67. Leuconostoc lactis
  68. Leuconostoc mesenteroides
  69. Leuconostoc paramesenteroides
  70. Leuconostoc pseudomesenteroides
  71. Leuconostoc sp.
  72. Naumovozyma sp.
  73. Pelomonas sp.
  74. Pichia guilliermondii
  75. Pichia kudriavzevii
  76. Pseudomonas sp.
  77. Saccharomyces cerevisiae
  78. Saccharomyces sp.
  79. Saccharomyces turicensis
  80. Saccharomyces unisporus
  81. Saccharomycodes sp.
  82. Shewanella sp.
  83. Streptococcus durans
  84. Streptococcus sp.
  85. Streptococcus thermophilus
  86. Weissella sp.
  87. Zygosaccharomyces sp.

Comments from Social Media

Border Walls in the Human

There are two border walls that can be important to health, we will used these terms:

  • increased intestinal permeability or IIP (often called Leaky Gut, but note: “Leaky gut syndrome is a hypothetical condition that’s not currently recognized as a medical diagnosis.”[src])
  • bloodbrain barrier permeability or BBBP

The first is an indicator of the availability of bacteria, fungi, chemicals, etc. to move from the intestines into the body/blood. The second is the ability of bacteria, fungi, chemicals, etc. to enter the brain. Both are important — the latter with neurological conditions (for example brain fog, autism, etc).

IIP – Increased Intestinal Permeability

This is usually associated with the Zonulin protein.

Zonulin is a protein modulator of intercellular tight junctions. It has been shown to induce a significant and reversible increase in gastroduodenal and small intestinal permeability and is involved in tolerance/immune response balance. The hybridization of wheat to dramatically increase gluten (gliadin) content and its overconsumption, multiple times a day, every day, in the typical diet, chronically disrupts this tolerance/immune response balance.

Michael T. Murray ND, John Nowicki ND, in Textbook of Natural Medicine (Fifth Edition), 2020

Zonulin is a member of the MASP (mannose‐binding lectin‐associated serine protease) family of proteins, and elevated serum zonulin levels have been reported in a number of neurological conditions such as multiple sclerosis 7 and Alzheimer’s disease. 8 

Zonulin and blood-brain barrier permeability are dissociated in humans [2022]

There is a massive number of studies, speculations, and theories on addressing this issue, especially theories on fixing leaky gut. One example:

BBBP – blood–brain barrier permeability

First, we need to be aware that they are different: Zonulin and blood-brain barrier permeability are dissociated in humans [2022]. For a general discussion, see A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity [2020]

Some studies that are of special interest:

When dealing with neurological issues when there is a choice of several different substances, I have looked up the molecular weight and advocated for the lower molecular weight choice. For illustration,

  • Acetylcysteine (N-acetylcysteine) has a weight of 163.19
  • Minocycline has a weight of 457.5
  • Azithromycin has a weight of 785
  • Amoxicillin has a weight of 365.4
  • Piracetam has a weight of 142 (this is a fast acting nootropic that clears brain fog in minutes for some people).
  • Resveratrol 228, Quercetin 302, Curcumin 368, Aspirin 180

It is an easy way to do quick evaluation— for example, I would expect Resveratrol to have a greater effect on brain function than Curcumin, with Aspirin having a still greater potential effect.

Bottom Line

The purpose of this post is frame questions that may be relevant to you — and not provide general answers.

Revisiting old data/post with latest tool set

A reader reminded me of A short ME/CFS/MCS remission with microbiome samples [2019], which used uBiome. The toolset has changed a lot since those days, so I thought it would be a good learning activity to look at the samples with the new tools.

The person had a short remission from ME/CFS after:

Analysis

The table below shows about the same number of bacteria identified but with an increase in the number of bacteria at extreme values. Condition Est. had a dramatic drop which would agree with the remission. We also see a dramatic drop in extreme Enzymes and Compounds.

In my humble opinion, it suggests that reducing extremes of enzymes and compounds is a desired objective goal.

CriteriaCurrent SampleOld Sample
Lab Read Quality9.18.1
Bacteria Reported By Lab327303
Bacteria Over 99%ile85
Bacteria Over 95%ile3822
Bacteria Over 90%ile7056
Bacteria Under 10%ile3821
Bacteria Under 5%ile2411
Bacteria Under 1%ile85
Lab: uBiome
Rarely Seen 1%31
Rarely Seen 5%264
Pathogens2624
Outside Range from JasonH77
Outside Range from Medivere1616
Outside Range from Metagenomics88
Outside Range from MyBioma1111
Outside Range from Nirvana/CosmosId1616
Outside Range from XenoGene3131
Outside Lab Range (+/- 1.96SD)1617
Outside Box-Plot-Whiskers12278
Outside Kaltoft-Moldrup156102
Condition Est. Over 99%ile00
Condition Est. Over 95%ile01
Condition Est. Over 90%ile111
Enzymes Over 99%ile00
Enzymes Over 95%ile5032
Enzymes Over 90%ile14894
Enzymes Under 10%ile80246
Enzymes Under 5%ile4550
Enzymes Under 1%ile61
Compounds Over 99%ile3182
Compounds Over 95%ile16465
Compounds Over 90%ile27535
Compounds Under 10%ile81319
Compounds Under 5%ile76237
Compounds Under 1%ile7270

Spot Checking Specific Bacteria Shifts

The more extreme bacteria shifts are shown below. The drop of Faecalibacterium levels was likely due to the drop of lactic acid produced by Lactobacillus [Metabolic Response of Faecalibacterium prausnitzii to Cell-Free Supernatants from Lactic Acid Bacteria 2020]. Given that the person has a ME/CFS diagnosis, my thoughts point to the massive reduction of Lactobacillus caused by Amoxicillin and Clavulanate resulting in a drop of lactic acid (see Lactic Acidosis in ME/CFS). While the bacteria producing lactic acid may be killed, it takes time for the system to clear it. Some sources cite a half life of 18 hours in the body[src]. The VSL#3 may be incidental or may have contributed to the remission ending.

BacteriaNewest Percentile(Percentage)Older Percentile(Percentage)
(genus) Alistipes31 (0.9%)89 (5.7%)
(genus) Anaerococcus97 (1.8%)62 (0.08%)
(genus) Bifidobacterium87 (3.6%)96 (7.3%)
(genus) Erysipelatoclostridium99 (3.9%)69 (0.7%)
(genus) Faecalibacterium19 (3.9%)51 (12.1%)
(genus) Finegoldia99 (3.5%)68 (0.1%)
(genus) Intestinibacter79 (0.4%)97 (2.4%)
(genus) Klebsiella91 (1.3%)none
(genus) Kluyvera89% (1.8%)none
(genus) Lactobacillus67 (0.01%)97 (3.5%)
(genus) Megasphaera96 (2.6%)76 (0.01%)
(genus) Parabacteroides95 (7.0%)81 (3.5%)
(genus) Streptococcus99 (7.3%)13 (0.003%)

Bottom Line

Short term remission causes are often difficult to identify the cause. In this patient, the evidence appears to be for a model of Amoxicillin and Clavulanate being effective against existing lactic acid producing species (i.e. Lactobacillus). It takes time for the lactic acid to clear the body. On the flip side, the lactobacillus would start regrowing and producing lactic acid (thus ending the remission).

A compounding factor is “Antibiotic Resistance of LACTOBACILLUS Strains [2019]”

For the subset of people with ME/CFS that improves on antibiotics and then regress; it is likely because the antibiotic suppress (but does not eliminate) lactic acid bacteria which then regrows…

Missing Vitamins, Minerals suggestions

Question:

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

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

Answer: No Reproduction

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

Long time ME/CFS

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

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

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

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

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

My first thryve was on January 13, 2020.

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

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

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

The request

First Look at the sample

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

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

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

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

Approach

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

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

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

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

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

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

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

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

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

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

Bottom Line

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

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

Postscript – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I cannot tell people what they should take or not take. I can inform people items that appears to have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting.

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

Blood Status influenced by the microbiome?

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

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

Xenogene: From Sweet Report to Bad Report

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

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

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

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

They Changed Their Report

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

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

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

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

Bottom line: I no longer recommend this lab

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

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

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

Citizen Science Action

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

Microbiome Activism Please!!

This applies not only to Xenogene but

and also these lacking NCBI taxon numbers

ME/CFS After Severe Stress

Backstory

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

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

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

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

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

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

~ Backstory ~

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

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

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

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

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

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

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

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

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

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

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

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

First Look at the sample

We have two Ombre samples on the account:

  • May 2,2022
  • Oct 18,2022

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

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

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

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

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

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

Approach

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

Early Sample

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

From Earlier Sample

Some illustrations from the literature of the suggestions

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

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

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

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

Example of how to do it

Latest Sample

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

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

Two Other versions of Suggestions

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

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

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

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

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

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

Note on the numbers on various lists

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

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

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

Postscript – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I cannot tell people what they should take or not take. I can inform people items that appears to have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting.

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

An update on results of prior analysis

This is a follow up of several prior posts

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

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

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

Why Follow Up Posts are important

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

Foreword – and Reminder

I am not a licensed medical professional and there are strict laws where I live about “appearing to practice medicine”.  I am safe when it is “academic models” and I keep to the language of science, especially statistics. I am not safe when the explanations have possible overtones of advising a patient instead of presenting data to be evaluated by a medical professional before implementing.

I cannot tell people what they should take or not take. I can inform people items that appears to have better odds of improving their microbiome as a results on numeric calculations. I am a trained experienced statistician with appropriate degrees and professional memberships. All suggestions should be reviewed by your medical professional before starting.

Comparisons between Samples

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

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

What do I see above?

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

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

Going Forward

KEGG Computed Probiotics

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

BBC Japan’s most polarising superfood?

Special Studies Numbers

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

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

Going forward

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

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

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

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

The probiotics suggested are

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

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

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

Fiber suggestions

The New Boy on the Block: Food Suggestions

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

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

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

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

Bottom Line

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

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

As well as agreement on avoiding

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

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

For most people, the best process stays the same:

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

Inaccurate Enterobacteriaceae/Escherichia/Shigella Reports

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

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

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

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

Some other recommended readings: