Back Story: 

Current Age: 25, male

Current Issues: chronic fatigue (not able to exercise or take walks longer than 10-15 min), strong brain fog & reduced cognitive abilities,

History: 

Covid-19 infection in June 2022 followed by intense fatigue, followed by 1.5M of recovery, followed by spontaneous, severe crash (Post-exercise malaise, fatigue, strong brain fog) and continuing since then
I tried a ketogenic diet for 6 months (and a carnivore 4:1 ketogenic diet for 1 month) to treat these issues but this actually seemed to make my symptoms worse. Tried a broad spectrum of high dose supplements, vitamins and minerals that did not help at all. Currently slow re-introduction of carbs into my diet again.

Analysis

I can only review the current state since I am microbiome data-bound in reviews. It was interesting that two popular approaches advocated by influencers made him worse. There is no universal solutions / cure. Solutions are specific to the individual.

My usual starting point for ME/CFS and post-COVID is the Percentages of Percentiles chart. It is not a match for the usual pattern seen for those conditions, but we see statistically significant abnormalities in the 10-19%ile range. I have not seen this pattern before.

Looking at Potential Medical Conditions Detected, only Mood Disorders stands out. This is consistent with his past history. For Dr. Jason Hawrelak Recommendations, he’s at the 75%ile with the main items of concern being high Bacteroides, Bilophila wadsworthia, and low Bifidobacterium, Roseburia, Akkermansia.

Looking at Special Studies, the top item is likely due to a hybrid ME/CFS with post-COVID:

Where Do We Go From Here?

I am going to build a consensus report from the 4 “Just Give Me Suggestions” to which we will add:

• Special Studies: COVID19 (Long Hauler)
• Potential Medical Conditions Detected: Mood Disorders

There are two ways of looking at suggestions (similar results but minor differences). Using the PDF Download or looking at the details.

In this case (these do not always appear), probiotics too.

Before moving onto the detail view, let us look at KEGG computed probiotics:

• #1 was Escherichia coli (which is symbioflor 2 above or Mutaflor). The items below are at 1/6th the estimated contribution.
• Latilactobacillus sakei subsp. sakei is also a positive in the list
• Lactococcus lactis and the other ones in Filmjolk (a Swedish drink) are positive. There are some retail variation availables else where, for example Siggi’s Filmjolk Drinkable Yogurt (other bacteria added) and some starters such as NW Ferments Filmjolk Yogurt Starter.
• Lacticaseibacillus casei, Lactobacillus gasseri are also positive

NOTE: Escherichia coli is a troublesome bacteria because it is poorly/not measured with the typical 16s technology.

In terms of detail view, the following are at the top:

• Cacao (540) see this 2012 post and 2017
• lactobacillus casei (probiotics)
• raffinose(sugar beet)
• lactobacillus gasseri (probiotics)

None of the antibiotics or prescription items are above 330; I am disinclined to consider them. During my own recovery, I found that I had a craving for peanut butter (some posts on peanuts: 2013, 2015). There is some evidence that it may improve the ability of the blood to delivery oxygen to the brain in some cases (which may help with cognitive issues). Peanuts do contain Resveratrol [2000] and the question arose below whether just resveratrol alone could be substituted?

Reviewing what he tried…

Ketogenic diet for 6 months… this actually seemed to make my symptoms worse.

I would expect that to make things worse — as shown above.

Tried a broad spectrum of high dose supplements, vitamins and minerals that did not help at all.

Remember that 50% of the highest value (540) is my usual demarcation line for suggestions (270). Interesting that not a single vitamin or mineral was even close! About half of them were negatives!

The response from what he tried pre microbiome-sample agrees with the predicted response.

What he should reduce or avoid

This leads us to the next item, items to avoid. They will definitely not sweeten up his life: minimum usage of sugar, saccharin, stevia – but raffinose is fine. Note that nuts are on this list — wait! How can this be? Peanuts is on the to take list. The answer is simple: misnaming. Peanuts are NOT nuts (they look like nuts) but a legume!

Questions and Answers

Q: the probiotics dosages stated on the page I was wondering: The page lists the CFUs as X*BCFUs (with the B meaning Billion I suppose?) tho the studies linked to the dosages used mostly dosages in the range of X*10^9 CFUs. Am I missing something? (Because e.g. for lactobacillus casei 48 x10^9 CFUs would seem a lot) 

• A: I do not know the number needed to insure effective change. The dosages are based on dosages used in Clinical studies and thus dosages that are inferred safe (and someone decided was needed — often the results of earlier studies where only a few responded). See 📏🍽️ Dosages for Supplements for links to the studies. There is a difference between maintenance dosages (keep the status quo) and therapeutic dosage (upset the microbiome’s apple cart).

Context for Next Questions

Cookbook Suggestions were created from a list of specific substances provided by a reader supporting Long COVID with some specific directions on how she wanted items evaluated. It is not the preferred list. The preferred methods are looking at the “Technical details” (in horrible complexities — with 1,774 entries for this sample) or using the PDF that filters to keep the number of items low but working off the same numbers.

Q: Cookbook suggestions:  Cookbook gave me a clear thumbs down for Bifidobacterium bifidum, and Lactobacillae Rhamnosus and plantarum, tho when I went into detail view or to the consensus suggestions they were ranked well along the other takes. Would you say therefore take or avoid is more recommendable (as I have two probiotics already at home that have these strains in them)

• A: As shown above, two are negative (thus avoid), the other one is low positive. (The values range from 539 down to -460). It is unlikely to have any significant impact.

Q: Peanut/ Resveratrol: In addition to eating peanuts, could I also use resveratrol extract to boost the process? 

• A: This raises the issue of humans wanting to simplify things, sometimes too far. Peanuts contains other things besides resveratrol. This could be it main mechanism of action — but other components may also be acting in isolation or combination. I checked the numbers, and would surmise that the other factors are significant contributors important here. Remember, we are working from very sparse data (despite having 1.9 million facts, we have 20,000 bacteria over 2000 modifiers. i.e. 1.9 million to 40 million combinations is only 5% (or less) hit rate).
  So, it may help — but not sufficiently to exclude peanuts (or that horrible American food: peanut butter!)

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 can compute items to take, those computations do not provide solid information on rotations, dosages, etc.

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. Some suggestions may be counterindicated for other medications you are taking and medical conditions.

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.

Autism is a variety of conditions caused by DNA mutations, environmental influences and a host of other factors. A significant contributor can be the microbiome. This impact can be further amplified because many children with autism are picky eaters shifting the microbiome further. What is discussed in this post applies to this child and not autistic children in general.

Back Story

A son with autism. He had COVID in April 2021. With autism, it can be challenging to identify long COVID symptoms from autism symptoms. “We have seen marginal  improvements in his receptive language and command following. His social skills and emotional understanding is poor . His diet has largely remained the same , vegetables and chicken , lamb, beef or fish and spices. He is verbal but not conversational, does not sleep well at night, does stimming throughout the day, his understanding is minimal He has very good energy levels and is playing till he sleeps on most days. He has very good memory and learn preferred topics quickly but is unable to focus on any task , he is unable to write or hold pencil for long . He cannot always reply to questions and has ecolalia[unsolicited repetition of utterances made by others] . ” 

Analysis

Lookin at Percentages of Percentiles, I see a different pattern than seen with ME/CFS and Long COVID — my most frequent analysis types. He has statistically (between 2 and 5%) significant abnormalities, but far less than people with ME/CFS and Long COVID.

Looking at Potential Medical Conditions Detected we see that ADHD and Mood Disorders patterns are there. Everything is reasonably in range for Dr. Jason Hawrelak Recommendations with two significantly out of range (too low) is Akkermansia (which is available as a probiotic) and Faecalibacterium prausnitzii is too high (27%). This pattern is seen across all of his samples.

Going over to our Citizen Science Special studies, the top three pattern matches are for:

• COVID19 (Long Hauler)
• Autism
• Brain Fog

These also are seen with an earlier sample from 2020.

Plan for Suggestions

Since this is a persistent state with reasonable continuity across samples, I am going to go the Uber-Consensus route. By this I mean we will do for Each Sample:

• “Just Give Me Suggestions” which executes 4 algorithms
• Citizen Science using Autism

Then we combine the suggestions from each sample into one, an uber suggestion consensus. The advantage of this approach is to minimize minor fluctuations of the microbiome over time. This means that we have 20 sets of suggestions combined.

I was disappointed with the results — nothing was consistently suggested. I experimented and found that the last two samples gave more consistent results. This implies that there has been significant changes in the microbiome over the last two years.

The top suggestions from the PDF are below

As a FYI, in terms of how many times things were suggested:

• blackcurrant – all 10
• low-fat diets – all 10
• red alga Laurencia tristicha – all 10
• lard – all 10
• Methionine – all 10
• fat – all 10
• glycyrrhizic acid (licorice) was 9 for and 1 against

I should talk a bit about the apparent contradiction with low-fat diets vs lard and fat. These come from the terms that clinical studies used. Low fat diet tends towards fish and poultry, lard is a pork product – I speculate that the type of fat may be significant.

On the flip side, we have these avoids. One item seems to be to suggest gluten free (despite wheat being a to-take):

As an experiment/learning activity — I looked at some of the suggested prescription items and checked if any are used for autism. We are matching these items impact on the microbiome and the shifts that this person has (autism as a diagnosis was not considered).

• cycloserine – D‐cycloserine for autism spectrum disorder [2019]
• Bumetanide – Bumetanide for autism: Open‐label trial in six children [2021]
• cefixime – Beta-Lactam Antibiotics as A Possible Novel Therapy for Managing Epilepsy and Autism, A Case Report and Review of Literature [2015]
• chlorpromazine hydrochloride – The Pharmacological Treatment of Autistic Spectrum Disorders [2014]

Since the non-prescription items above should cause similar shifts (and likely with less risk of side effects), it appears that the algorithms are making reasonable suggestions.

The process of checking suggestions derived exclusively from the microbiome against clinical studies for a condition is called cross-validation. When there is a high percentage of agreement, it implies that the mechanism may be via the microbiome and generating candidate substance from the microbiome may produce good results.

KEGG Based Suggestions

These use data from Kyoto Encyclopedia of Genes and Genomes to try to identify substances that the microbiome and the body may be short of which can be obtain via supplements or probiotics.

• Probiotics (in decreasing priority)
  • Escherichia coli – which can be Mutaflor (recommended above) or Symbioflor-2 (which is easier for people in the US to get).
  • There were several items that are counter-indicated from the suggestions – when there is disagreement, don’t gamble — ignore
  • Akkermansia muciniphila – low positive score but also identify as low on Dr. Jason Hawrelak Recommendations
• Supplements (again double checking across suggestions and keeping only that both agree with)
  • Biotin, Vitamin B7
  • Arginine
  • Glutamine
  • N-Acetyl Cysteine (NAC),

Questions

Q:  His gut according to the test is in good condition. I have heard in the past from one of his doctors that his Gut results were one of the best that he has seen in Autistic children, but we have not been able to make a considerable shift in his symptoms in the last few years.

• A: My working hypothesis is simple: symptoms are associated to microbiome shifts. He has bacteria shifts that are matches to autism drugs (see above); so I believe further improvement of the gut and behaviors are possible and probable. He may be good; I believe he can be better.

Q: Faecalibacterium prausnitzii is high in my son , I have read it works as anti-inflammatory , but on the contrary I have heard that children with ASD have an inflamed Brian ,I would have thought this would have worked in his favor.

• A: Excellent question! Faecalibacterium prausnitzii is anti-inflammatory for Crohn’s disease[2008], colitis [2013]. I was unable to find any clear literature on its effect on the brain. I did found some information that cause me to suspect that it does not impact the brain significantly.
  • “A 15kDa protein with anti-inflammatory properties is produced by F. prausnitzii, a commensal bacterium involved in CD pathogenesis. This protein is able to inhibit the NF-κB pathway in intestinal epithelial cells and to prevent colitis in an animal model.” [2017] – the size of this is very important.
  • “Most proteins in the plasma are not able to cross the blood—brain barrier because of their size and hydrophilicity.” [Basic Neurochemistry]
  • “does not have a barrier against molecules less than 1 kDa.. may form a barrier against molecules larger than 4 kDa” [2020]
• Bottom Line — it appears the chemical produced by Faecalibacterium prausnitzii may be too big to reach the brain.
• We also find the following reported, suggesting we want to reduce it to a normal range, you should independently research this
  • “Faecalibacterium predicted social deficit scores in children with ASD” [2018]
  • “Faecalibacterium prausnitzii … were also found to be highly correlated with Autism Treatment Evaluation Checklist (a measure of Autism severity )” 
  • On the flip side, it reduces abdominal pain and improved bowel movement in ASD [2018].
  • “Gut microbiome data revealed Akkermansia sp. and Faecalibacterium prausnitzii to be statistically lower in abundance in autistic children than their neurotypical peers with a five and two-fold decrease” [2021] — which may account for the gut issues.
    • “Compared with healthy controls, Faecalibacterium,..were more abundant in ASD patients” [2021]
    • Your son’s range is thus very atypical being many, many times higher than expected.
• I have caution here, Faecalibacterium and cognitive issues have inconsistent reports [2021, 2023 ], Faecalibacterium is implicated in cognitive issues[2018]. IMHO, encouraging it to the normal ranges may be the wisest course.

Q: “His results are over all satisfactory ,same as last year about – Gut wellness score – 89.52.  I have noticed that Clostridia is about 79.7 % could this be the reason, would appreciate your help.”

• A: Clostridia has been high in most samples, I drilled down into it’s main components
  • 2023-08-21: 80% of the microbiome, 88%ile — Oscillospiraceae 89%ile,  Faecalibacterium prausnitzii 96%ile
  • 2022-07-11: 86% of the microbiome, 92%ile — Oscillospiraceae 94%ile,  Faecalibacterium prausnitzii 95%ile
  • 2021-11-29: 80% of the microbiome, 88%ile — Oscillospiraceae 79%ile,  Faecalibacterium prausnitzii 79%ile
  • 2020-10-14: 83% of the microbiome, 98%ile —  Oscillospiraceae 100%ile, Faecalibacterium prausnitzii 100%ile

Searching for Faecalibacterium + autism on PubMed resulted in 29+ studies. There was nothing found for Oscillospiraceae + autism. Looking at the latest sample, only 10% of the organisms in Oscillospiraceae could be identified in the sample — no smoking gun for which genus. Doing a Metagenomic Shotgun Sequencing test would like provide more information (for example, Thorne) — but it is unlikely that will produce more actionable item — just give names.

Looking at what reduces Oscillospiraceae, we see Bumetanide, cycloserine, cefixime and chlorpromazine in that list (as well as many of the above suggestions).

Some visuals: Clostridia is not that extreme, but two of it’s children are.

This post started from reading “Dietary quality and the gut microbiome in early-stage Parkinson’s disease patients [2023]”. I posted on some Facebook groups “People often are obsessives with getting high Lactobacillus and Bifidobacterium. The “dividend” of this desire appears to be increased risk of Parkinson’s disease.“

The question arises, what other conditions are associated with high levels of both of these? Fortunately, this can be obtained from the Microbiome Prescription databases.

• Amyotrophic lateral sclerosis (ALS) Motor Neuron
• Autism
• Crohn’s Disease
• Depression
• Graves’ disease
• Inflammatory Bowel Disease
• Irritable Bowel Syndrome
• Juvenile idiopathic arthritis
• Liver Cirrhosis
• Long COVID
• Metabolic Syndrome
• Mood Disorders
• Multiple Sclerosis
• Obesity
• Parkinson’s Disease
• Psoriasis
• rheumatoid arthritis (RA),Spondyloarthritis (SpA)
• Schizophrenia
• Stress / posttraumatic stress disorder
• Type 2 Diabetes
• Ulcerative colitis

I also pulled the studies where the study specifically cited both are high. The above list were occasionally from taking data from two different studies.

• A prospective longitudinal study on the microbiota composition in amyotrophic lateral sclerosis [2020]
• The Impact of Microbiota on the Pathogenesis of Amyotrophic Lateral Sclerosis and the Possible Benefits of Polyphenols. An Overview [2021]
• The Role of Gut Microbiota in Gastrointestinal Symptoms of Children with ASD [2019]
• Increased proportions of Bifidobacterium and the Lactobacillus group and loss of butyrate-producing bacteria in inflammatory bowel disease [2014]
• Gut Microbiota in Anxiety and Depression: Unveiling the Relationships and Management Options [2023]
• Gut microbiome in chronic rheumatic and inflammatory bowel diseases: Similarities and differences [2019]
• IBS-associated phylogenetic unbalances of the intestinal microbiota are not reverted by probiotic supplementation [2012]
• Gut microbiota in pre-clinical rheumatoid arthritis: From pathogenesis to preventing progression [2023]
• A Metagenomic Meta-analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome [2019]
• Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study [2021]
• Composition, taxonomy and functional diversity of the oropharynx microbiome in individuals with schizophrenia and controls [2015]
• Changes of Colonic Bacterial Composition in Parkinson’s Disease and Other Neurodegenerative Diseases [2018]
• Meta-analysis of the Parkinson’s disease gut microbiome suggests alterations linked to intestinal inflammation [2021]
• Inflammatory microbes and genes as potential biomarkers of Parkinson’s disease [2022]
• Metagenomics of Parkinson’s disease implicates the gut microbiome in multiple disease mechanisms [2022]
• Altered fecal microbiota composition in all male aggressor-exposed rodent model simulating features of post-traumatic stress disorder [2018]
• Intestinal flora alterations in patients with ulcerative colitis and their association with inflammation [2021]
• The Gut Microbiome in Parkinson’s Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies [2022]

Bottom Line

A responsible medical professional would test a patient’s Lactobacillus and Bifidobacterium levels before suggesting probiotics to a patient. If your MD makes that recommendation without testing and you have any of the above conditions — it may be time to file a complaint with their supervisors or governing body citing the studies.

A reader forwarded me a study and some of it was interesting hints on this issue.

In vitro experimental results show a potent inhibitory effect (greater than 90%) of chloroquine, a historical antimalarial active ingredient, and clavulanic acid, a β-lactam antibiotic widely used in combination with amoxicillin [80]. A significant inhibition of the enzymatic activity has also been observed with the antihypertensive drug verapamil and the histamine H2 receptor antagonist cimetidine, although the clinical use of the latter is currently anecdotal

Histamine Intolerance: The Current State of the Art [2020]

My idea is to examine which bacteria these items impact and see if there is a pattern.

The full list is below

Active Ingredient	Indication
Chloroquine	Antimalarial
Clavulanic acid	Antibiotic
Colistimethate	Antibiotic
Cefuroxime	Antibiotic
Verapamil	Antihypertensive
Clonidine	Antihypertensive
Dihydralazine	Antihypertensive
Pentamidine	Antiprotozoal
Isoniazid	Antituberculous
Metamizole	Analgesic
Diclofenac	Analgesic and anti-inflammatory
Acetylcysteine	Mucoactive
Amitriptyline	Antidepressant
Metoclopramide	Antiemetic
Suxamethonium	Muscle relaxant
Cimetidine	Antihistamine (H2 antagonist)
Prometazina	Antihistamine (H1 antagonist)
Ascorbic acid	Vitamin C
Thiamine	Vitamin B1

We have 14 items that we have data on.

At the family level, the following at the commonly impacted — all were decreased.

• Bacteroidaceae – 14
• Desulfovibrionaceae -14
• Enterobacteriaceae -13
• Clostridiaceae -13
• Peptostreptococcaceae -13

At the genus level we have these all at 14 matches and decreasing

• Bacteroides
• Bilophila
• Lawsonia
• Desulfovibrio
• Anaerorhabdus
• Desulfocurvus
• Desulfobaculum
• Halodesulfovibrio
• Mediterranea
• Pseudodesulfovibrio
• Desulfohalovibrio
• Desulfocurvibacter

There are no clear smoking guns. When we include Special Study: Histamine or Mast Cell Issues we see that histamine issues are associated with lower levels of many bacteria (where as the above are those implicated in higher levels). We also looked at histamines in Exploration: Salicylate Sensitivity And the Microbiome, where we see under detection usually being the characteristic for histamine issues (except for Rothia mucilaginosa.

Doing cross checking, we find that the following are not reported impacted by the above AND are low in the other studies:

• Methanobacteriaceae (family) – none
• Heliobacteriaceae (family) – none
• Anaeroplasmataceae (family) – none
• Desulfocella (genus) – none
• Spirosomaceae (family) – none
• Rhodocyclaceae (family) – none
• Cytophagaceae (family) – none
• Ezakiella (genus) – none
• Halobacteroidaceae (family) – none
• Burkholderiaceae – only 1 impacts
• Limosilactobacillus – only 10 impacts

All of the “none” are most likely due to this family or genus not be measured in the studies used. This leaves one bacteria of interest: Burkholderiaceae.

Bottom Line

We have no clear pattern. The drugs at the top likely makes room for bacteria that are low in frequency and amount to grow. Our attempt to find the bacteria ignored by the drugs above AND which are seen at low levels only turned up one candidate with a manual review: Burkholderiaceae.

Writing code to drill deeper may find more — stay tune.

I am newly ill from ME/CFS (4-5 months) and wonder if my results look like a “typical ME/CFS” for you, or Long Covid for that matter.  I am a bit confused and some of the recommendations are contradictory.

From Reader. He used Biomesight.com (serves the world, discount code “Micro”)

This will be an interesting analysis — the microbiome evolves over time, so a 20 year ME/CFS and a few months of ME/CFS will have differences. I know of no clinical studies looking at “fresh ME/CFS”. There are studies for “fresh Long COVID”.

Percentages of Percentiles

This tend to have a regular pattern for ME/CFS and Long COVID for most people. Over representation of bacteria in the 0-9% percentile range. This matches his pattern. A healthy person would have all of the bars around 10% – they are not.

Going to the Potential Medical Conditions Detected, there was nothing significant. Prevotella copri is 2% (78%ile) which is borderline for mold issues — it would be good to do inspect the home for that risk. Dr. Jason Hawrelak Recommendations comes in at 99.7%ile with high Methanobrevibacter and low Bifidobacterium being the most severe shifts. Anti inflammatory Bacteria Score is 63.1%ile which is a bit better than most people. So, many medical professionals would tell the patient that I cannot see anything wrong.

Special Studies

Special studies are statistical studies that uses samples uploaded and look at the self-reported symptoms. The analysis is done individually for each lab (needed because of differences in how labs process samples). In this case… we see that COVID Long Hauler is by far the strongest match, almost double the next one.

I did the usual Just Give Me Suggestions and then did the Long Hauler suggestions . This gave five (5) packages of suggestions. I then looked at the antibiotics suggestions, focused on those used with ME/CFS. The top ones are:

• METRONIDAZOLE (ANTIBIOTIC)
• AZITHROMYCIN,(ANTIBIOTIC)S
• CHLOROQUINE DIPHOSPHATE
• DAPSONE (ANTIBIOTIC)

If you have a cooperative MD, I would suggest following the protocol of the Belgium MD, Cecile Jadin: Dr. Jadin’s Current Protocol for ME/CFS.

The list of suggestions to take is actually bigger than usual.

• REMEMBER: There is no need to take all of them, just take what works for you (i.e. no adverse effect and acceptable cost).
• Probiotics should be rotated (change to a different one) every 7 to 14 days. Probiotics often work by producing natural antibiotics. Continuous taking of the same probiotics may result in it not working because of “natural antibiotic resistance”.
• The colors have no meaning except as indicators for category. For example, green is probiotics
• Dosages are those that have been used in clinical studies (for other conditions), and thus deemed safe dosages. Often I have see people taking < 1% of these dosages and wondering why nothing happens.

For example, it you are lactose intolerance, then ignore the lactose suggestion. If not, regular cups of good Belgium Cacao would be a good prescription!

The safe retail probiotics were calculated to be

• symbiopharm/ symbioflo2 – an E.Coli probiotic from Germany
• Filmjölk (SE) / Filmjölk – a Swedish milk drink
• enterogermina – Bacillus Clausii
• SunWavePharma / Spor Sun – Bacillus Clausii

Why are these lists not the same? The latter list are ones that will not shift a single one of the bacteria we are focused on in the wrong direction: NOT A SINGLE BACTERIA. This is an extremely safe conservative suggestion. The top list with probiotics in green often contain probiotics that shifts 30 bacteria in the right direction and 3 in the wrong direction. The odds are that they are very likely to help.

We have a third list of probiotics (to make probiotic suggestions even more confusing), the KEGG suggestions. This looks at what enzymes your microbiome are low in, then sees which probiotics can provide those enzymes. Our goal is to reduce enzymes starvation; this cascades in metabolites — chemicals that the body uses — starvation. The key items from this list are:

• Escherichia coli (symbioflor-2 above or Mutaflor)
• Bacillus subtilis subsp. natto (1/3 of contribution of E.Coli probiotics)
• Bacillus subtilis (1/3 of contribution of E.Coli probiotics)
• Lactobacillus plantarum subsp. plantarum (1/4 of contribution of E.Coli probiotics)

If you have significant brain fog, I would be careful with taking lactobacillus probiotics. Some retail species can increase brain fog.

The Avoids

Frequently “good suggestions for general health” are bad for some conditions. The avoid list of things to avoid is short

Some quick translation: no iron supplements (ferric citrate), beta-glucans usually means no oats, barley or Reishi mushrooms. The names are those used in clinical studies — so they tend to be “unresolved” often in common speech.

Suggested Cycles

After implementing the above suggestions for 6 weeks, do another test and see what has changed.

Questions and Answers

Q: Is it best to take the antibiotics + the protocol you suggested ? Or is it one or the other?

• A: My own choice would be to do both at the same time. If you follow Jadin’s approach, then
  • First week of antibiotics per month — no probiotics at the same time
  • Second week do some of the probiotics (I am inclined towards the E.Coli probiotics but that is based on my personal experience — your mileage may vary)
• Rotate the other supplements over the weeks. I would suggest 10 days and then change to a different set.

Q: And lastly, in the « Avoids », the « vegetarians » suggestion is a little confusing to me. What does it mean?

• Vegetarians mean no animal or fish is being consumed. So, have fish — but some animal proteins are to be reduced: no pork, moderate beef. Duck, chicken and rabbit are fine.

Q: The suggested dosage in the suggestions seems very high. 30g of Vitamin C per day??? Is this correct ?

• The actual dosage should be discussed with your medical professional. The dosages are the highest that have been done in clinical studies and thus assumed to be safe dosages. We have no data on what the threshold for an effective dosage should be. I have seen a few studies where 1000 mg of a substance has minor/no effect while 1100 mg has twice the impact and 1200 mg has four times the effect. For many substances there seem to be a threshold that triggers changes.
  • Usually start at 1/8 of the dosage and double it every second day until there is a response. If very good keep at that dosage. If bad, cut the dosage in half and try a few more days. Give the body time to adapt.

My comment about mold caused him to check his environment carefully…. what he found out of sight!

Mold and ME/CFS Relationship

“Urine specimens from 104 of 112 patients (93%) were positive for at least one mycotoxin” from Detection of Mycotoxins in Patients with Chronic Fatigue Syndrome [2013]

“Environmental factors – exposure to mold or toxins has been suspected as a trigger for ME/CFS. However, associations of specific environmental factors with ME/CFS have not been established.” [CDC]

Prevalence of Aspergillus-Derived Mycotoxins (Ochratoxin, Aflatoxin, and Gliotoxin) and Their Distribution in the Urinalysis of ME/CFS Patients [2022]

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 can compute items to take, those computations do not provide solid information on rotations, dosages, etc.

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. Some suggestions may be counterindicated for other medications you are taking and medical conditions.

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.

This is from a reader that I have been corresponding with since 2017 and known from online groups for decades..

Okay, you don’t want the full saga 😀 (joking ) and so I’ll write the first current impressions of a ME/CFS patient since 1998. I am someone who has tried everything; really everything.
First of all, as I had already told you in chat, I use as a criterion of improvement in the disease the increase in cardiovascular tone, which actually happened for a short time as long as I kept a diet that was not exactly ironclad, but very difficult for me: it involved cutting out all refined sugars.

For those interested, I talked about it here : https://www.fable.it/fluorochinoloni-hrv-dieta-e-me-cfs/ (in Italian — use Google translate) . For the first seven days of the diet nothing changed, nothing! After these 7 days suddenly, keeping to this diet , cardiovascular tone started to increase until … well … I kept the rest of the diet but reintroduced sugars (but not alcohol). Then improvement stopped (but maintained existing improvements).

From Reader

Recent significant events are:

• fluoroquinolones toxicity in 2020
• supplements of akkermansia muciniphila one month before last sample  (see below for his experience)

Ancient Test Results

A test result from 23 August 2016 is below. The test is only of a few bacteria without any ranges of normal valid. We will compare the few items reported with the latest Biomesight test. There was little change over 7 years.

Any persistent Fluoroquinolones artifacts?

I did a behind the UI comparison of what Fluoroquinolones changed with his sample. Although it has been 3 years, I am curious. No impact would have 50-50 agreement. We have 64 bacteria showing the effect that that Fluoroquinolones would cause, and 43 showing the opposite effect. This results in a P-Value of 0.0423 from chi-square. A P-value below 0.05 is deemed statistically significant in medical studies. So, this is evidence that the impact of Fluoroquinolones is still there after 3 years.

This is an interesting observation — picking the wrong antibiotic may have effects that persists for years.

Comparing to Ancient Test Shown Above

Each lab uses their own methodologies to measurements (See The taxonomy nightmare before Christmas… for why and Comparing Microbiomes from Three Different Providers for actual example). So we cannot determine if the levels have gone up or down.

• Bacteroides caccae is at 15%ile, still low
• Barnesiellaceae is 0%ile, still low
• Parabacteroides distasonis is 12%ile, still low
• Prevotellaceae is 97%ile, still high
• Prevotella is 97%ile, still high
• Prevotella copri is 95%ile, still high
• Prevotella stercorea is 96%ile, still high
• Anaerostipes is 0%ile, still low
• Catenibacterium is 93%ile, still high
• Clostridium is 26%ile, still low
•  Lachnospiraceae is 2%ile, was high
•  Megasphaera is 95%ile, still high
• Mitsuokella was not reported, was high

The microbiome was been relatively stable over 7 years. In fact, the Biomesight test clarify how extreme the values are (which is not clear from the earlier report).

Where do we go from here?

The Percentage of Percentiles pattern shown below is a match for that seen with many ME/CFS or Long COVID microbiome.

Nerdy Explanation: Using percentiles, the data is transformed to an uniform distribution. An unbias sample (a.k.a. normal or healthy), would have the same number in each 10%ile range. We do not. We have the typical spike in the 0-9%ile range (i.e. too many species and genus that have token representation).

The most important/concerning bacteria identified was Prevotella copri. This bacteria made up 43% of the microbiome!!!! This bacteria is often associated with mycotoxin being present in the environment [2020]. This usually means examining the living space for mold and fungi, as well as avoiding foods likely to have mold (see WHO for more information). His response to this comment was:

Yes, I live in a north-oriented flat where never there is sun on walls. Only in a bedroom not used anymore as bedroom I have visible mold (picture attached). I have tried treating with chlorine bleach. In February 2023, I called a painter. He treated with anti mold solution and thermal painting (which can ben dangerous. I would never lived in that bedroom till the smell went away.
And yes, sun recharge me and I don’t know if it also affects mycotoxins. However in my block / area where I live, we never have less than 60% humidity, but in summer usually we have 70-75% so… humidity is a concern.

From Reader

There are many sites providing suggestions on this issue, a few are: [Aircare Hawaii] and this

Is mold related to humidity?
European and Italian homes are typically built with reinforced concrete frames and brick walls.
Walls and ceiling surfaces are finished with mortar/plaster and water base paint. As water base
paint is not waterproof, plaster finishing tends to absorb and retain humidity. These areas can
become damp or wet as a result of a water leak or condensation of vapors produced by appliances
and normal household activities.

From https://www.aviano.af.mil/

The use of a waterproof paint after cleaning (and running a dehumidifier) in the bedroom is one possible approach. Reader responded (to his delight) that water proof paint was used!

This plus other shifts, matches to a host of conditions shown below. Many are co-morbid with ME/CFS.

The Computed Probiotics from KEGG Enzymes had some very high numbers (over 600!). High numbers mean that there count of many enzymes is very low. Some of these are available in probiotics, with the top feasible suggestions being:

• Escherichia coli
• Brevibacillus brevis
• Bacillus subtilis
• Bacillus licheniformis
• Bacillus subtilis subsp. natto
• Clostridium butyricum
  

Two retail probiotics for the Bacillus above are: Energybalance / ColoBiotica 28 Colon Support and microbiome labs/ megasporebiotic. The person is in Europe, so the two E.Coli probiotics: Symbioflor-2 and Mutaflor are available. For others, see Probiotic Mixtures.

I will defer the rest of the suggestions to the PDF, attached below. It is interesting to note that akkermansia muciniphila probiotics is well recommended (see experience below).

In this case, we have good positive reader experience happening before the suggestion was made! It should encourage the reader to trust the other suggestions (after all, “one suggestion worked before he got it!” 🙂 )

I also looked at the MD version which suggested a few antibiotics:

• oxytetracycline dihydrate (antibiotic) – a broad-spectrum tetracycline antibiotic
• thiamphenicol (antibiotic)
• ß-lactam (antibiotic)s (33% of p.copri resistant [2022])

None of these are typically used for ME/CFS (but other tetracyclines are). We have one big target: P.Copri. I am hoping that you have a cooperative MD. I checked around for information on antibiotics that often have little effect on P.Copri, these studies have extensive lists.

• Antibiotic resistance in Prevotella species isolated from patients with cystic fibrosis [2013] – you want runs with R being a zero (0) in Table 1
  • I am inclined to metronidazole, which is often used in treating ME/CFS (also in this 2010 study), and 98% effectiveness reported in this 2019 study.
    

Akkermansia Muciniphila Experience

Another thing Ken, is the sensational discovery this year of Akkermnasia Probiotics (in my case from Metagenics). In my first two days I went from going to the bathroom once a day to going three four times. How many times have we read that a normal bowel transit involves 1 evacuation a day to one every 2-3 days ? No ! The ideal transit is to go to the bathroom about half an hour after eating ! Well, this happened to me while supplementing Akkermansia once a day. And it is only one strain !!! Not only that ! I felt less “Fight or Flight” but more serene, even when I woke up from my night sleep. Even with scabs on my eyes that who knows how many years I haven’t found (how many of us have perpetually dry eyes ?). I stopped the supplementation after a month and am now resuming it.

Why am I writing you this Ken ? To waste your time !!! No, I am writing this to you because I had first read about this Akkermansia three years ago on the label of an Austrian product, Omni Logic Plus, which contains a lot of good stuff (FOS, GOS , etc.) to feed this specific bacteria, Akkermansia . Three years of supplementation every day has not improved anything.
After just a few days of Akkermansia , that is, the strain that that Omni Logic Plus was supposed to feed, did the miracle ! What do I mean by all this ? That , my thought is that rather than acting on the food, if they are available as supplements, little bacterial strains should be introduced, for a far better effect.

From Reader

Questions:

Q: When the “nutrients” of the supernumerary bacteria present they grow. If you cut off their nutrients, the effect on microbiota diversity is extremely “reactive” !!! Whether this happened when I removed the sugars ?? Do you agree with my reasoning ?

• A: Yes — consider a human population that is well fed (obese even). If you suddenly impose strict rationing on them, their behavior changes greatly (often with criminal actions).

Q: Is it more effective to remove the food that feeds the overrepresented bacteria and simultaneously supplement the underrepresented strains not so much with diet and food, but with probiotics ?
An example of my personal case ? When in the report generated by your site I see among the recommendations clostridium butyricum , which I never tried in my life.

• A: The algorithms effectively does that — identify the material that inhibits the overrepresented which do not impact the underrepresented. Also the reverse, feed the the underrepresented without feeding the overrepresented. You can try to calculate these manually — but its a massive amount of reading and searching. Microbiome Prescription uses some 1.8 million facts pulled from almost 12,000 studies.

Q: Who knows if it can give me the same benefits as Akkermansia? After years where weeks on end , I have tried various products. Like everyone else, I have been spending hundreds of Euros. For example:

• probactiol duo ( billions of Saccharomyces boulardii)
• 8.5 billion of a probiotic blend – HOWARU blend (Lactobacillus acidophilus NCFM®, Bifidobacterium lactis Bi-07®, Lactobacillus paracasei Lpc37™, Bifidobacterium lactis Bi-04™)

• A: The purpose of Microbiome Prescription is to compute the most likely ones based on your microbiome and what studies reports the effects of various probiotics are. This means greatly increased odds of positive effects! Much better (and cheaper in the long run) than trying things suggested by influencers or which worked for someone with a very different microbiome.

Your list is very short — 50% is what you recently discovered works!!

For probiotics, do one at a time for 10 days then rotate to another. Why? Their effect is often due to natural antibiotics that they produce. Keeping on them continuously allows “natural antibiotic resistance” to develop.

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 can compute items to take, those computations do not provide solid information on rotations, dosages, etc.

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. Some suggestions may be counterindicated for other medications you are taking and medical conditions.

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.

I was messaged

Ken, I read so much of your stuff, I have ZME 39 years. My granddaughter has POTS and now she was diagnosed with SIBO and fructose Intolerance. Could you point us to a diet for SIBO; She has not been given one nor can find it. I thought of you right away, Please help. Have a great weekend, holiday.

What has been actually studied

First, the reality of SIBO diagnosis. IMHO, it tends to be a little “hit and miss“.

Although abdominal bloating, gas, distension, and diarrhea are common symptoms, they do not predict positive diagnosis. Predisposing factors include proton-pump inhibitors, opioids, gastric bypass, colectomy, and dysmotility. Small bowel aspirate/culture with growth of 10-10 cfu/mL is generally accepted as the “best diagnostic method,” but it is invasive. Glucose or lactulose breath testing is noninvasive but an indirect method that requires further standardization and validation for SIBO. Treatment, usually with antibiotics, aims to provide symptom relief through eradication of bacteria in the small intestine. Limited numbers of controlled studies have shown systemic antibiotics (norfloxacin and metronidazole) to be efficacious. However, 15 studies have shown rifaximin, a nonsystemic antibiotic, to be effective against SIBO and well tolerated. Through improved awareness and scientific rigor, the SIBO landscape is poised for transformation.

Small Intestinal Bacterial Overgrowth: Clinical Features and Therapeutic Management [2010]

• “Because there is currently no gold standard for diagnosing SIBO, its prevalence and role in the pathogenesis of other diseases remain uncertain; as does optimal treatment of patients with relapsing symptoms.” Small Intestinal Bacterial Overgrowth: Nutritional Implications, Diagnosis, and Management[2017]

There are dozen of diets pushed by influencers for diverse reasons. I tend to be a “show me the clinical studies or reviews” type. What do we find is…

This narrative review suggested that there is a favorable association with monoprobiotics, fiber supplementation and mindful eating, and negative effects associated with low-FODMAP diets on the gut microbiome, especially in IBS patients. Applying these recommendations to the treatment of SIBO was inconclusive due to a lack of research including SIBO patients in the studies. 

Efficacy of an Irritable Bowel Syndrome Diet in the Treatment of Small Intestinal Bacterial Overgrowth: A Narrative Review [2022]

Our findings suggest preliminary evidence for a role of alternative therapies in the treatment of SIBO. However, robust clinical trials are generally lacking. Existing studies tend to be small and lack standardized formulations of treatment. Breath testing protocols and clinical symptom measurement greatly varied between studies. Large-scale, randomized, placebo-controlled trials are needed to further evaluate the best way to utilize alternative therapies in the treatment of SIBO.

Alternative Treatment Approaches to Small Intestinal Bacterial Overgrowth: A Systematic Review [2021]

Where do we go from here?

My inclination is to encourage a suitable microbiome test (OmbreLabs, Thorne or Biomesight.com [discount code: Micro] and use the Microbiome Prescription site. There is an apriori set of suggestions based on the bacteria reported from studies. It is interesting to note that rifampicin antibiotic is suggested which is closely related to rifaximin which is cited in the study above, suggesting that working from the microbiome data is a reasonable approach. Other diet related items computed are:

• aspartame(sweetner)
• bifidobacterium adolescentis,(probiotics) 12BCFU/day
• carob
• catecholamines(polyphenol)
• e.coli probiotics (Mutaflor, Symbioflor-2)
• dairy / lactose /lactulose
• d-ribose 10gram/day
• fat in diet
• fluorine (i.e. in toothpaste!)
• fruit/legume fibre
• grape polyphenols
• green-lipped mussel
• iron 400mg/day
• ku ding cha tea
• mannooligosaccharide(prebiotic) 8gram/day
• Miso
• navy bean
• non-starch polysaccharides
• oligosaccharides(prebiotic)
• proton-pump inhibitors(prescription) 60mg/day
• Pulses
• raffinose(sugar beet)
• red alga Laurencia tristicha
• red wine 250ml/day
• rice bran
• sodium butyrate
• Sriracha sauce
• ß-glucan 500mg/day, converting to foods:
  • Mushrooms, especially shiitake, maitake, reishi, shimeji and oyster varieties
  • Date fruit, a sweet and fiber-rich fruit native to the Middle East
  • Oats, a cereal grain that can help lower cholesterol levels
  • Barley, one of the highest-fiber grains
  • Seaweed, a marine algae that contains various nutrients and antioxidants
  • Rye bread, a type of bread made from rye flour [Sources of Beta-Glucan (weekand.com)]

Do just the items that you tolerate (physically, philosophically), there is not a need to do all.

Items to AVOID include:

• cinnamon (oil.spice)
• foeniculumvulgare,fennel
• lactobacillus plantarum(probiotics)
• oregano(origanum vulgare, oil) |
• syzygiumaromaticum(clove)
• thyme(thymol, thyme oil)
• triphala

I would extend it to all lactobacillus probiotics because there are hostile to E.Coli probiotics.

Bottom Line

Working from an individual microbiome is the best way to proceed (IMHO). There are massive issues with both being sure of the SIBO diagnosis being correct AND no clinical evidence (except for antibiotics use) of any specific diet being useful.

Over the last week I have been working on Exploration: Salicylate Sensitivity And the Microbiome with some success. I rolled one analysis feature into a new page that may give scents as to causes.

The basis is that we look for bacteria that are seen more or less often than expected. Bacteria distribution is not a bell curve/normal distribution which makes the use of averages very suspect. Checking against frequency side-steps this answer.

Direct Link: MicrobiomePrescription : Abnormal Frequency of Bacteria for Symptoms

You can select the lab source and up to two symptoms.

There may be no data (if there is not sufficient data) for some single symptoms or symptom combinations.

Why are the Bacteria Names Different?

This is because there are no standardization of reading 16s Data Files (FastQ). See The taxonomy nightmare before Christmas…

Explore and share any interesting discoveries….

You can even see some shifts with age!

If there is sufficient data to hazard suggestions a red button will appear at the bottom:

This report indicate the experimental nature of the report and the lack of data on many bacteria.

This is an update on this earlier post. New Reports for Medical Professionals
There has been two additions:

• Retail Probiotics are listed (if there are any!)
• Uber Consensus now has the ability to generate a PDF
  • This is particularly for people that used Ombre and then had the FastQ files processed by Biomesight.

Probiotics Example

These are only the completely safe ones that will have some benefits. There may be none reported.

Uber Consensus

When you view the consensus, you can then get the report

One word of warning: the bacteria list may be massive — especially when different labs are involved.

For the sample below — it is FIVE pages.

I would be interested to see how the three separate consensus suggestions compare (i.e. not doing the uber consensus). Do the top takes & avoids match across the different labs, or are they different? Because if they are different then the algorithm is not robust to changes in lab.

Request from a reader.

This is a part of this series of post:

• Comparing Microbiomes from Three Different Providers – Part 1.
• Ombre Suggestions Analysis – Failing Grade – 2A
• Biomesight Suggestions Analysis – Good Results – 2B
• Thorne Suggestions Analysis – INCOMPLETE / FAILED – 2C
• Microbiome Prescription Uber-Consensus Analysis – Excellent – 2D

Using the same data, the process that I will use is where items suggested in both are the same (i.e. take or avoid) or different recommendations. In pseudo sql:

Select Percent(A.Take=B.Take) from Suggestions1 A Join Suggestions2 B on A.substance=B.substance

The results actually surprised me!

Lab Comparison	Items	Agreement	Avg Difference
Ombre vs Biomesight	1705	100%	52
Ombre vs Thorne	1706	100%	100
Biomesight vs Thorne	1694	100%	54

My expectation was somewhere between 80-90%, the same range that I got doing cross validation. The Priority and weight are different, but the take or avoid decision are the same. The difference between these pseudo values was also calculated and added to the table above. Magic Soy on Ombre may be 430, on Thorne 330, on Biomesight 530.

Conclusion, the algorithm is more robust than I expected!

Caveat: This was done using “Just give me suggestions” collection of algorithm on each lab’s data. Disagreements are definitely expected when bacteria selection are “over-focused” and not including the holistic picture of the microbiome.