The problem with “official” ranges from labs

Ranges are created by labs to be able to give answers to people asking for them. The key word is created. They may have no actually be healthy ranges for your age, gender, diet style etc. Say again! Not actually healthy ranges for you.

At the highest levels of the bacteria are phylums:  (Firmicutes and Bacteroidetes). Almost every bacteria belongs to one of these two phylums. Almost every person in the US would be unhealthy by Indian Standards — well outside of the typical ranges. And almost every person in the India would be unhealthy by US Standards — well outside of the typical ranges. If you are of Indian descent living in the U.S. and eating a mixture of Indian and Western foods… any ideas of what you healthy range should be?

The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? [2020]

The classic approach in most labs for other tests (like Vitamin D, iron, etc) is to get a collection of apparently healthy individuals from physically around where the lab is and the assume that the data will be a bell curve/normal distribution. The people are typically self-declared to be healthy – for Americans, this will usually be high in people that have a high body-mass index [BI] (i.e. overweight). We know that a high BI causes changes in the microbiome…. From that data, compute the range — see typical instructions to labs here:  Standard Lab Ranges (+/- 2 Standard Deviations). This assumption is never validated statistically on the data – lack of appropriate skills in the lab is a common cause. If you attempt to validate against almost any bacteria in the microbiome — it will fail, often extremely fail.

Research scientists knows that this is making a huge assumption and will often in their research papers use a method called Box Plot Whisker. It is definitely better but typically require more samples to establish the ranges. A lab manager will opt not to do it when he may only need to do 30 samples to get the Standard Lab Ranges, and may need 150 samples to get a good Box Plot Whisker. Why should he want to increase costs when he can go cheap and claim that he is following standard processes.

Wait! There is More!

Suppose that you get 200 “healthy samples” — we can get the ranges using Box Plot Whisker and that’s it! We now know what healthy ranges are then!!!

WRONG!!! VERY WRONG!!! The National Institute of Standards and Technology (the same people who define how long a foot is, or how many lumens a light bulb has) has made if very clear!!!!

If we have 200 samples, we will likely have 97 different ranges!!

From https://cfsremission.com/2019/12/22/the-taxonomy-nightmare-before-christmas/

Some of the ranges from different ways will be in significant contrast with each. To illustrate this, let us look at samples uploaded from OmbreLabs and Biomesight — they both use the same physical lab that has the same equipment — the difference is the software (“the ways”) that they use on the identically same data file!!!! We are NOT talking about two samples from the same stool; we are talking about one sample only

LabBacteria/Taxa Types
BiomeSight 4193
OmbreLabs6549
uBiome2324
All consumes the same FASTQ raw data — the difference is the software they use

Looking at frequency of detection, we have some good matches at the genus level

Tax_NameBiomeSight
% Detected
OmbreLabs
% Detected
BiomeSight
Average %
OmbreLabs
Average %
Vibrio3.8883.9070.0030.003
Nitrobacter0.2990.3190.0020.002
Prochlorococcus0.1790.1590.0030.003
Ruegeria0.1790.1590.0010.004

And some bad ones!

Tax_NameBiomeSight
% Detected
OmbreLabs
% Detected
BiomeSight
Average %
OmbreLabs
Average %
Rhodothermus90.3711.9140.2750.039
Escherichia80.7425.1830.5360.058
Pedobacter97.96724.0830.9360.014
Alkaliphilus97.18928.6280.3480.011


Whose right? Both are right and both are wrong — there is no standard!!!! Right assumes a shared upon norm or consensus by people concerned.

What is my personal solution?

I am by academics and industrial experience, a statistician, operational research and Artificial Intelligence Software Engineer. The way to get the most probable solution from a difference of opinions, is to build a consensus model — take every ones suggestions and combined them!

At present I have good number of opinions that can be used, and if I get more expert opinions (and permission to use them) I will gladly add them.

I would love to see all of the labs make public the data they used to construct their ranges. Open data. I have discussed that with some of them and they deem it to be “proprietary” data. It is, in that the disclosure may reveal their mistakes and expose their ranges as questionable. Every one’s ranges are questionable (IMHO).

There is no right answer. There is no trustworthy range. A consensus answer is likely a good answer, the best that is available at the moment.

Another ME/CFS person has gone to Firmicutes!

Report Back

As an update, I’m nearly 5 weeks in and am beginning to feel better.  My energy levels are perhaps the best they’ve been in the last 5 years.  I’ve still got a very long way to go but the results thus far are promising!

I’m taking 5-7 foods/ supplements, 2-3X a day.  And every 2 weeks I’m rotating all of it to prevent antibiotic resistance.  In another month I plan to retest myself and make the necessary adjustments to my protocol.  

This person sent a request just after this post went out: My gut has gone to Firmicutes!

Reader’s Backstory

I am a 39 year old male from the US whose symptoms appeared at or around the time of puberty.  My case is not particularly severe – in fact it took me until the age of 23 to acknowledge to myself that I had a problem. While I fit the diagnostic criteria for ME/CFS, I specifically suffer from brain fog, low mental and physical energy, food sensitivities, 3 trips to the bathroom each morning, mild joint pain, and unrefreshing sleep. My symptoms have gradually worsened as I’ve aged. Certain vitamins, herbs, and foods have helped me to feel better but these solutions do not last more than a few days max. Nobody else in my family shares my symptoms, and I’m told I didn’t take antibiotics as a child.  My BMI is 22.

Proforma Review

Well you can see the process in this My gut has gone to Firmicutes! post, I thought that I should do a step by step walk thru of the process that I use.

After logging in, I go to [My Profile] and then on the [Overview] panel, click Health Analysis.

Under Potential Medical Conditions Detected, there were no red flags (see 📹 Explaining these measurements).

Similarly, [Bacteria deemed Unhealthy] had no red flags but does have a few bacteria that are not healthy predictors (Eggerthella lenta, Blautia producta, [Clostridium] symbiosum) and Collinsella (90%ile) which is viewed as proinflammatory – not unexpected with ME/CFS. Dr. Jason Hawrelak Recommendations came in at 98.8 percentile, so generally healthy. Blautia is of interest, it is at 36% of the microbiome versus Dr. Harelak preferred 5-10% and one of the highest levels in over 3,000 samples. This seems to be a possible smoking gun. The person is at the 70%iles using PubMed studies for ME/CFS without IBS.

Using the Krona Chart panel we see that the dominant species is Blautia obeum (which lacks any clear condition associations).

The next step is to look under [Visualizations] – Microbiome Tree, to visually scan for unusual disturbances. What I usually look for on the first pass are HIGH Percentiles with a high % of the microbiome. 💥BOOM we had some major ones. The 100%ile means that the value was higher than any of the 3000+ samples

Taxa / BacteriaPercentilePercentage
Firmicutes phylum96%ile97.7%
Eubacteriaceae:99%ile7.7%
Eubacterium99%ile8.1%
Collinsella aerofaciens91%ile1.3%
Blautia100%ile36.2%
Blautia obeum100%ile21.3%
Dorea100%ile7.7%
Dorea longicatena100%ile6.5%
Agathobaculum99%ile3.1%
Agathobaculum desmolans99%ile3.1%

At this point, we have a ton of items that are overgrowth. This is a very atypical sample with a bunch of unusually high shifts. So we will move on to getting suggestions.

Bacteroidetes is 0.43% of the microbiome so we are talking a Firmicutes/Bacteroidetes ratio of 228:1. The normal ration is around 1.5 (The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age, 2009), There is also considerable variation across the world.

The Firmicutes/Bacteroidetes Ratio: A Relevant Marker of Gut Dysbiosis in Obese Patients? [2020]

If there was not so many extreme high values, then our suggestion process usually work with both high and low values.

Getting Suggestions

My usual process is doing three methods and looking at the consensus report. The methods are:

Because of the extreme values, I am also doing Percentile in top or bottom 5% [28 taxa picked], For all four of these, I am restricting the suggestions to High Items. We need to reduce bacteria to make room!

The list was interesting — and also typical for ME/CFS patients:

The high-protein/meat diet would also provide B-vitamins listed above. Hesperidin’s best natural source is lemons — which also will provide Vitamin C. The best source for Arbutin is likely Lingonberry (available at IKEA) – for other see Arbutin – Microbiome Prescription Food And Nutrients. For the top items, use Nutrients with Number of Foods – Microbiome Prescription Food And Nutrients to see what foods contains it if you wish natural sources (or as supplements is not available).

There is one interesting diet to consider: Eating traditional Indian (based on chart above) – i.e. meatless high spice diet consisting of a lot of Dal and other foods from Taste of India or Kitchens Of India. Alternatively, spend 6 months at a traditional Ashram in India. This diet appears to result in the lowest Firmicutes/Bacteroidetes ratio.

Probiotics

While there were a few suggestions, the computed impact were relatively low compare to those with negative impact. I would skip probiotics.

Questions from Reader

Q: Does the Consensus View only show me what to increase, or does it also show me what to avoid? 
A: Yes, Just click on the column titles to reverse the order. If you hold the shift key, you can do sorting by multiple columns.

Q: This may seem like a silly comment, but it’s difficult for me to envision a vitamin (such as B1) or a supplement (such as melatonin) significantly influencing the microbiome. I picture large foods filled with bacteria like sauerkraut, or sugary foods like cookies, as the items that would have the biggest impact.  I clearly have a lot to learn.

A: Bacteria feed on chemicals, including vitamins. If you click on the modifier name, i.e. thiamine hydrochloride (vitamin B1), AFTER setting display level to Intermediate, you will see a column called citations:

Clicking on Source Study will show where the data is coming from, with links to the studies.
Some studies are on animals — but the bacteria is expected to respond in the same manner.

Remember: The site works off of actual peer-review studies only. Evidence, not speculation or wishful thinking.

Q: When I adjust the recommendations to include prescription items, I get a whole bunch of prescriptions that show up.  I’ll try to convince my doctor to prescribe!
A: It is not worth the effort — because this is an off-label usage and there will be resistance. Especially since half of the top items in the list are not prescription and similar predicted impact. Hesperidin is in Lemons and Buchu, no prescription needed. Try the other items first, if the next test shows improvement (expected) and a prescription item jumps out far above the others — then it will be a good time to ask.

Q: Random question:  The Probable Symptoms link under My Profile seems to be broken at the moment.  This isn’t the same as the Potential Medical Conditions Detected under the Health Indicators, right?  
A: Correct, the probable symptoms is done by pattern matching. Your numbers are so different that the A.I. was unable to make a reasonable infererence.

Q: I’d think the microbiome would be a really accurate way to predict obesity, but under Potential Medical Conditions I was surprised to see i’m in the 100th percentile for Obesity.  I weighed 120 pounds throughout high school and even now can’t break 150 lbs.  I plan on getting updated samples every couple months, so i’ll be interested to see if my next sample shows something different here.
A. Once we get things changing, we can use the National Library of Medicine Citations for Obesity to see how we want to target further shifts. We know what bacteria is associated with it, we just want to push the same bacteria in the opposite direct from that which was reported.

Course of Action

The first item of concern is simple: make sure that the dosages are adequate to effect changes. Taking a once-a-day supplements that has all of the vitamins listed above is unlikely to have any significant effect. Use the Dosages for Supplements to find the dosages. This can also be found by clicking on the Simplified Suggestions

Quick summary of dosages

After 4-8 weeks (depending on finances), repeat the microbiome test (using the same lab) and see what has changed. Recovery is like steering a sailing ship: it is a continuous set of course correction. Sometimes just a few to get to a safe harbor; other times, you may feel like you are circumnavigating the world.

Literature on ME/CFS and Firmicutes: I review studies on ME/CFS, Chronic Q-Fever, Lyme etc, and I do not find this pattern being cited. It is a very big 💥 BOOM pattern

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.

The information above should always be considered/discussed with your medical professional if possible.

My gut has gone to Firmicutes!

Back Story

I am a 25 year old male from the US, and I have been suffering from constipation, food sensitivities, insomnia, and psoriasis since 2018 (21 years old) after a round of Clindamycin.

This person actually has three samples from OmbreLabs:

  • 2022-09-09: Firmicutes 95% (93%ile)
  • 2022-10-01: Firmicutes 93.5% (88%ile)
  • 2022-11-10: Firmicutes 94.8% (90%ile)

The first thing that I note is that “give it time, it will correct itself” does not seem to be happening. The second thing is these rates appear to be seen in about 10% of the samples.

Drilling down to which Firmicutes are dominating we have (latest sample):

My first impression is that we want to focus solely on reducing the high ones, and make room for the low ones to grow. That is actually a choice on building a consensus. Because of the shear numbers, I am going to use strict study citations. Why? Typically we are sparse on studies and need to infer / estimate likely impacts. In this case, we are going to hit studies everywhere!

For bacteria selection (with only highs) we have:

  • Filter by Standard Lab Ranges – 14 bacteria
  • Kaltoft-Moltrup Ranges – 50 bacteria
  • Box Plot Whiskers Ranges – 58 bacteria

The list of items suggested is atypical with supplements dominating! I attach them below.

PriorityGut Modifier
795.9Hesperidin (polyphenol)
789.3melatonin supplement
774.7luteolin (flavonoid)
774.7retinoic acid,(Vitamin A derivative)
774.7Arbutin (polyphenol)
774.7diosmin,(polyphenol)
774.7vitamin b3 (niacin)
774.7pyridoxine hydrochloride (vitamin B6)
709.2thiamine hydrochloride (vitamin B1)
688.7vitamin b7 biotin (supplement) (vitamin B7)
687N-Acetyl Cysteine (NAC),
656.3linseed(flaxseed)
642.7Vitamin B-12
592.7caffeine,(coffee or non-herbal tea)
563tea
522neem
506.5quercetin,resveratrol
495.6folic acid,(supplement Vitamin B9)
455.7Guaiacol (polyphenol)
438.6low carbohydrate diet
428.5carboxymethyl cellulose (prebiotic)

My suggestion would be a low carbohydrate diet and start taking the supplements above. I would avoid all probiotics, one did show up at the top of the probiotics: bifidobacterium longum bb536 (probiotics) at the strain level, but a strong avoid at the species level which means it is a high risk one

I would use the suggested dosages cited below (AFTER reviewing with your medical professional)

Microbiome ModifierCurrentDosageClinical DosageEst Confidence
Vitamin B1 Thiamine1.8 gm/day709.2
Vitamin B3 Niacin3000 mg/day774.7
Vitamin B6 Pyroxidine200 mg/day774.7
Vitamin B7300 mg/day688.7
Vitamin B9 Folate5 mg/day495.6
Vitamin B12 Cyanocobalamin10 mg/day642.7
Vitamin C30 g/day410.7
Vitamin D50000 UI/day141.3
DO NOT USE A B-COMPLEX. Some B-Vitamins were to be avoided

Questions From the Reader’s Review

In general, I avoid diet styles personally because they lack precision for the content. For example, does doing a Mediterranean diet means drinking the typical amount of wine (10-12 liters of wine per year) with 57 pounds of fish a year as seen by many countries around the Mediterranean? The fish consumption in the Mediterranean region differs greatly from what is claimed to be from that diet.

  1. What exactly is meant by a low carb diet in the research? (50 grams, 100 grams, etc)
  2. I see that sorghum is recommended despite being a carb source (this is further in the consensus suggestions, but on in the blog post), so would this be a high risk item?
    • Suggestions are done independent of each other. In general, we have no idea about interactions. As with all suggestions, the source of the suggestion is available, in this case it was specific for sorghum brans [2015].
  3. Vegetable/fruit juice based diets is one of the diet styles recommended.  Would perhaps following a diet low if solid carbs like rice, bread, potatoes but still consuming orange juice be an idea worth considering?  Getting carbs from juices would essentially prevent any food residue from getting far into the digestive system; therefore, limiting fermentable residue.  I am asking so much about carbs because I have done low carb in the past, and I felt better for a short period of time but worse long term.
  4. How long should the low carb diet be followed?  How strict do I have to be to receive benefits?
    • Suggestions are usually safe to keep to for 4-6 weeks, then their impact on the microbiome should be realized and a retest should be done to get the next course adjustment.
  5. How safe is carboxymethyl cellulose as a prebiotic based on the research?  I am a little concerned about taking it.  I also have a capsule making kit, so I would be able to make my own capsules.
  6. Chitosan has a fairly high at 407.3 on the consensus.  Is there a reason for not including it on your list in the blog post.  I see that one of your posts from CFS remission seem to recommend it for firmicutes overgrowth.
    • The reason to include or exclude is actually shown on the Advance Tab, see below

Getting the Reasons for Suggestions

  1. Change Display Level to Advance
  2. Go to Research Features tab
  3. Find this section and click Advance Suggestions

On the next page select how you want to generate suggestions and then make sure you click the green box

On the next page you will see book stacks (📚) by each suggestion.
Click it:

This will show the studies used to make this decision and why. That is, what are the other bacteria impacted by using this chitosan. Note that there are 42 taxa-studies listed! Focusing on a single bacteria, like firmicutes is not a process that I encourage, that is why I let the AI determine the suggestions based on all of the facts available.

Foods

If you pick a diet type, then using the new experimental food component would be suggested as an adjunct tool. I used the KM filter, restricted only to high bacteria as a start point for foods.

At the bottom of the suggestions page, we see the link button

The top items (with nutrients they were selected on) are listed below:

On the avoid list:

The food list takes items like Hesperetin and vitamins, and show the foods higher than typical. It speeds the analysis (and also overload the data that you have).

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.

The information above should always be considered/discussed with your medical professional if possible.

Samples over time of ME/CFS Spouse

This is the spouse of someone with significant ME/CFS. It is well known that bacteria is transferred between people in the same household unit.

This raises all sorts of questions — which I am not interested in exploring… “For better or worse, in sickness and in health”

My wink wink suggestion for microbiome issues has been “Snog a lot of pretty young healthy things as the best probiotic” — my wife does not agree…..

Comparison between Samples

The first step that I did was to verify that all samples used the same reference sticks. This means clicking this for each sample first.

New reference tables are uploaded once a week.

This person has processed FASTQ data thru both BiomeSight and OmbreLabs. I am using OmbreLabs data below. Using reference tables uploaded in 2023.

Criteria6/8/20228/4/20229/6/202210/26/2022
Lab Read Quality2.13.83.68.3
Bacteria Reported By Lab534774721775
Bacteria Over 99%ile10326
Bacteria Over 95%ile58272422
Bacteria Over 90%ile99534450
Bacteria Under 10%ile256848127
Bacteria Under 5%ile13281577
Bacteria Under 1%ile53116
Lab: Thryve
Rarely Seen 1%814912
Rarely Seen 5%43806073
Pathogens21343327
Outside Range from JasonH5577
Outside Range from Medivere13131717
Outside Range from Metagenomics9999
Outside Range from MyBioma7788
Outside Range from Nirvana/CosmosId23231919
Outside Range from XenoGene44444949
Outside Lab Range (+/- 1.96SD)38392622
Outside Box-Plot-Whiskers177202153118
Outside Kaltoft-Moldrup206257203292
Condition Est. Over 99%ile0000
Condition Est. Over 95%ile0000
Condition Est. Over 90%ile0000
Enzymes Over 99%ile1418523
Enzymes Over 95%ile11510559112
Enzymes Over 90%ile212192143320
Enzymes Under 10%ile6310693266
Enzymes Under 5%ile294527141
Enzymes Under 1%ile2208
Compounds Over 99%ile373631119
Compounds Over 95%ile289288275281
Compounds Over 90%ile372381361385
Compounds Under 10%ile288255235298
Compounds Under 5%ile192159136216
Compounds Under 1%ile3714431

General Impression

  • After the first sample, the next two had improvements but the last one went the wrong way.
    • Too high and Too low reduce for 2 samples and then increased
    • Too high or too low for Enzymes were the highest for the last sample
  • Most of the third party ranges were constant for the first two samples and most got worst for the last two samples.
  • Compounds are much less indicative of issues.
  • Special Studies are sensitive to lab quality,
    • 6/8/2022 4-14%, top items: ME/CFS without IBS, Poor gut motility, Cold Extremities
    • 8/4/2022 5-17%, top items: ME/CFS without IBS, Poor gut motility
    • 9/6/2022 4- 18%, top items:  ME/CFS without IBS,  Easily irritated
    • 10/26/2022 7 -22%, top items: General: Fatigue, ME/CFS without IBS

ME/CFS without IBS is a consistent top item and we see that the percentage is increasing.

Proposed Approach

Unlike many samples, we see distinct deterioration in several 3rd party criteria. For many samples, there is no change between samples. We will include those in the consensus, namely:

  • JasonH
  • Medivere
  • MyBioma
  • Xenogene

It is interesting to note that one 3rd part criteria improved: Nirvana. To this, we do our usual:

  • Lab ranges
  • Box-Plot-Whiskers
  • Kaltoft-Moldrup

The net result will be more bias to those in the 3rd party criteria cited above. Another way of stating that, we will emphasis more that which everyone agrees are most concerning.

The top suggestions (easily obtained):

The top avoids are:

The downloads are attached:

Food Suggestions

We mostly eat pastured meats and vegetables. No cereals and little in the way of carbs or even fruit. I used to eat linseed crackers in the USA, but here I eat buckwheat instead. Here in Spain we switched from wild Alaskan salmon, to seasonal, local, small blue fish, like mackerel, sardines, etc. Added Rabbit and can eat a lot more quality raw cured pork, if we want to. I have always enjoyed natural wine and Spain has plenty of it. Fresh made coffee and 100% cocoa. Raw goat, sheep and cow’s milk are also available and I do enjoy them with some regularity.

I used the latest sample with the Kaltoft-Moltrup Normal Ranges. The top suggestions are each because of different nutrients that appear significant with Fiber, total dietary and Magnesium, Mg being a common theme.

On the avoid list we have at the bottom:

Remember, foods are filtered to the nutrients that are above typical levels for foods containing the same nutrients. The goal is to reduce the intake of nutrients that have been identified to shift things in the wrong direction.

For most people, if you say reduce folic acid in your diet — most people will not have a clue. The purpose of the food suggestions is to translate a precise item into common foods.

Note: If a food in your diet is not in the list then we deem it as neutral. For example: there are 24 variety of rabbit in the food database, only one shows up in the suggestions from the sample, Rabbit, meat, raw, Oryctolaguscuniculus, (Nyama ya kalulu), which suggests to keep eating rabbit. Similarly for milk, the two that shows up are Milk with Cow’s blood (from Africa) of 626 entries for milk.

The video below may help understand Food Suggestions better.

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.

The information above should always be considered/discussed with your medical professional if possible.

Babe’s gut destroyed at mother’s breast..

Facebook Messages

Original From April

You seem much more switched on than some of the functional doctors I have used

He’s already on anti histamine 🙁 (ketotifen) [Editor: which decreases most bacteria]. He has been on it 7 months. It initially helped with foods but now I find it makes him irritable and tired all the time. He obviously has allergies and the doctors here don’t care obviously 🙁. Well I feel it’s made him a lot more irritable. It’s helped with sleep but that’s about it. He has the erratic mood swings and he’s worse for me.

I am worry that he has PANDA.

He had 3 lots of baby vaccines I do think he got worse after each. But I’ve skipped his one year vaccines. He was given omeprazole for acid reflux 🙁 [Editor: it also decreases many bacteria and only increases Actinomycetales]. I stopped it after a few months because it made him worse

Hi Ken, hope you are well. We have introduced Oats and also apple to the diet. All is going ok…. until I gave some papaya. Ever since we have had sickness and orange diarreah….. any ideas? We stopped papaya, 2 days ago. Someone suggested we try papaya ages ago as it is soothing. Obviously not for sonny, given him sickness and diarrhea.🙁

He has very high levels of lactobacillus

He has banana and oats now and apple. We have had to pick him up from nursery because of his diarrhea🙁. Maybe he does have a bug… [Response give him a few days to recover]

5 May 2022

I think you’ve saved my life. My little boy is so much happier

Need to find a protein to go with the oats so he doesn’t get the spike in carbs so much now

[Response: Walnuts?] We have not tried those. May try grounded walnuts 🙂.

[Response: Walnuts and Oats/Barley often show up together in suggestions.]

Other carbs? Cous cous, sweet potato, pasta? [Response: Without data from a 16s microbiome sample, IMHO, playing russian roulette.]

Nov 17,2022

Ken…. You helped me massively before. My son will be 2 next month… his gut issues are so bad it’s making his behavior / anxiety awful. He even reacted to homeopathy, he went 3 days without a poop. He’s got so much inflammation / bacteria out of whack I can’t get it under control. No official diagnosis other then dysbiosis and heavy metals I’m in the UK

His current diet:

  • 3 x 7oz bottles of formula milk – nutramigen
  • Wild salmon or lamb
  • Broccoli
  • Zucchini
  • Green apple
  • Gluten free porridge oats
  • Parsnips
  • We’ve been using colostrum too. Not sure if that’s similar to hmo [Response: It is not]

Last Microbiome Report was done by Invivo. Every commensal bacteria but one was flagged as out of range. Unfortunately, this report does not reported relative amount but some proprietary scale.

I think he started off sensitive from me. Then I breast fed him whilst I had antibiotics then the doctors gave him antacids.

Analysis

The history keeps echoing the same theme, the infant microbiome has been hammered for the last two years. As a starting point, what should a 2 year old healthy child look like?

From Robust variation in infant gut microbiome assembly across a spectrum of lifestyles [2022],

Clearly we see:

  • Too few bifidobacterium/Streptococcus
  • Too low blautia
  • No reported Prevotella, low Faecalibacterium prausnitzii

We limited appropriate information on the microbiome (I would strongly suggest using the UK firm Biomesight for the next microbiome test), but the model is pretty simple — somehow encourage a microbiome typical for a 2 year to develop.

My first concern is raising bifidobacterium. To me, that means a Human Milk Oligosaccharides (which may be challenge to get — could not find any on Amazon.co.uk. You may wish to contact Glycom in Denmark to see if they can assist. The second part also comes from the above article, Bifidobacterium infantis probiotics (“a prolific utilizer of human milk oligosaccharides (HMOs) that is positively associated with human health”). The suggestion on Custom Probiotics of 5 BCFU of this specific probiotic for a child is likely a good start. BEWARE of mixtures – unless it is the first ingredient then the amount may be ineffectual. Both of these may be challenges to get in the UK.

Differences in the species composition and HMO-degradation genes of the initially dominant Bifidobacterium communities are especially relevant as recent studies of these same genes suggest that their depletion in industrialized infants could have long-term negative immune consequences (Bifidobacteria-mediated immune system imprinting early in life [2021])

Robust variation in infant gut microbiome assembly across a spectrum of lifestyles [2022],

He has high E.Coli, given his age, my first thought go to Symbioflor-2. It is droplets (normal adult dosage is 18), so you can start with just one drop in a glass of water and slowly work up the dosage. While it is an E.Coli bacteria, it is a good E.Coli that should outcompete some of the bad E.Coli.

https://www.paulsmarteurope.com/symbioflor-2-tropfen-drops-50ml-bottle/

The last item that I would consider are some bacillus probiotics. These are often picked up from grass and fields (“the wild”). There are many listed here. Considering the allergy/histamine issues, I would avoid those that are known histamine producers.

Make one change at a time, no more than one a week.

Update with Current BiomeSight Data

Looking at Bacteria deemed Unhealthy, one item stands out: Clostridium which is at the 98%ile while only 5.5% of the sample. Dr. Jason Hawrelak Recommendations (does not include Clostridum) we see two items of special significance:

Looking at the Clostridium, we see that the species causing the high number was not identified.

For Akkermansia, the species identified was Akkermansia muciniphila.

I did a hand picked set of suggestions using only these two, the suggestions are below:

I then ran the sample thru the new experimental food suggestions to see what foods are suggested. The most interesting takes are:

  • Grape pure juice
  • For meats: none of the top recommended are available – the are all game meats (caribou, reindeer, elk, and seal lion)

I then did the usual 3 computed ranges (Standard Lab Ranges (+/- 2 Std Dev), Box Plot Whisker, Kaltoft-Moltrup Normal Ranges ).

The results from these are similar:

The full set is attached below

Changing to the experimental food suggestions, we see the top items being:

The full list is attached. For many of the foods, we see this pattern for why the food was directed

For items further down the list we see sugars are not there, and a variety of vitamins, etc

Baby cereal, containing milk, 12months, strawberry flavor, dry

Reminder: For food suggestions, it is wise to jump up and down the list for various net-values. Most items with the same value are likely selected for the same nutrients in it.

Feedback from Reader

She expressed the opinion that the solution to the  Clostridium is just taking Saccharomyces boulardii. That is may help reduce is supported by two studies:

This is not major evidence, because one of the Clostridium family, Clostridium difficile has been extensively studied. A Prevention of recurrent Clostridioides difficile infection: A systematic review of randomized controlled trials [2020] study cites that Saccharomyces boulardii and  oligofructose was efficacious for rCDI prevention, but not for treatment. The oligofructose is in agreement with the grape juice and other fruites cited above. This is echoed in “Saccharomyces boulardii has shown effect as a prophylactic agent. ” [12].

If we look at probiotics studied for Clostridium, we see 112 studies; most for Clostridium difficile – especially prevention when antibiotics are taken. Florastor®(Saccharomyces boulardii CNCM I-745) is the only one studied that is available in the retail market. Other cited are Bacillus clausii, Bacillus coagulans, Bacillus mesentericus, Lactobacillus rhamnosus GG etc. Almost all of the studies are for prevention and not for treatment. In other words, it helps create an unfriendly environment for C.Diff. but appears to be in effectual fighting it.

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.

The information above should always be considered/discussed with your medical professional if possible.

Mast Cell Moderators — non-drugs and suspect bacteria

In discussion with readers, interest in non-drug treatment of mast cell and histamine issues is very high. Trying to get traction with the microbiome has not been successful. On how to use Half-Life, see Half-Life: Not the game but supplements! For Arginine and Glutamine, 100mg of each every hour is suggested.

Dosages: Are the maximum deemed safe by an authority, not recommended dosage

Reflection into the Microbiome

Most of the items above are modifiers on Microbiome Prescription. An interesting experiment is to see which bacteria/taxa are modified in common with the above. Below are the taxa that occurs 6 or 7 times for the above 7 items.

Taxa NameRankImpactTimes Shared
BacteroidaceaefamilyDecreases7
LachnospiraceaefamilyMajor Decrease6
DesulfovibrionaceaefamilyMajor Decrease6
ClostridiaceaefamilyDecreases6
BacteroidesgenusDecreases7
FaecalibacteriumgenusIncreases6
RuminococcusgenusDecreases6
DesulfovibriogenusDecreases6
RoseburiagenusDecreases6
EubacterialesorderDecreases6
Bacteroides xylanisolvensspeciesDecreases7
Bacteroides caccaespeciesDecreases7
Bacteroides ovatusspeciesDecreases7
Bacteroides uniformisspeciesDecreases7
Bacteroides thetaiotaomicronspeciesDecreases7
Phocaeicola vulgatusspeciesDecreases7

Items that are marked decreases, are likely bacteria you may want to reduce if you have mast cell issues. Faecalibacterium is the one bacteria that you want to increase.

Applying to your microbiome sample

On the [Research Feature] tab. Find this section and click #2

See Video above for the rest of the steps

As always, review your plan with your knowledgeable medical professional before starting. Some substances may be inappropriate for other medical constraints.

Half-Life: Not the game but supplements!

This week I have been pinged by several people with ME/CFS who have seen drops in Saturated Oxygen Level (SO2) during the day. One model of many symptoms of ME/CFS (brain fog, easy fatigue) is that of diminished oxygen deliver and reduced products clearance (like CO2 and Lactic Acid). This reduction of oxygen can be due to many causes: Coagulation, Inflammation, Hemoglobin (iron) disruptions, etc.

Long COVID: This also applies here, “Tiny, Menacing Microclots May Explain Long COVID’s Symptoms

People who follow me knows, know that I prefer to work from facts, models and objective measurements. Saturated Oxygen Level (SO2) gives us an objective measurement. Personally, my wife and I use a smart watch that records my (SO2) and other factors every 10 minutes. The data has been helpful to us to triage some events — it is not a Star Trek Tricorder, but better than speculation. Images at end of the data.

Importance of Half Life

What is called half-life is actually critical for dosage size and timings. MDs prescribing drugs specify one tablet a day, two tablets every 12 hours, a tablet every 8 hours; are based on half-life typically.

What is half-life? It is simply the time it takes to reduce the level in the body to half of the prior amount.

This is not always simple, it takes time to get the supplement or drug into the body as the following quote indicates:

“In healthy volunteers who have taken oral doxycycline, the maximum doxycycline plasma concentrations (Cmax) of 1.5 to 7.0 μg/ml are usually reached within 3 h, and the drug has a half-life of 14 to 24 h” [2005]

Step One — Find Half Lifes!

This is actually pretty easy, usually typing in the supplement and “half-life” will return answers from the web. For the above people, I assembled a list of possible testing supplements from prior posts on coagulation to see if we can determine the possible mechanism for the SO2 drop they saw. The purpose is to identify a probable cause which should then be discussed with your medical professionals.

See this post for the literature on these. We want to then find the half-life and the maximum safe dosage. Many of the maximum deemed safe (i.e. used in studies dosages) are listed here.

SupplementHalf LifeMax Dosage
Alpha Lipoic Acid30 minutes [Full article: Alpha lipoic acid intoxication, treatment and outcome (tandfonline.com)2400 mg/day (see Src)
Aspirin3 hours at lower doses (300 to 600 mg), 5 to 6 hours (after 1 g), 10 hours with higher doses [source]4000 mg/day [Aspirin Dosage – Drugsdb.com]
Grape Seed Extract / Resveratrol2-5 hours [source]
2000   mg/day
Nattokinase4-6 hours [source]
14,000   fibrinolytic units/day
Lumbrokinase 8.6 hours [source]1470   mg/day
 SerrapeptaseCould not find30   mg/day
Boswellia Gum6 hours4800 mg/day [src]
Bromelain6-9 hours2000 mg/day
 Piracetam5 hours
24000   mg/day
 Turmeric6-7 hours3000 mg/day
Licorice3.5 hours32   g/day
 Ginsengn/a2000 mg/day
Coenzyme Q1033 hours1200   mg/d

As above, there can be time to get it into the body as the following states for CoQ 10.

The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ10 in large doses is taken up by all tissues including heart and brain mitochondria. 

Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics – PubMed (nih.gov)

This is a useful exercise to do for ALL OF YOUR SUPPLEMENTS. This will answer the question, should you do one mega dose a day or 4 small dosages thru the day or even 6 or 8 small dosages per day – to get the best results. You want to maintain a reasonable level in your body for the whole day.

One possible strategy

There are many possible approaches, my preference here would to start with the longest half life and work down. This leads to the following suggestions (to be discussed with your medical professional)

  • CoQ10: 300mg day 1, 600 mg day 2, 900 mg day 3, then 1200 mg/day for at least 2 weeks.
    • 4 capsules per day for some products
  • Bromelain: : Given the half life, I would start with 1 capsule every 12 hours (typically 500mg), doubling the dosage on the second day and then keep repeating for the rest of the week
  • Lumbrokinase: Given the half life, I would start with 1 capsule every 12 hours, doubling the dosage for the next 4 days keep repeating for the rest of the week
  • etc

You want to identify the substance that hints at the source, then get your MD involved. Do not try all of them at once. Introduce one item a week and see what the response is. Personally, I did the Aspirin route which had me running up and down the walls after 7 days — that response persuaded the MD to order the Hemex Lab Coagulation Panels which identified issues. That lead to appropriate treatment.

For the short half-life items, You want to take a SO2 measurement no longer than the half-life. For Alpha Lipoic Acid, the typical capsule is around 300 mg, so I would go for one capsule every hour for 4 hours and monitor the levels for at least 6 hours. This will keep the concentration at a reasonable level. Going above the maximum dosages has significant risk. This is an example for ALA, Alpha lipoic acid intoxicatıon: An adult [2018]. As always, have your plan reviewed by your medical professional before starting.

Remember: Record in Excel or other product your base line — the daily or weekly pattern before you start. Keep up the recording of SO2 as you walk thru the substances. For me, having a smart watch that does it makes it so so easy with awesome data to show my MD.

Addendum: DAO – diamine oxidase

This is a troublesome one — with two answers!

If DAO is being taken to reduce histamine in the body – we use 18 hours. If it is being taken to quiet down the histamine release in the gut from eating something, it is 19 minutes. So, taking DAO immediately before or during a meal may have the best benefit.

The Unique Possibility of Symptom Treatment Resolving the Cause

My model of coagulation issues is simple: some group of bacteria are dumping chemical signals into the body that triggers one or another form of coagulation. Why would they be doing that? Survival! These bacteria prefers a low oxygen environment so they are taxa-forming your body for their needs. Increasing the oxygen level in the body will typically inhibit these bacteria – but may not be enough to suppress them. The use of other substances (in the personal experience that I cited above, following Cecile Jadin’s “Occult Rickettsia” protocol of rotating antibiotics) may be needed to suppress these troublesome bacteria, to “rid me of this meddlesome taxa”. Note: The virus or bacteria that trigger the illness is unlikely to be the meddlesome ones, rather, other bacteria that saw opportunity in its disruptions of the body and exploited it. I believe these bacteria are seen in stool microbiome samples.

Example of the recording on the Smart Watch of Oxygen Levels
Example of Temperature —

2023 Walk thru of Personal Microbiomes Suggestions

The two videos below are intended as quick introductions to the microbiome prescription site. The site is dynamic with continuous changes of data available and being used.

See also: A series of online meeting on using Microbiome Prescription [Sep 2023] update. Likely a better start point.

16s Samples

This covers sites that provides comprehensive reports on your microbiome. The better reports typically report on over 500 different bacteria from a sample.

Lab/ProcessorLowTypical CountHighSamples Uploaded
AmericanGut7315621318
BiomeSight1157213051635
BiomeSightRdp27957386215
CosmosId643670536
es-xenogene5761522524
Medivere5307219347
Microba5312618621
OmbreLabs/Thryve18567122381241
SequentiaBiotech16631346036
uBiome6249589814
Statistics at the start of January 2023

Older Labs

These are older technology and often are focused on a small number of bacteria. Often the focus was based on what was deemed significant 10 or even 20 years ago.

Lab NameSamples
Viome (No objective measures) 5
All Taxonomies from tests 67
Medivere: Gesundsheitscheck Darm (16s Limited) 15
GI360 Stool (UK) 29
Medivere: Darn Magen Diagnostik (16s Limited) 15
All Bacteria [Family] Reported 25
Smart Gut (ubiome 16s – Limited Taxonomy) 2
GI EcologiX (Invivo) 19
GanzImmun Diagnostics AG Befundbericht 14
DayTwo 8
GanzImmun Diagnostic A6 (cfu/gm) 80
Nordic Laboratories 2
InVitaLab (cfu/gm) 3
Biovis Microbiome Plus (cfu/g) 18
Diagnostic Solution GI-Map (cfu/gm) 498
Metagenomics Stool (De Meirleir) (16s Limited) 4
Genova Parasitology (cfu/g) 4
Verisana (cfu/ml) aka (kbe/ml) 2
Medivere: Darm Mikrobiom Stuhltest (16s limited) 12
Genova Gi Effects (cfu/g) 116
Kyber Kompakt (cfu/g) 2
All Bacteria [Genus] Reported 188
Bioscreen (cfu/gm) 13
NutriPATH 12
Gut Zoomer (vibrant-wellness) 6

New Food Features

This feature was added because many of the suggestions were for flavonoids or other items that may or may not be available as supplements. Most people do not know what is in different foods, especially items you are wishing to avoid. The intent is to allow a more comprehensive and rich diet to be developed by users.

Crohn’s Over Three Years

This is a reader with a diagnosis of Crohn’s diseases with complications (severe histamine and mast cell issues, severe multiple chemical sensitivity). She also have had ongoing hot flashes for a few decase The Crohn’s has been stabled and does not require prescription medications; it has been treated by diet and the use of E.Coli probiotics (Symbioflor-2: SOURCES: https://www.paulsmarteurope.com/ and https://www.naturitas.us/, and Mutaflor). When a flare starts, the E.Coli probiotics have been able to quiet things down quickly.

Using the new Food Suggestions (with consensus)

This is a new feature that is intended to supplement the first class suggestions from microbiome prescription. Almost 8000 different foods are evaluated. The intent is to allow people to fine tune diets for the most impact especially when flavonoids and sugar types are given by name, but not by what food contains them. Some foods may have both good and bad content, the intent is do a deep evaluation of the foods based on their reported nutrients. For more information, see this blog post.

Overview of Samples

The general impression of the samples is reasonable stableness. Some third party criteria improved (Metagnomics, Xenogeme) and other third party criteria (Medivere,MyBioma,Nirvana) got worst, and one with no change(JasonH). The same is seen with the statistical ranges.

Criteria202220212020
Lab Read Quality34.13.8
Bacteria Reported By Lab524584721
Bacteria Over 99%ile596
Bacteria Over 95%ile304436
Bacteria Over 90%ile528284
Bacteria Under 10%ile452526
Bacteria Under 5%ile15104
Bacteria Under 1%ile000
Lab: Thryve
Rarely Seen 1%849
Rarely Seen 5%272951
Pathogens293328
Outside Range from JasonH777
Outside Range from Medivere151514
Outside Range from Metagenomics101012
Outside Range from MyBioma131312
Outside Range from Nirvana/CosmosId232314
Outside Range from XenoGene404049
Outside Lab Range (+/- 1.96SD)312218
Outside Box-Plot-Whiskers138109142
Outside Kaltoft-Moldrup184163205
Condition Est. Over 99%ile000
Condition Est. Over 95%ile121
Condition Est. Over 90%ile121
Enzymes Over 99%ile390
Enzymes Over 95%ile326423
Enzymes Over 90%ile6519471
Enzymes Under 10%ile1364568
Enzymes Under 5%ile422137
Enzymes Under 1%ile040
Compounds Over 99%ile261421
Compounds Over 95%ile1222929
Compounds Over 90%ile3503837
Compounds Under 10%ile1492422
Compounds Under 5%ile311718
Compounds Under 1%ile466

Looking at Special Studies:

  • 2020 – 7%- 21% matched, 38%ile against PubMed Criteria
  • 2021 – 5% – 18% matched, 32%ile against PubMed Criteria
  • 2022 – 5% – 16% matched, 74%ile against PubMed Criteria

The top common ones across the years are:

  • Poor gut motility
  • ME/CFS without IBS
  • Easily irritated
  • Post-exertional malaise
  • Depression

We do not have sufficient samples yet to do a special study for Crohn’s disease.

There appears to be a weak indication of worsening — this may be due to not being able to get Mutaflor (E.Coli Nissle 1917) during COVID restrictions. This was remedied shortly after the last sample.

Going Forward

Doing the usual three statistical methods (Standard Lab Ranges (+/- 2 Std Dev),  Box Plot Whisker, Kaltoft-Moltrup Normal Ranges) to get suggestions (including prescription drugs). I included prescription drugs to see if any typical Crohn’s drugs are suggested.

  • risperidone: was the top one, this is used to treat mood disorder (depression and irritability bacteria?)
  • hexestrol:  a nonsteroidal estrogen which was previously used for estrogen replacement therapy (hot flashes)
  • ethopropazine hydrochloride: a drug uses for Parkinson’s disease. A blood family member had Parkinson’s and the person has seen the occasion “shake” in her hands that has raised concerns about that condition
  • The next items were antibiotics and significantly less confidence.

This is not totally surprising that prescription items appear to match conditions. The mechanism of action of these prescription drugs may be partially thru the microbiome.

Returning to the non-prescription world, in terms of priorities:

In one sense, the reader was very pleased with these suggestions being almost entirely supplements. The histamine issues greatly restricts her food choices (she is already gluten free!)

Food Suggestions

I did a walk thru of the food suggestions for this sample. See the video below.

Experimental Food Suggestions

Presentation on What we are doing

This is a short video on the process

Sources of Data

How to Use

Go to Microbiome Prescription, log in and go to [Changing Microbiome]. At the bottom of each section you will see a check box. Make your usual selection and then check this choice and click [Get Suggestions]

You may wish to do a regular suggestion first. It seems that the more bacteria being selected, the finer the suggestions are.

The suggestions are on a subdomain to distribute the load.

Clicking on a food shows the nutrients. Nutrient that are higher than typical have a * . These are the reason for the food being selected. One or more of these nutrients should help your microbiome.

Walkthru of Updated Suggestions — with CONSENSUS

See this post for background of the sample used.