Beyond simple naïve microbiome analysis?

Foreword

This post started out with a title of “Post-Acute COVID-19 Syndrome vs Myalgic Encephalomyelitis – Similarities and Differences“. It scope was pretty obvious — compare microbiome shifts from these two sibling conditions. Expectations was a bland informational review.

The result was calling into question the typical assumption that we could isolate symptoms and conditions to specific bacteria. I follow the statistics and discovered that you can get a magnitude better statistical significance by moving beyond bacteria. In coming weeks, I hope to code up suggestions AI based on this enlightenment.

My starting point

In my last post, Long COVID – an update, I did a comparison between the citizen science data and the literature published on the US Library of Medicine. In terms of symptoms, these two appear the same — but at the microbiome (and enzyme levels) how similar are they?

  • Post-Acute COVID-19 Syndrome (PCAS), also known as Long COVID
  • Myalgic Encephalomyelitis (ME), also known as Chronic Fatigue Syndrome (CFS)

One frustrating aspect of many studies on the US Library of Medicine for many conditions is simple: results are not replicated in subsequent studies for the same condition. Historically I have viewed this as a result of different equipment and different reference libraries. In many cases the bacteria deemed significant are often different and when they did report the same bacteria, they report opposite shifts!

This post explores some of these issues, and came to an interesting conclusion.

Study Caveats

The studies on the US Library of Medicine compare people with the condition to healthy controls. With the citizen science data that is almost impossible to do. If a person has gotten a microbiome test, they likely have some condition(s) and thus are not healthy controls!!

This is not all bad. It means that when we find things that are statistically significant they are differentiators against other people with microbiome issues. That is, how are people with ME different than people with FM and IBS. Conceptually, we are more likely to identify the key features for these conditions and not key features for auto-immune conditions or a gut disturbance in general. It is a nuisance difference, but may be a very important nuisance.

Comparison that we will review are from:

  • US Pubmed — bacteria reported by both with direction
  • KEGG Enzymes shifts from Citizen Science (using only Biomesight data)
  • Bacteria shifts from Citizen Science (using only Biomesight data)
Citizen Science Samples
Studies on US National Library of Medicine

For citizen science we may have many uploaded samples annotated both with PCAS and ME. To resolve this conflict, ME will contain only samples with ME and without PCAS. Both ME and PCAS have many, many comorbid symptoms which may also come into play. Many of the pure ME samples are before COVID swept the world, hence relatively clean. PCAS are more recent samples.

For PACS citizen science data, we have only significance difference identified from Biomesight data, hence we will compare those only.

ScopeMEPACSSame
US National Library of Medicine6823325
Enzymes – Citizen Science with p < 0.00122819931
Bacteria – Citizen Science109360
Entities reported as significant or found significant

I must admit that finding no bacteria in common with the same lab and the same reference library was a little bit of a surprise. One explanation is that microbiome dysfunctions evolve over time. People with PACS have had it less then 3 years, likely an average of just 1 year. People with ME has had it often for 30+ years. Comparing the two may be similar to comparing a one bottle of grape juice to a bottle of vintage wine.

Details for Common Bacteria from US National Library of Medicine

In the table below: H indicates High, L indicates Low.

Note that Bacteroides are reported high and low in different studies, suggesting there are subsets of each condition

tax_ranktax_NameDirection
classBacteroidiaH
familyBacteroidaceaeH
familyClostridiaceaeH
familyLachnospiraceaeL
genusAnaerostipesL
genusBacteroidesH
genusBacteroidesL
genusBifidobacteriumL
genusCoprobacillusH
genusCoprococcusL
genusDoreaL
genusEggerthellaH
genusEnterococcusH
genusFaecalibacteriumL
genusLactobacillusL
genusStreptococcusH
genusTuricibacterH
orderEubacterialesL
phylumBacteroidetesH
phylumFirmicutesL
phylumFusobacteriaH
speciesAnaerobutyricum halliiL
speciesEnterocloster bolteaeH
speciesFaecalibacterium prausnitziiL
speciesRuminococcus gnavusH
From https://microbiomeprescription.com/Library/PubMed

Details for Shared Enzymes with p < 0.001

In recent posts for conditions comorbid with ME, PACS, I found that enzyme analysis had greater statistical significance than bacteria. All of these posts reported higher enzyme levels were significant with these conditions.

The result for items shared that had p < 0.001 was almost overwhelming!

ECKeyEnzymeName
1.1.1.2921,5-anhydro-D-mannitol:NADP+ oxidoreductase
1.12.98.4H2:polysulfide oxidoreductase
1.7.2.2ammonia:ferricytochrome-c oxidoreductase
1.8.7.3CoB,CoM:ferredoxin oxidoreductase
1.8.98.4CoB,CoM,ferredoxin:coenzyme F420 oxidoreductase
1.8.98.5CoB,CoM,ferredoxin:H2 oxidoreductase
1.8.98.6coenzyme B,coenzyme M,ferredoxin:formate oxidoreductase
2.3.1.201acetyl-CoA:UDP-2-acetamido-3-amino-2,3-dideoxy-alpha-D-glucuronate N-acetyltransferase
2.7.1.2271-phosphatidyl-1D-myo-inositol:a very-long-chain (2’R)-2′-hydroxy-phytoceramide phosphoinositoltransferase
2.7.8.12CDP-glycerol:4-O-[(2R)-glycerophospho]-N-acetyl-beta-D-mannosaminyl-(1->4)-N-acetyl-alpha-D-glucosaminyl-diphospho-ditrans,octacis-undecaprenol glycerophosphotransferase
2.7.8.36UDP-N,N’-diacetylbacillosamine:tritrans,heptacis-undecaprenyl-phosphate N,N’-diacetylbacillosamine transferase
3.1.1.114methyl acetate acetohydrolase
3.1.3.27phosphatidylglycerophosphate phosphohydrolase
3.1.6.6choline-sulfate sulfohydrolase
3.1.6.8cerebroside-3-sulfate 3-sulfohydrolase
3.10.1.1N-sulfo-D-glucosamine sulfohydrolase
3.2.1.116-alpha-D-glucan 6-glucanohydrolase
3.2.1.152mannosylglycoprotein endo-beta-mannosidase
3.2.1.197beta-1,2-D-mannoside mannohydrolase
3.2.1.24alpha-D-mannoside mannohydrolase
3.4.21.26prolyl oligopeptidase
4.1.99.1L-tryptophan indole-lyase (deaminating; pyruvate-forming)
4.2.2.20chondroitin-sulfate-ABC endolyase
4.2.2.21chondroitin-sulfate-ABC exolyase
4.2.2.3alginate beta-D-mannuronate—uronate lyase
4.2.2.8heparin-sulfate lyase
4.3.1.7ethanolamine ammonia-lyase (acetaldehyde-forming)
5.1.1.20L-alanyl-D-glutamate epimerase
5.1.3.11cellobiose 2-epimerase
5.3.1.22hydroxypyruvate aldose-ketose-isomerase
6.1.1.13D-alanine:poly(phosphoribitol) ligase (AMP-forming)

One of them caught my eye, heparin-sulfate lyase, because micro-clots and “thick blood” are associated with these conditions with good results reported from the use of heparin for some patients.

 HSGAGs are widely distributed on the cell surface and extracellular cell matrix of virtually every mammalian cell type and play critical role in regulating numerous functions of blood vessel wall, blood coagulation, inflammation response and cell differentiation.

Microbial heparin/heparan sulphate lyases: potential and applications [2012]

Bacteria – Citizen Science

This blew me away — we have over 150 people with PCAS and over 250 with ME giving us superior sample sizes. We have 145 bacteria deemed significant for one or the other. We had NONE that was in common. This gut punch gives two main options: denial and look for an excuse to disregard. or roll with the punch and roll with enzymes.

Bottom Line

The enzyme aspect is the strongest association between PACS and ME. The count is higher, but more important, we are dealing with p < 0.001 data making false positives unlikely. This leads to a model that there is no ‘magical list of bacteria involved’ but a diverse array of bacteria that may be different for each person — but united in the over production of enzymes. This shifts the microscope of research into a different light spectrum. This is very interesting and may require some new brain cells to be used.

Using this information to improve..

If Enzymes estimate trumps bacteria levels (in a statistical sense), then we need to look at the enzyme levels and deduce for each one of concern, which collection of bacteria needs reduction — even when they are in the normal range. It is the aggregation of bacteria where the issue arises, not individual bacteria or specific subsets of bacteria.

A few examples may illustrate things a little

Example: (S)-3-hydroxy-3-methylglutaryl-CoA acetoacetate-lyase (acetyl-CoA-forming) a.k.a. EC 4.1.3.4, which was the most significant for PACS in the post: Long COVID – an update. There are some 2000+ taxon associated with it. We look at the averages for these below.

RankTax_NameWith PACSWithout PACSTScoreDF
speciesFaecalibacterium prausnitzii1381511096043.796775667
speciesPseudomonas viridiflava53252.62810832
speciesComamonas kerstersii125402.60038854
speciesPseudomonas aeruginosa62311.82464443
speciesEmticicia oligotrophica23039671.727619455
speciesDenitratisoma oestradiolicum42241.65065722
speciesGranulicella tundricola29211.6122548
speciesBacillus subtilis40191.37443117
speciesNiabella soli31240.96394316
speciesRalstonia insidiosa53380.91487436
speciesOligella ureolytica51320.8976819
speciesGlaciecola nitratireducens27240.6789966
speciesBacillus halotolerans32280.37121958
speciesAcidaminococcus intestini7496240.357674146
speciesAcinetobacter guillouiae67630.09895618
Key Contributors to EC 4.1.3.4,

For another one, we see the pattern stronger. Below we see the difference of Faecalibacterium prausnitzii is around 30,000 units. Looking at the other contributors, we see an additional 40,000 units. These extra units doubles the shift (and thus significance) of the enzyme above that of a single bacteria. Some of these are deemed healthy usually, for example: Akkermansia muciniphila which was at the 78%ile for Without PACS and 83%ile with PCAS. Neither would be deem to be outliers.

RankTaxon NameWith
PACS
Without
PACS
t-scoreDF
speciesFaecalibacterium prausnitzii1381511096043.796775667
speciesSutterella wadsworthensis962667722.380718452
speciesAliarcobacter skirrowii3756212.22360217
speciesAkkermansia muciniphila19096122901.896922547
speciesDesulfovibrio desulfuricans14234691.76977232
speciesEmticicia oligotrophica23039671.727619455
speciesEnterococcus casseliflavus1965811.63566638
speciesPorphyromonas asaccharolytica13502541.59988186
speciesBacteroides fragilis808055951.523991489
speciesBifidobacterium dentium14544611.433823239
speciesPhocaeicola dorei35482290751.396731649
speciesCorynebacterium aurimucosum11054071.27523496
speciesBacteroides eggerthii14379103451.108857263
speciesCorynebacterium jeikeium18977230.85828270
speciesPhocaeicola coprophilus649636420.856783152
speciesDesulfovibrio piger203215340.848976141
speciesMegamonas funiformis167711300.62028390
speciesHathewaya histolytica289027290.467066660
speciesHaemophilus parainfluenzae134312500.282656500
speciesMesoplasma entomophilum118210690.230055294
speciesPhocaeicola vulgatus51403512130.034398665
Key Contributors for EC6.1.1.6

Going Forward

The logical approach is simple to describe. For a person with the symptom, determine the enzymes which are abnormal. Determine the bacteria that are too high (even if only a little). Then use the suggestions AI Engine to determine the substances that will affect the greatest number of these bacteria to shift in the desired direction without encouraging other bacteria that could contribute to these enzymes to increase.

Now, the mathematics and complexities of this computation is a different matter but well within the power of today’s computer.

German CFS Patient got COVID….

This request came from the person discussed in Follow up to: A German CFS Patient Experience and Analysis.

I don’t know, if you remember me, we did two reports together, and your suggestions really helped to get my microbiome back on track (which shows in the samples).

And then I got COVID in November 2021-December 2021. But I felt better with it, but unfortunately I couldn’t give up my sample while having COVID.

Anyway I wanted to ask you whether you may be interested in my case, because I had a huge, irreversible it seems, crash from 20-30 on Bell CFIDS disability scale to now under 10 and my microbiome crashed along with me . (The crash also resulted in a high number of Lorazepam intake from which I’m slowly withdrawing now. But I didn’t get a clear idea of the effect of Lorazepam on the microbiome, other then they make the slowed gut motility worse of course.)

I have a very severe and have a progressive form of ME/CFS in the way that whenever I really crash I always go down to a lower baseline and do not recover. And with most crashes I loose about 50 % of my functionality, so it just took me one year to go from very mild to very severe.

From my lowest point onwards I’ve always had to take about 4 Lorazepam to guarantee a minimum of a bearable quality of life in bed. I succeeded for 4 years not to have a major crash and did did not build up a tolerance towards Lorazepam in that time.

A lot of things seem to have reversed, what I should take before are often things that I now should avoid. What Biomesight says seems to contradict slightly from what I can gather from your site. (Yes, I know you explained why there can be contradictory results).

And I have difficulties getting the suggestions for the handpicked criteria to show. Of course I would be super glad, if you could help, but I understand if you have more interesting projects to work on. (I would of course donate for your effort, as this is the only or easiest way to say thank you),

I believe one of the differences between Microbiome Prescription(MP) and Biomesight is simply the number of studies used to make suggestions. At present, we have over 11,000 studies coded into MP, I do not know the number that Biomesight uses, but I expect less than 1%. Also, MP suggestions was written by a person that has worked professionally in Artificial Intelligence. I suspect Biomesight lacks that skill set for development. Regardless, put items not in disagreement as first priority.

Analysis — The Numbers

There is no magic number that answers questions about the microbiome. Usually, I look for abnormalities. Since the earlier post, she had 6 more microbiome samples done periodically and shown below. She is wise to regularly monitor and ideally take moderate steps (diet and supplements) to counter any concerning trends.

CriteriaSep21Mar22May22Sep22Jan23May23
Shannon Diversity Index78.294.367.153.998.984.70
Simpson Diversity Index30.740.744.417.542.948.90
Chao1 Index53.666.881.536.765.161.90
Lab Read Quality4.87.37.75.256.5
Bacteria Reported By Lab612653717536636642
Bacteria Over 99%ile2159684
Bacteria Over 95%ile42050333212
Bacteria Over 90%ile294469506838
Bacteria Under 10%ile44181181405343
Bacteria Under 5%ile1216416592014
Bacteria Under 1%ile1140148130
Rarely Seen 1%537022
Rarely Seen 5%161121101915
Pathogens282938313234
Outside Range from JasonH556688
Outside Range from Medivere121219191919
Outside Range from Metagenomics99101066
Outside Range from MyBioma666699
Outside Range from Nirvana/CosmosId202014142121
Outside Range from XenoGene363636363939
Outside Lab Range (+/- 1.96SD)2122416189
Outside Box-Plot-Whiskers67831069410658
Outside Kaltoft-Moldrup641832188710675
Condition Est. Over 99%ile000000
Condition Est. Over 95%ile020000
Condition Est. Over 90%ile035000
Enzymes Over 99%ile0021000
Enzymes Over 95%ile19066151736
Enzymes Over 90%ile68131193427118
Enzymes Under 10%ile302852039420080
Enzymes Under 5%ile13225130418127
Enzymes Under 1%ile1164802211
Compounds Over 99%ile1017000
Compounds Over 95%ile1803531018
Compounds Over 90%ile49573131764
Compounds Under 10%ile78987696511241135998
Compounds Under 5%ile77984892710921057959
Compounds Under 1%ile77383290410691018930
Sep21Sep21Mar22Mar22May22May22Sep22Sep22Jan23Jan23May23May23
PercentileGenus%Genus%Genus%Genus%Genus%Genus%
0 – 974%4626%4323%75%116%96%
10-191911%137%95%1712%2715%2113%
20 – 292615%148%158%1611%148%2314%
30 – 39138%137%168%128%159%1811%
40 – 49148%137%147%1712%1810%159%
50 – 59148%169%147%107%159%1610%
60 – 692213%2011%189%107%1710%1811%
70 – 792313%158%2212%1913%169%138%
80 – 892313%1911%189%1812%2112%159%
90 – 99116%116%2212%1913%2112%138%
Total172180191145175161
Sep21Sep21Mar22Mar22May22May22Sep22Sep22Jan23Jan23May23May23
Percentile%Species%Species%Species%Species%Species%Species
0 – 95%1028%6027%707%1410%228%16
10-1913%265%115%1312%2315%3316%34
20 – 2913%278%186%169%1810%2312%25
30 – 397%154%86%1512%2310%2211%23
40 – 499%198%169%248%158%1810%21
50 – 5912%259%2012%309%1810%2212%25
60 – 698%1712%258%217%148%176%12
70 – 7910%209%197%1911%229%2010%21
80 – 8913%279%197%1916%309%219%19
90 – 997%158%1712%308%1512%287%15
201213257192226211

We lack any data on Lorazepam and other Benzodiazepines impacts on the microbiome which complicates interpretations. I did a search on the US National Library of Medicine and found nothing useful.

More History of Patient

I discovered Pregabalin in March 22 which brought me from Bell CFIDS disability scale below 10 up to nearly bell 20-30. The ditch in the curve around May 22nd is probably me taking too much Lorazepam and Pregabalin, as I for the first time I could take care of things that needed to betaken care of.

At that time I took about 500mg metformin (which did give me energy) most of the day and stayed with my Thorne Fibre mend, Inulin (in the beginning Inulin from the Argave helped dramatically with nausea and headaches)and Acacia Fibre, sometime an Amino Acid complex, but they make me jittery. Usually completely constipated I suddenly developed a strong diarrhea along with an unbearable itching of my whole skin in August / September for which Famotidine(Pepcid) and Cromoglicic acid (Cromolyn – prescription in US) worked best. That was a time where I ate lots of cake and carbohydrates and would take Metformin (I am always hovering around the entrance point to prediabetic) afterwards. That seemed to be too much sugar, my body couldn’t deal with. After I stopped the cake , eat more vegetables again, it went away. 

I have got restless legs, which are kind of turned on or off with every mayor crash. Now unfortunately they are turned on, and the only thing apart from medication that helps is when I eat complex carbohydrates lie brown rice, whole food, pasta, oat flakes etc, when I don’t I use Pramipexole.

Pregabalin been used with Fibromyalgia, a sibling condition for some, and suggested by the American Family Physician journal in 2023. Pregabalin with Lorazepam has known interactions: ” increase side effects such as dizziness, drowsiness, confusion, and difficulty concentrating.”[Src] so she is right about her loss of effectiveness.

Of the many items cited, we know what a few of them likely shifts. Others we lack data.

This missing data illustrates the challenge of trying to manipulate the microbiome — an absence of data. For antibiotics we have a reasonable amount of information, thus we can negotiate with MDs between their desired goal for the antibiotic and our goal of improving the microbiome to find a mutually acceptable compromise.

Going Forward

As part of my learning process, I evaluated each against the “Just Give Me Suggestions” consensus to see it that provide any insight. I also looked at the top items in three other classes.

CriteriaSep21Mar22May22Sep22Jan23May23
cromolyn disodium salt275.5243.9368.9504.3391.1393.3
famotidine275.5248.8378.5504.3379.7393.3
metformin146.4163.8234.1249.9293-17
inulin-231.6-79.1-207.5-203.3-333-157
Total399587725806631491
Best Probioticlactobacillus caseilactobacillus caseilactobacillus caseilactobacillus caseilactobacillus caseilactobacillus casei
Best Amino Acidpolymannuronic acidpolymannuronic acidmelatonin supplementmelatonin supplementmelatonin supplementpolymannuronic acid
Best Vitamin/MineralVitamin B7Vitamin CVitamin CVitamin B1Vitamin B1Vitamin B-12
Great Consistency across the samples!

This helps us evaluate possible (we do not know for certain) impact on various microbiome.

I am not a medical professional and have no clinical experience, so picking items tend to be arbitrary in most cases. I am familiar with the literature for ME/CFS and if the person has ME/CFS, I will tend to pick items that studies reporting helping.

My preference is simple.

My suggestion (given all of the fuzziness and items being taken) is to persist with the prescription items — they help both her symptoms and her microbiome! I would suggest adding the following items (see Dosages for Supplements for literature on dosage):

  • lactobacillus casei – at least 48 BCFU/day — this is the suggested serving size from Custom Probiotics product. Or a Yakult bottle with each meal (each bottle is 20 BCFU). Depending on availability and cost.
  • melatonin – 10 mg/d – in three dosages, i.e. one with each meal.
  • Vitamin B1, B12, C7 and C. (see above for dosages)

One additional item that I would suggest, being prediabetic is to take the Pendulum Akkermansia muciniphila probiotic. This may be a challenge to obtain in Germany (if someone is visiting the US, that may be a backdoor to get 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 can compute items to take, those computations do not provide information on rotations 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.

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.

The Transcribed Tests – a New Option: Condition Matching

As a result of doing an analysis for a 19 month old toddler, I added a new option that can also be used with Transcribed tests. This post applied to the following tests:

You must save your input.

Process

Here’s an example

When you logged in, you will see your saved tests, CLICK ON Review.

And then we have the details you entered below with an important column, taxon number.

Below this are conditions where your pattern matches at least 5 shifts reported in Published Studies.

There may be many items listed. This is by pattern matching and is not predictive.

If you have any of these conditions, or suspect you may have. Just click the appropriate button.

An example is below. These are tuned safest-suggestions for the matches. What do I mean by safest? It means the items are not reported in any study in the database to adversely impact any of bacteria listed. Many substances have contradictory reports on shifts — this substances are excluded.

Not Listed Condition?

This person believes they may have Autoimmune, so going to https://microbiomeprescription.com/Library/PubMed we find that it is listed.

If it is not listed, search for bacteria shifts reported and use those (please send me the studies so I may add them).

The bacteria are shown in a tree. You have to manually match between the two.

In this we have:

  • Escherichia     ⬇️  but our sample is high,
  • Roseburia intestinalis   ⬆️  - we are high on Roseburia, we will include it

We have only one match — this tests with limited reporting is not a good fit for this condition. Doing a test like Biomesight, Xenogene, Thorne or Ombre is likely the best choice.

We just copy the taxon number into the form at the bottom of the page, and then click suggestions.

In this case, we get a short list. Remember, doing a single bacteria means you are ignoring a lot of interactions and factors. The suggestions could feed other bacteria that are too high.


19 month old Toddler with GI-Issues

Backstory

A sample result dated 29/10/2023 it’s for 19month old son born via C section and having lots of ongoing tummy pain since birth.

Fully breastfed for well over 12 months but the microbiome doesn’t appear that way.

Analysis

This is a very much “flying by the seats of my pants” analysis. Why? From birth for the next 10-20 years the microbiome has dramatic natural changes. The Fuzzy Logic Expert System on Microbiome Prescription is tuned for adults and not these age ranges. If you are dealing with a child, the approach below is suggested.

I am going to use ChatGPT selectively to make analysis easier, checking that it’s answers agree with my memories from reading studies..

So, first some literature to frame this analysis in. There are 400+ studies on C Sections and Infant microbiome.

  • “There is certainly a transient difference in the gut microbiota of infants born by Cesarean delivery compared to their VD counterparts. While this difference appears to be corrected after weaning, it may have lifelong impacts on the development of the immune system. ” [2018]
  • “When comparing the gut microbiota composition of CSD babies with vaginally delivered (VD) babies, the former show a microbiome that closely resembles that found in the environment and the mother’s skin, while VD babies show a microbiome more similar to the vaginal microbiome. Although these alterations of normal gut microbiota establishment tend to disappear during the first months of life, they still affect host health in the mid–long term since CSD has been correlated with a higher risk of early life infections and non-transmissible diseases, such as inflammatory diseases, allergies, and metabolic diseases.” [2021]
    • Too late, but important for any future babies “Lab analysis showed that the microbiota of the C-section babies swabbed with their mother’s vaginal fluids was close to that of vaginally born babies” [2021]

Bifidobacteria and Firmicutes Dominance: In healthy infants and toddlers, the gut microbiome often shows dominance of beneficial bacteria like Bifidobacteria and Firmicutes. These bacteria play crucial roles in digestion, immune system development, and protection against pathogens.

Generally, Bifidobacterium can comprise anywhere from 10% to 40% or more of the total gut microbial population in toddlers.

In healthy toddlers, Firmicutes can typically constitute a substantial portion of the gut microbiota, often ranging from around 30% to 60% or more of the total bacterial population

From ChatGpt

Looking at Bifidobacterium, the numbers are lower (57%ile) than expected for a child of this age but with a rich diversity of species. Bifidobacterium is 2.4%, well below the expected 10-40%. Bacillota (formerly known as Firmicutes at 83%ile) is 79.4%, well above expected 30-60%.

Switch to consequence, ChatGpt reports:
“Some of the health implications of low Bifidobacterium levels in toddlers may include:

  1. Digestive Issues: Bifidobacterium species contribute to the breakdown of complex carbohydrates, aiding in the digestion of certain fibers and sugars. Low levels of these bacteria may result in digestive problems such as constipation, diarrhea, or irregular bowel movements.
  2. Weakened Immune Function: Bifidobacterium species are involved in regulating and supporting the immune system. Insufficient levels of these beneficial bacteria may compromise the immune response, making toddlers more susceptible to infections and illnesses.
  3. Increased Risk of Allergies and Asthma: Some research suggests that alterations in the gut microbiota, including low levels of Bifidobacterium, might be associated with a higher risk of developing allergies and asthma in children.
  4. Potential Weight and Metabolic Effects: The gut microbiome, including Bifidobacterium, can influence metabolism and energy regulation. Low levels of these beneficial bacteria in toddlers’ gut microbiota might potentially be linked to metabolic issues or an increased risk of obesity later in life, although this connection is still an area of ongoing research.
  5. Impact on Neurodevelopment: Emerging studies suggest a possible link between the gut microbiota and brain development. Some evidence indicates that alterations in gut bacteria, including Bifidobacterium, might influence cognitive development and behavior in children.
  6. Susceptibility to Infections and Antibiotics: A decrease in beneficial bacteria like Bifidobacterium can leave the gut more vulnerable to colonization by harmful bacteria. Moreover, toddlers with low levels of these beneficial bacteria may face a higher risk of complications after antibiotic treatments, as antibiotics can further disrupt the delicate balance of the gut microbiota.
  7. Digestive Imbalances: In some cases, an overabundance of certain Firmicutes strains might affect the balance of gut microbiota and contribute to digestive problems, including irregular bowel movements, bloating, or discomfort.”

At this point, using the Fuzzy-Logic Expert System on Microbiome Prescription is not a good choice to get suggestions. It is tuned for adults and not toddlers. All of the values are in the normal range for an adult, but definitely out of range for a toddler.

What we want is to increase one bacteria and decrease another bacteria without looking at the percentile. I just added a subsection on the Research Features tab to make that available. It requires the the taxon numbers be entered. In this case: Decrease: 1239, Increase 1678 (Bifidobacterium).

See this video for a walk thru of the process.

This results in this page

You can click on each modifier to verify that it only impacts the bacteria named by taxon in the desired way.

In toddlers, several Bifidobacterium species are commonly found in their gastrointestinal tract. Among these species, Bifidobacterium longum, Bifidobacterium breve, and Bifidobacterium infantis are frequently observed in the gut microbiota of toddlers. These species play essential roles in maintaining gut health, aiding in digestion, and supporting the immune system during early childhood.

ChatGPT

We can take this one step further, picking specific children :

With a deeper set of suggestions:

Feed Back

I usually send drafts to the person for comments, concerns etc. This was the response:

I wondered whether prevotella/segatella buccae was a concern as it was the highest species in the sample and bacteroides was extremely low. The practitioner we saw prescribed HMO and lactulose after reviewing Biomesight raw data.

Mother of child

The HMO suggestion is reasonable if you do not check all of the literature. We have contradictory results from studies for HMO. Remember Bacillota is the modern name for Firmicutes.

Similarly, we have some contradiction in results with Bifidobacterium — so it was not deemed ultra safe.

This suggests adding segatella buccae (NCBI 28126) be added.

The results are similar, with less items on the to avoid.

Trying a different combinations, for example

We get different ordering and a few changes.

Bottom Line

We have various sets of suggestions, doing a consensus is likely the best path forward.

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 information on rotations 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.

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.Posted on  b

Chronic Lyme Microbiome Analysis

Back Story Section

April 2022 strong antibiotic treatment against another pathogen flared my chronic borrelia/babesia/bartonella. [I had Ceftriaxone iv and 1500mg of azithromycin as a single dose].

Shortly after this stinging started in the belly and burning when passing a stool and urinating. Its yeast symptoms. I have mthfr mutation and low bifido bacteria.

“chronic borrelia/babesia/bartonella” is also known as Chronic Lyme disease. See Lyme Disease Co-Infections | LymeDisease.org. It is a close sibling to ME/CFS, Long COVID and Occult Rickettsia. There are 77 samples uploaded marked with Lyme, 45 of these also indicate ME/CFS (58% overlap). There was no statistically significance difference in the microbiome between these two groups.

This person requested a video walkthrough due to cognitive issues with reading.

Analysis

Looking at the Percentile-Percentage distribution, we see the common pattern with ME/CFS and Long COVID: over representation of the 0-9%ile range. The numbers in each percentile range should be about the same. They are not.

Looking at the new Anti inflammatory Bacteria Score [Score: 12.56 or 16.9 %ile], we see that bacteria controlling inflammation appears to be very deficient. Dr. Jason Hawrelak Recommendations is at 89%ile with the following anti-inflammation bacteria being flagged as low: Roseburia, Bifidobacterium, Lactobacillus and Akkermansia.

Looking at the Potential Condition lists, we see many that we would expect to see

  • Allergic Rhinitis (Hay Fever) 100%ile
  • Hyperlipidemia (High Blood Fats) 97%ile
  • Chronic Fatigue Syndrome 96%ile
  • Allergies 95%ile
  • Irritable Bowel Syndrome 94%ile
  • Functional constipation / chronic idiopathic constipation 93%ile

Going Forward

I checked the KEGG suggested probiotics none of the suggestions were strong. On the other hand we have a good number of supplement suggestions from KEGG (shown below). The higher the Z-Score, the more important they are.

Looking at probiotics we see the best ones being bifidobacterium (which is good because many lactobacillus produce d-lactic acid that causes brain fog).

  • bifidobacterium pseudocatenulatum,
  • bifidobacterium infantis,
  • bifidobacterium breve

There are some lactobacillus also suggested:

  • lactobacillus casei — documented to be good for allergies and hay fever. Usually I suggest Yakult, one vial around each meal.
  • lactobacillus reuteri — biogaia (reported not to produce d-lactic acid)

For supplements, checking the items from the KEGG list above, we found that all items suggested which we have data on, agreement that they should help:

  • N-Acetyl Cysteine (NAC), +185
  • l-proline + 161
  • l-glutamine + 76
  • l-arginine +45
  • l-phenylalanine +40

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 information on rotations 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.

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.

Bad Diet and Antibiotics? ME/CFS like symptoms

Back Story

  • 38yr Old now, Issues started around the age of 24-27 i think [gradual onset]
  • From the age of 17-35 my diet has been really bad ( Coca cola, pizza, burger, fries, candy and sweets etc)
  • From 23-25 I started getting really tired everyday followed by pains in various locations
  • Later, started loosing weight in the face, eyes started to sink deeper and deeper, my face become really gaunt. All my life i have been thin and could never gain weight nomatter how much i ate.
  • I also startet getting extremly fatigue after eating.
  • definitive stomach issues started around the age of 30-33, may have been before.
  • Since I turned 34, i have been trying to figure out what is wrong with me.
    • Allof the standard checks at the docs Office(ultrasound of organs and stomach area, CT/MRI of stomach area, Colonscophy and gastroscophy)
    • Nothing found

So everything points towards gut dysbiosis or something like that

I started to change around with my diet July 2022. Details of various attempted changes (Gluten free, no dairy, no sugar, carnivore diet) — currently on Keto with resistant carbs.

But many symptoms are still there.

I have been taken multiple rounds of antibiotics from november 2022 until Jan. 2023 (80 days) because i had a sinus and deviated septum surgery. I have also taken 7 days of metrodinazole  and amoxicilin 12 weeks ago because of the H Pylori infection i had. Retest was negative for H. Pylori
Got diagnosed with methane SIBO via breath test in september 2023

I have been diagnosed by a GI Map test in May 2023 with:

  • candida
  • E coli overgrowth
  • Streptococcus overgrowth
    by a gimap test in May 2023

I feel like my body is destroying itself.
A long list of symptoms was given

Analysis

Potential Medical Conditions Detected

Nothing stood out. By this I mean that the Percentile ranking is well into the Prevalence. The closest was SIBO where the borderline would be 100-52= 58%ile. He was reasonably over that. He wrote “Got diagnosed with methane SIBO via breath test in September 2023”, so this was a definite matching forecast from PubMed literature.

Bacteria deemed Unhealthy

The one item of interest was Faecalibacterium prausnitzii, which was 19% of his microbiome and associated with increased Candida risk (which he has had).

Dr. Jason Hawrelak Recommendations

Percentages of Percentiles

This is my quick way to statistically determine if there is statistically significant dysfunction. The significance is 0.99999.. etc, so yes.

Forecast Symptoms

In the top ones we had the following agreements with reality:

  • cold extremities
  • Rapid muscular fatigability
  • Joint pain
  • Sinus issues with headaches 
  • Onset: Gradual 
  • Sinus issue
  • Onset: 2010-2020 
  • Gender: Male
  • General: Headaches
  • Post-exertional malaise

The ones that did not match were connected to cognitive issues.

Pattern appear to match a subset of myalgic encephalomyelitis/chronic fatigue syndrome. Many MDs will suspect it, but will not give a diagnosis if the person is not totally disabled. The reason is simple, no treatment plan and likely a negative psychological impact.

Going Forward

This looks likes a good candidate for a two stage building a consensis:

  • “Just Give Me Suggestions”
  • THEN using special studies (everything at once – skipping Gender) to add a fifth set of suggestions

The suggestions are short and tight. Barley porridge with Walnuts for breakfast for most days.

I would suggest taking Danish product Biogaia Lactobacillus Reuteri just before bed each night for two weeks, then switch to clostridium butyricum for two weeks. The other probiotics – do 1 at a time for 1-2 weeks, take them 1-2 hours after breakfast.

Akkermansia Muciniphila probiotics and Swedish Filmjölk (on your porridge?) are two probiotics with no known negative impact and some positive impact. The list above are the highest predicted impact.

What to avoid

Keep up the no alcohol but reduce/drop beef in your carnivore diet. Go for herring, eels and other fish product. It is interesting that the two E.Coli probiotics are listed as avoid (the logic does not look at E.Coli levels, but other bacteria levels to make that suggestion)

Prescription Items (if you have a willing MD)

Doing antibiotics is usually consider if the above do not cause sufficiently improvement over time. I mentioned that the history looks quasi-ME/CFS. I was not surprise to see many ME/CFS antibiotics on the list, including:

  • AMOXICILLIN (ANTIBIOTIC)S[CFS]
  • AMPICILLIN (ANTIBIOTIC)S[CFS]
  • CIPROFLOXACIN (ANTIBIOTIC)S[CFS]

If you and your MD decide to try antibiotics, I would suggest on of those (using Dr. Jadin approach of pulsing).

Browsing the Details

High value was 701, low as -391. Usually these two numbers are about the same magnituded. Items spotted of note:

Note that inulin (prebiotic), jerusalem artichoke (prebiotic) etc are of low (but positive) value.

Questions

Q: Regarding your sugestion of all the probiotics. Usually the probiotic comes in bottles where there is like 4-10 different strains. Should i avoid that and only buy single strains in each bottle of all the ones you mentioned?

A: Each strain impacts things in different ways. My preference is always single strains, ideally ones that have been researched with the ideal being ones researched for your condition or symptoms and found effective. See https://microbiomeprescription.com/library/ProbioticSearch , There are reports of some probiotics making people worse. A major issue is that probiotics are not well regulated Many “retail mixtures” have over 60% of their contents misidentified. See Deceptive Probiotic Labels or Assessment of commercial probiotic bacterial contents and label accuracy, When the bottle gives an explicit strain (not species), then the owner of that strain has motivation to insure quality control.

Looking at the challenges of getting probiotics in Denmark. What may be an acceptable compromise is to find a probiotic mixture that does not contain any probiotics with an estimated adverse risk. In your case these are:

  • symbioflor 2 e.coli probiotics
  • colinfant e.coli probiotics
  • bacillus subtilis natto (probiotics)
  • bifidobacterium longum,lactobacillus helveticus (probiotics)
  • lactobacillus paracasei,lactobacillus acidophilus,bifidobacterium animalis (probiotics)
  • General Biotics Equilibrium
  • bifidobacterium (probiotics)
  • lactobacillus rhamnosus gg,lactobacillus,rhamnosus,propionibacterium
  • reudenreichii,bifidobacterium breve (probiotics)
  • bifidobacterium bifidum (probiotics)
  • bacillus licheniformis,(probiotics)
    Prescript Assist (2018 Formula)
  • lactobacillus bulgaricus (probiotics)
  • lactobacillus gasseri (probiotics)
  • lactobacillus rhamnosus (probiotics)
  • lactobacillus casei shirota (probiotics)
  • lactobacillus fermentum (probiotics)
  • lactobacillus sakei (probiotics)
  • lactobacillus delbrueckii bulgaricus,bifidobacterium bifidum,enterococcus faecium,candida pintolopesii,aspergillus oryzae (probiotics)
  • lactobacillus brevis (probiotics)
  • bifidobacterium adolescentis,(probiotics)
  • bifidobacterium lactis,streptococcus thermophilus probiotic

Example:  lactobacillus rhamnosus gg (probiotics) is an explicit strain (“GG”) is the second highest positive, while generic  lactobacillus rhamnosus is # 54 and negative.

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 information on rotations 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.

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.

Studies Quality Assurance Launch

Over the last two weeks, there has been a couple of email pointing out possible errors in some citations. I am not surprised. I expect 90-95% correctness (i.e. 1 in 10 or 1 in 20) may be incorrectly entered. To improve the quality, we need independent review of the data. In one amusing case, I quoted my source correctly but that review study incorrectly cited it’s source. The data entry was right, the source document was wrong.

The articles are technical studies which often require advance reading skills and knowledge of this topic. Some of the sources are available in full on the web for free, others are behind a paywall. If you are connected with a university or college, you may have access thru your institution.

If you cannot access the full text of the source, then skip it. Extracts and summaries can contain errors.

Process

Just email me from the email account that you logged in with and I will add auditor or QA permissions to your account.

Doing it

When you logged in, you should see:

When you look at citations, you will see the ⚖️ icon (or a ✅ if someone has already checked) beside the citation.

Example for a list of citations

Note that there may be more in the study then what the titles implies. Often data is from Appendix and tables.

Clicking ⚖️ will take you to a page showing what was extracted and gives you an opportunity to correct it,

Click [Report above Issue] will send emails to me and to your self. If all of the information is correct, then click [I have verified..] and the next time you see the citation, there will be a ✅ beside it. Your email is stored beside the citation as the reviewer.

You will get an email confirming stuff


If there is information that was missed (more likely) please include the TAXON numbers of the bacteria. This speeds up the process. Often information was missed because of alternative spelling.

That’s the process. Short, simple and with the ability for me to quickly make corrections.

Will Inulin have a good impact?

Response differences of gut microbiota in oligofructose and inulin are determined by the initial gut Bacteroides/Bifidobacterium ratios [2023] Indicates difference of response.

Bacteroides/Bifidobacterium (Ba/Bi) ratios “with Low Ratio showing a significant increase in propionic acid and being enriched in glycolysis functions, whereas High was enriched in amino acids and aminoglycolysis functions”

Of course, the question becomes what are low and high ratio? To answer that question, I pulled some data by lab

Ubiome Ratios

Ombre Ratios

BiomeSight Ratios

Bottom Line

I would suggest a ratio > 500 to 1000 is High, Below 200 is low

Bacteria Difference by Age, Gender, Blood Type

The following is based on Biomesight data uploaded with some annotated by uploaders. Technically, interpretation of microbiome results should factor these issues in. At least 10 samples had to have Symptom Name to be included. The numbers shown are averages (on count per million) on samples that reported the bacteria.

As a spot check, we see multiple Bifidobacterium in the 0-10 range which agrees with the literature.

In general, the symptom has more than the population because we filtered by using a high T Score to keep the list shorter for illustration purposes. A variety of other factors are not shown, for example: FUT2 non-secretor or FUT2 secretor.

Dropping the T-Score filtering to 1.96 resulted in 3600 rows.

Symptom NameNameRankPopulation
per million
Sample
per million
T-Score
Age: 0-10Listeriagenus323617.2
Age: 0-10Bifidobacterium magnumspecies2123016.4
Age: 0-10Bifidobacterium pseudocatenulatumspecies377091214.7
Age: 0-10Paenibacillusgenus373305.5
Age: 0-10Cystobacterineaesuborder191156.1
Age: 0-10Desulfovibrio vietnamensisspecies232264127
Age: 0-10Anaerostipesgenus1581217015.3
Age: 0-10Ethanoligenens harbinensespecies39157130.4
Age: 0-10Bifidobacterium bombispecies346747.3
Age: 0-10Eubacteriales incertae sedisnorank30090979.5
Age: 10-20Anaerococcus octaviusspecies10317387.2
Age: 10-20Bifidobacterium boumspecies34144120
Age: 10-20Puniceicoccalesorder8220917.2
Age: 10-20Bifidobacterium bombispecies34207223.1
Age: 10-20Eubacteriales incertae sedisnorank30091189.5
Age: 10-20Ruminiclostridiumgenus696103965.1
Age: 20-30Aggregatibacter aphrophilusspecies3544511.1
Age: 20-30Listeriagenus322675.2
Age: 20-30Bifidobacterium magnumspecies211207.8
Age: 20-30Halomonasgenus3082618.5
Age: 20-30Bifidobacterium pseudocatenulatumspecies37185455.3
Age: 20-30Halomonadaceaefamily404708.5
Age: 20-30Lactobacillus crispatusspecies356215838.1
Age: 20-30Fibrobacteresphylum2246602832.3
Age: 20-30Brenneriagenus53132110.7
Age: 20-30Dietziaceaefamily11316275.4
Age: 20-30Piscirickettsiaceaefamily241376.7
Age: 20-30Desulfovibrio vietnamensisspecies23162590.8
Age: 20-30Ethanoligenens harbinensespecies393085.3
Age: 20-30Saccharospirillaceaefamily18972110.2
Age: 20-30Prevotella maculosaspecies107298017.5
Age: 20-30Eubacteriales incertae sedisnorank30053405.4
Age: 20-30Eubacteriales Family XII. Incertae Sedisfamily3871511.2
Age: 20-30Pectobacteriaceaefamily53125710.7
Age: 20-30Balneolaeotaphylum2620413791.7
Age: 30-40Francisellagenus183459456.5
Age: 30-40Enterobacter cloacaespecies9813058.4
Age: 30-40Aggregatibacter aphrophilusspecies35124732.7
Age: 30-40Aggregatibacter segnisspecies8416009.4
Age: 30-40Halomonasgenus303818.2
Age: 30-40Bifidobacterium pseudocatenulatumspecies376838207
Age: 30-40Francisellaceaefamily183239427.3
Age: 30-40Halochromatium salexigensspecies231256
Age: 30-40Cystobacterineaesuborder191095.7
Age: 30-40Dietziaceaefamily11318566.2
Age: 30-40Halochromatiumgenus241879.4
Age: 30-40Desulfovibrio vietnamensisspecies233094174
Age: 30-40Ethanoligenens harbinensespecies393646.5
Age: 30-40Saccharospirillaceaefamily1856763.4
Age: 30-40Prevotella maculosaspecies1071239474.7
Age: 30-40Eubacteriales incertae sedisnorank30053055.4
Age: 30-40Eubacteriales Family XII. Incertae Sedisfamily383525.2
Age: 30-40Balneolaeotaphylum26223685.8
Age: 30-40Rhodovibrionaceaefamily119402222.4
Age: 40-50Aggregatibacter aphrophilusspecies3577119.9
Age: 40-50Bifidobacterium pseudocatenulatumspecies374210127
Age: 40-50Francisellaceaefamily1862680.7
Age: 40-50Fibrobacteresphylum2242933014.3
Age: 40-50Cystobacterineaesuborder191387.6
Age: 40-50Desulfovibrio vietnamensisspecies233100174.3
Age: 40-50Ethanoligenens harbinensespecies3985716.3
Age: 40-50Saccharospirillaceaefamily1820922
Age: 40-50Prevotella pleuritidisspecies52220217.1
Age: 40-50Megamonas funiformisspecies1344337547.2
Age: 40-50Prevotella maculosaspecies107453526.9
Age: 40-50Eubacteriales Family XII. Incertae Sedisfamily3885813.6
Age: 40-50Balneolaeotaphylum2612551486.4
Age: 40-50Rhodovibrionaceaefamily11912496.5
Age: 50-60Desulfomicrobiumgenus342768.3
Age: 50-60Bifidobacterium pseudocatenulatumspecies377205218.1
Age: 50-60Hathewaya proteolyticaspecies19896.6
Age: 50-60Paenibacillusgenus373706.2
Age: 50-60Fibrobacteresphylum224175118.5
Age: 50-60Sporotomaculum hydroxybenzoicumspecies37230136.9
Age: 50-60Cystobacterineaesuborder1917810.2
Age: 50-60Olsenellagenus13142759.8
Age: 50-60Desulfovibrio vietnamensisspecies233624204
Age: 50-60Desulfomicrobiaceaefamily342788.4
Age: 50-60Ethanoligenens harbinensespecies39190737.1
Age: 50-60Saccharospirillaceaefamily1836540.1
Age: 50-60Tepidimicrobiumgenus271587
Age: 50-60Opitutaeclass17335325.3
Age: 50-60Puniceicoccalesorder82362712.8
Age: 50-60Eubacteriales incertae sedisnorank30057555.9
Age: 50-60Eubacteriales Family XII. Incertae Sedisfamily385418.3
Age: 50-60Clostridium amylolyticumspecies211318.4
Age: 50-60Atopobiaceaefamily11329457.2
Age: 50-60Balneolaeotaphylum265457210.9
Age: 60-70Achromobactergenus282466.7
Age: 60-70Salmonellagenus7418707.4
Age: 60-70Aggregatibacter aphrophilusspecies353819.3
Age: 60-70Desulfomicrobiumgenus342266.6
Age: 60-70Deinococcus-Thermusphylum83217212.4
Age: 60-70Lacticaseibacillus paracaseispecies1141074825.3
Age: 60-70Limosilactobacillus fermentumspecies632015978.5
Age: 60-70Bifidobacterium magnumspecies2130222.1
Age: 60-70Sphingomonasgenus49531737.2
Age: 60-70Bifidobacterium pseudocatenulatumspecies37387361177.7
Age: 60-70Deltaproteobacteriaclass5224402765
Age: 60-70Salmonella entericaspecies7414165.6
Age: 60-70Burkholderiagenus99414624
Age: 60-70Sphingomonadaceaefamily57461521
Age: 60-70Paenibacillusgenus373746.3
Age: 60-70Abiotrophia defectivaspecies356606.1
Age: 60-70Fibrobacteresphylum224209585102.7
Age: 60-70Sporotomaculum hydroxybenzoicumspecies37157125
Age: 60-70Bifidobacterium boumspecies346699
Age: 60-70Cystobacterineaesuborder191266.8
Age: 60-70Burkholderiaceaefamily27230985.4
Age: 60-70Turicibacter sanguinisspecies89509219.1
Age: 60-70Deinococciclass83217212.4
Age: 60-70Chloroflexiphylum11020618.6
Age: 60-70Desulfovibrio vietnamensisspecies232883162.1
Age: 60-70Sphingomonadalesorder58444620.8
Age: 60-70Desulfomicrobiaceaefamily342176.3
Age: 60-70Ethanoligenens harbinensespecies395199.5
Age: 60-70Saccharospirillaceaefamily1828030.2
Age: 60-70Acholeplasma equifetalespecies241147.8
Age: 60-70Prevotella pleuritidisspecies52240018.7
Age: 60-70Prevotella maculosaspecies107576134.4
Age: 60-70Bifidobacterium bombispecies34125213.8
Age: 60-70Synergistetesphylum3014899719.8
Age: 60-70Eubacteriales incertae sedisnorank30080638.3
Age: 60-70Eubacteriales Family XII. Incertae Sedisfamily385568.6
Age: 60-70Slackia piriformisspecies16630215.9
Age: 60-70Lactobacillus casei groupspecies group319107509.8
Age: 60-70Ruminiclostridiumgenus696162128.1
Age: 60-70Balneolaeotaphylum2611534446.9
Age: 60-70Limosilactobacillusgenus245143899.2
Age: 60-70Rhodovibrionaceaefamily119261614.3
Age: 70-80Eubacteriales incertae sedisnorank30070647.3
Age: 70-80Ruminiclostridiumgenus696111415.5
Blood Type: A NegativeButyrivibriogenus46760875.3
Blood Type: A PositiveAggregatibacter aphrophilusspecies35115030.1
Blood Type: A PositiveBifidobacterium pseudocatenulatumspecies3710314312.8
Blood Type: A PositiveHathewaya proteolyticaspecies19836
Blood Type: A PositiveLactobacillus crispatusspecies356182136.8
Blood Type: A PositiveFibrobacteresphylum2244128720.1
Blood Type: A PositiveDesulfovibrio vietnamensisspecies232546143
Blood Type: A PositiveEthanoligenens harbinensespecies393656.5
Blood Type: A PositiveSaccharospirillaceaefamily1829732.2
Blood Type: A PositivePrevotella pleuritidisspecies52378529.7
Blood Type: A PositivePrevotella maculosaspecies107822849.4
Blood Type: A PositiveEubacteriales incertae sedisnorank30071207.3
Blood Type: A PositiveEubacteriales Family XII. Incertae Sedisfamily3866610.4
Blood Type: A PositiveRuminiclostridiumgenus696103225
Blood Type: A PositiveRhodovibrionaceaefamily11912146.3
Blood Type: B PositiveEthanoligenens harbinensespecies39378274.4
Blood Type: B PositiveMoryellagenus15852546.4
Blood Type: FUT2 non-secretorEubacteriales incertae sedisnorank3001161112.2
Blood Type: O NegativeHalomonadaceaefamily40108820.8
Blood Type: O NegativeAlteromonadaceaefamily414885.4
Blood Type: O NegativeEthanoligenens harbinensespecies394508.2
Blood Type: O NegativeEubacteriales incertae sedisnorank30059096
Blood Type: O NegativeEubacteriales Family XII. Incertae Sedisfamily38246240.1
Blood Type: O NegativeSymbiobacteriaceaefamily11315365.3
Blood Type: O NegativeRuminiclostridiumgenus696153287.6
Blood Type: O NegativeMorganellaceaefamily685328746
Blood Type: O PositiveAchromobactergenus282276.1
Blood Type: O PositiveKlebsiella pneumoniaespecies11314317.1
Blood Type: O PositiveSalmonellagenus7413345.2
Blood Type: O PositiveAggregatibacter aphrophilusspecies353388.2
Blood Type: O PositiveDeinococcus-Thermusphylum8316139.1
Blood Type: O PositiveLacticaseibacillus paracaseispecies114820619.3
Blood Type: O PositiveLimosilactobacillus fermentumspecies631572961.2
Blood Type: O PositiveBifidobacterium magnumspecies2123216.6
Blood Type: O PositiveSphingomonasgenus49383126.7
Blood Type: O PositiveBifidobacterium pseudocatenulatumspecies37330841005.7
Blood Type: O PositiveBurkholderiagenus99258214.8
Blood Type: O PositiveFrancisellaceaefamily182597342.1
Blood Type: O PositiveSphingomonadaceaefamily57332615.1
Blood Type: O PositivePaenibacillusgenus373746.3
Blood Type: O PositiveFibrobacteresphylum22417055583.5
Blood Type: O PositiveSporotomaculum hydroxybenzoicumspecies37110517.4
Blood Type: O PositiveBifidobacterium boumspecies344546
Blood Type: O PositiveCystobacterineaesuborder191216.5
Blood Type: O PositiveTuricibacter sanguinisspecies89358313.3
Blood Type: O PositiveDeinococciclass8316139.1
Blood Type: O PositiveChloroflexiphylum11014666
Blood Type: O PositiveDesulfovibrio vietnamensisspecies232704151.9
Blood Type: O PositiveSphingomonadalesorder58306714.3
Blood Type: O PositiveEthanoligenens harbinensespecies39101119.3
Blood Type: O PositiveSaccharospirillaceaefamily1829131.5
Blood Type: O PositivePrevotella pleuritidisspecies52136310.4
Blood Type: O PositivePrevotella maculosaspecies1071250075.3
Blood Type: O PositiveBifidobacterium bombispecies34109012
Blood Type: O PositiveSynergistetesphylum3013487814
Blood Type: O PositiveEubacteriales incertae sedisnorank30072117.4
Blood Type: O PositiveEubacteriales Family XII. Incertae Sedisfamily385268.1
Blood Type: O PositiveSlackia piriformisspecies16627535.3
Blood Type: O PositiveLactobacillus casei groupspecies group319107519.8
Blood Type: O PositiveRuminiclostridiumgenus696115015.6
Blood Type: O PositiveBalneolaeotaphylum264614178.2
Blood Type: O PositiveLimosilactobacillusgenus245116187.4
Blood Type: O PositiveRhodovibrionaceaefamily11913467.1
Gender: FemaleFrancisellagenus181666218.6
Gender: FemaleSerratia marcescensspecies12414497.2
Gender: FemaleDesulfomicrobiumgenus341805
Gender: FemaleBifidobacterium magnumspecies2115710.7
Gender: FemaleCarnobacteriumgenus292506.3
Gender: FemaleBifidobacterium pseudocatenulatumspecies379394284.8
Gender: FemaleFrancisellaceaefamily181575206.6
Gender: FemaleFibrobacteresphylum2243498417
Gender: FemaleCystobacterineaesuborder191377.5
Gender: FemaleDietziaceaefamily11316875.6
Gender: FemalePlanomicrobiumgenus201067.3
Gender: FemaleDesulfovibrio vietnamensisspecies233181178.9
Gender: FemaleEthanoligenens harbinensespecies3984316
Gender: FemaleSaccharospirillaceaefamily1841045.3
Gender: FemalePrevotella pleuritidisspecies529006.7
Gender: FemaleMegamonas funiformisspecies1344244565.2
Gender: FemalePrevotella maculosaspecies107339820
Gender: FemaleEubacteriales incertae sedisnorank30057755.9
Gender: FemaleEubacteriales Family XII. Incertae Sedisfamily3891114.4
Gender: FemaleBalneolaeotaphylum269664374.3
Gender: FemaleRhodovibrionaceaefamily119390421.7
Gender: MaleFrancisellagenus181379180.6
Gender: MaleEnterobacter cloacaespecies9813268.5
Gender: MaleKlebsiella pneumoniaespecies113488925.9
Gender: MaleAggregatibacter aphrophilusspecies3594524.5
Gender: MaleDesulfomicrobiumgenus341975.6
Gender: MaleBifidobacterium magnumspecies2123717
Gender: MaleSphingomonasgenus49258817.9
Gender: MaleBifidobacterium pseudocatenulatumspecies379099275.8
Gender: MaleFrancisellaceaefamily181071139.7
Gender: MaleSphingomonadaceaefamily5718198.1
Gender: MaleFibrobacteresphylum2247124934.8
Gender: MaleSporotomaculum hydroxybenzoicumspecies3786013.4
Gender: MaleBifidobacterium boumspecies344145.4
Gender: MaleCystobacterineaesuborder191146.1
Gender: MaleHalochromatiumgenus241185.4
Gender: MaleMitsuokella jalaludiniispecies4002194329.5
Gender: MaleDesulfovibrio vietnamensisspecies233011169.3
Gender: MaleSphingomonadalesorder5816977.8
Gender: MaleDesulfomicrobiaceaefamily341935.5
Gender: MaleEthanoligenens harbinensespecies3963411.8
Gender: MaleSaccharospirillaceaefamily1843848.5
Gender: MaleBifidobacterium tsurumiensespecies2931113.7
Gender: MalePrevotella pleuritidisspecies52140910.8
Gender: MalePrevotella maculosaspecies107918255.2
Gender: MaleBifidobacterium bombispecies345195.5
Gender: MaleSynergistetesphylum301167056.7
Gender: MaleEubacteriales incertae sedisnorank30061116.2
Gender: MaleEubacteriales Family XII. Incertae Sedisfamily384246.4
Gender: MaleRhodovibrionaceaefamily11911045.7

ME/CFS Person: 6 mos since last test / not much movement – IMPROVEMENT!!!

Prior Post: Another ME/CFS person has gone to Firmicutes!

This just came in on Dec 4, 2023

I wanted to share some good news with you.  In the last 3 weeks I’ve noticed my time going to the bathroom has decreased in half and my gut has been less irritable.  Over the last 2 weeks, my mood has steadily improved and I’ve enjoyed more energy than usual.  It appears that your guidance has pointed me in the right direction! 

Note:  I didn’t end up performing the FMT.  

I thought about why my Firmicutes would get to 97%+.  It’s most likely because the majority of the foods I eat are continually pushing my gut towards Firmicutes.  And it could also explain why after adding 5+ daily supplements to push my gut the other direction, it hasn’t worked.   You noted that my being a vegetarian may be acting as a significant counter balance to the direction we’re trying to go.

Besides adding a small amount of meat in the morning, I cut out the foods I eat most frequently.  Bananas, raspberries, blueberries, nut bars.  And then I added in the Seaweed you recommended.  I think the seaweed has made a massive difference and with all these changes implemented collectively, the boat has begun to turn around!
I’m hoping this continues

Backstory

I’m 39 and have suffered from moderate CFS since i was an early teenager.  My major 3 symptoms are low energy, brain fog, and IBS.  My CFS didn’t affect me as much when I was 18, but combined with the effects of aging, I’ve been feeling the fatigue more impactfully the last two years.  

Journey over last 10 months

When I first began working on this in January, my samples showed my Firmicutes at 98%.  That seemed to be the smoking gun as you described it, and I was eager to begin shifting my microbiome.  Over the next 6 weeks I felt markedly better but unfortunately I now believe that was merely a placebo effect.  Once I started to believe the benefits I had received were from a placebo, I rapidly returned to baseline.  Over this time period, I cut out many of the foods that pushed my gut in the wrong direction, and I was taking 4 supplements 2-3x a day.  By my second test 2 mos later, my firmicutes adjusted downwards from 98% to 93%.  In terms of how I felt, it was difficult to assess whether it was better than my baseline.  I was hopeful that it was, but I couldn’t say for sure.

Over the last 6 mos my Firmicutes has reduced from 93% to 89%.  During this time period I continued to cut out foods that were counter-recommended.  I ordered 4 more vitamins & supplements that were in my consensus list, and I was taking 4 supplements 1X/ day, while also rotating the supplements every 4 weeks to prevent resistance.

Once again, it’s difficult to assess now how i feel versus my baseline.  I don’t feel significantly better, that I know.  And while I’m disappointed my sample isn’t improving drastically, the upshot from my perspective is that at least my sample results match how i’ve been feeling.

Reader Addendum After reading

“I’m mostly vegetarian… which may help to explain why after 9 months of supplements I’m partially moving in the wrong direction.  I’ll incorporate the seaweed and increase my red meat.”

Analysis

We have three samples to compare.

Percentage of Percentiles

We see significant shifts between samples with chi2 values increasing (meaning more abnormal) instead of decreasing. What is interesting is that the two earlier samples does not the typical ME/CFS or Long COVID pattern, but the third sample shifted to the pattern of spikes in the 0-9%ile range. This is open to many interpretations; some good and some concerning.

Evaluation Criteria

The numbers below are mixed, some showing improvement, others showing loss.

Criteria1/6/20233/29/20239/12/2023
Lab Read Quality4.35.98.7
Outside Range from JasonH336
Outside Range from Medivere181820
Outside Range from Metagenomics887
Outside Range from MyBioma9915
Outside Range from Nirvana/CosmosId232324
Outside Range from XenoGene383843
Outside Lab Range (+/- 1.96SD)181510
Outside Box-Plot-Whiskers545356
Outside Kaltoft-Moldrup85125181
Bacteria Reported By Lab431553591
Bacteria Over 90%ile493234
Bacteria Under 10%ile4372174
Shannon Diversity Index2.8522.9372.49
Simpson Diversity Index0.0830.0980.101
Chao1 Index85921180715969
Pathogens263540
Condition Est. Over 90%ile1172
Kegg Compounds Low8217311190
Kegg Compounds High13425199
Kegg Enzymes Low359204259
Kegg Enzymes High208311243
Kegg Products Low201124170
Kegg Products High130199158
Kegg Substrates Low195114156
Kegg Substrates High149216162

Forecast symptoms

The top 3 forecasted items are below. See this post: Post Exertional Malaise (PEM) with diminished ME/CFS for more information on forecast symptoms in use. The earliest sample had no forecasts being reliable (i.e. > 60% match). What we also see in that the symptom patterns are becoming stronger. Again, this is usually not desired.

  • 2023-01-06
    • 54.3 % match for Neurological-Vision: Blurred Vision on 35 taxa
    • 52.4 % match for General: Headaches on 42 taxa
    • 50 % match for Immune Manifestations: new food sensitivities on 56 taxa
  • 2023-03-29
    • 65.9 % match for Pain: Pain or aching in muscles on 44 taxa
    • 56.2 % match for Immune Manifestations: Diarrhea on 89 taxa
    • 56 % match for Neurocognitive: Brain Fog on 50 taxa
  • 2023-09-12
    • 65.7 % match for Neurocognitive: Difficulty paying attention for a long period of time on 70 taxa
    • 62.3 % match for Neurocognitive: Can only focus on one thing at a time on 53 taxa
    • 61 % match for Neurological-Vision: Blurred Vision on 41 taxa

Impression and Possible Model

This is the first follow up sample where there was neither clear objective or subject improvement. What we see clearly above was that the microbiome has changed. Subjectively, there was no deterioration reported.

Objectively it seems that the microbiome has been de-noised. This person has had ME/CFS for 20+ years and thus the microbiome dysfunction will evolve. His latest sample changed to the typical pattern for ME/CFS for percentage/percentile chart above. The forecasted symptoms values are increasing for what are likely correct forecasts. The bacteria associated with ME/CFS and IBS are showing themselves better and other bacteria causing noise are diminished.

Going Forward

I first looked at the US National Library of Medicine studies for bacteria reported for the conditions he reported.

  • Chronic Fatigue Syndrome   (1 %ile) 9 of 64
  • ME/CFS with IBS   (9 %ile) 4 of 18

Symptom matching on these is a clear miss. I did note some high matches that are typical symtpoms so I add in the results from these selections:

The result was just 84 unique taxa and we have 5 sets of suggestions in our consensus.

So we fall back to the “Just give me suggestions”. The high priority value was 300 and the low priority value was -405. Adding in special studies suggestions moderated the ranges but most items stayed the same.

It looks the a modified Surf And Turf diet, i.e. Steak and Seaweed (our local Costco does sell a nice seaweed salad that is a regular for me)

The AVOIDS

The avoid values are so high compared to the takes that we need to review them to try reducing or excluding them. The threshold value is -300 (-600/2).

Bottom Line

This has been a challenging set of samples to do an analysis on. I have often used the analogy of going from the port of sickness to the port of health in a sailing ship along a rugged coast. There may be a long series of course corrections needed.

The suggests above are very atypical. Given that there appear to be a lot of noise in his microbiome, we may have some more denoising to do (bring out more the ME/CFS and IBS bacteria into the light). I would advocate attempting to get a course of rifaximin. It has been well used for his IBS diagnosis so there should be little push back from his MD.

Questions and Answers

Q: I’ve read through my new Simplified Suggestions List, and The suggestions of what I need to take and avoid are the same as before…. but the impact score of each was adjusted.  Although you’ve noted in the past that a higher impact doesn’t indicate it works more effectively, it looks from your suggestions that you stick to the highest impact items as there are the most studies to support them, right?

  • Correct. One study may report honey increases a bacteria, and another study report that it decreases the same bacteria. To determine the confidence of a suggestion we look at all reports. If you have 10 honey studies (8 increases and 2 decreases) and one study alone for roasted whale increasing the bacteria; most people will have greater confidence that honey is a better choice to try.

Q: One initial inquiry comes to mind- for complex cases, have you given any additional consideration to (probiotic) enemas as a way to make a big impact, and then to adjust with oral supplements from there?

  • I work from published clinical studies and not from influencers opinion. There is a good summary on WebMD, What to know about probiotic enemas that gives pros and cons.
  • I found Clinical trial: probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN) which had no results (” the number of responders was not significantly higher in the EcN group than in the placebo group”) or results depending on the statistical method used. Thus there is uncertainty about it’s effectiveness.
  • Using commercial/retail probiotics have two significant risks:
    • Very often the declared species is not what is in the bottle, the exception is for those strains that are owned by someone.
    • Often they contain fillers that will be well consumed before they reaches the nether regions. These fillers being inserted here may give a feast to some bacteria that usually do not get much, sparking an unexpected overgrowth.

Q: Below are the supplements I’ve been taking each day.  My plan is to cut out everything that doesn’t have an impact score north of a 150.  Does that sound like a reasonable approach?

  • ground flaxseed.  I took this every day for 4 months and had to stop because it began to make me nauseous. — Try it again at low dosages after one month
  • Luteolin – low positive
  • carboxymethyl cellulosedefinite take
  • Dietary Fiber Cellulose definite take
  • partially Hydrolyzed Guar Gum (SunFiber)remove
  • licorice rootremove
  • Vit B1, B6, B7 — low positive
  • Gaba definite take
  • Vit C remove
  • Melatonin — low positive, suggest you try removing for a week then trying for a week to see if it still help sleep
  • Diosmin – low positive
  • Astragalus – low positive

Answer: The logic is good but I would restrict to only items that are negative. You may wish to revisit the reason that you started each; if it was symptom related and improved — then monitor that symptom and return it if the symptom returns. I have annotated the list above

Reflection

Suggestions could also be described as influencers. There is no need to get religious about taking everything. Take what you are comfortable with is my usual advice. In this case, the person being a vegetarian may have significantly counter-indicated the other influencers. Once the microbiome is normalize, a return to be a vegetarian is viable.

Postscript – and Reminder

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

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

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