This year I have been focusing on a deep review of the code to improve accuracy and to address a variety of issues. The first item was redoing all of the KEGG Derived data (deriving compounds and enzymes at the species level instead of random strains). See KEGG Data being updated

The second item was cleaning up percentile computations on samples for:

• Taxonomy
• End Products
• Compound Produced (KEGG)
• Compound Consumed (KEGG)
• Net Compound (Produced – Consumed) (KEGG)
• Enzymes (KEGG)
• Medical Conditions (US National Library of Medicine)

Combined with this was also implementing Display Levels across menu. See Display Levels.

Existing Menu Items

New Menu Items

Display Level: Public

Display Level: Beginner

Display Level: Intermediate

Display Level: Advance

Outliers Improved

In the earlier version, outliers and full data was on two separate pages. These has been combined into a single page with more options.

Are your abnormal?

Calculations are done for you to indicate the level where values may be out of range by random chance. This is illustrated below.

Bottom Line

I am hoping to have testing completed by the end of March and will then deploy

While there is some research of probiotics (a little, tiny amount may be more accurate for most) with just 38 strains being researched and available for retail sale. While it is a known issue (with no enforcement) for the bacteria species in many probiotics being misidentified (see Deceptive Probiotic Labels or Assessment of commercial probiotic bacterial contents and label accuracy), for the page cited below, we will assume that they are accurate.

Fortunately due to the data on KEGG: Kyoto Encyclopedia of Genes and Genomes we know what products that most species produces, and can infer the quantity of these products/enzymes that are produced.

Emoji codes

• 🍼 Probiotics
• 🏭 Compound Produced – Factories
• 🛍️ Compound Consumed (substrate) – Shopping basket
• 🏗️ Enzymes- Constructs process
• 🦠 Bacteria (general)
• ⚖️ Compare items

Location of Pages

After login, change display Level (top left corner) to a higher level, you will see a new menu item appear with several new pages. This post focuses on the probiotic only.

Each page follows the same pattern. Compound listed on left, estimate of number of units produces by cell and alternative names. The Compound or Enzyme is link to the KEGG page providing more (usually very technical) information.

You can search by just typing the name in the search box. Some examples:

Fast identification of Probiotics for specific purpose

This page shows the compound with links to lists of probiotics. On the far right is the ID from the Organic Acts Tests (OATS – where a match could be identified)

An example of the linked to KEGG page is shown below. This page can be a good starting point for a long and steep learning curve.

Compare Probiotics Pages

These pages allows you to select two different probiotics and see what each produces.

Bottom Line

This provides information that bridges the gaps in published research. If you know what you are trying to increase or decrease, this should provide guidance for you to discuss with your medical professional.

Direct Links

• 🍼🏭 Probiotic Compounds Produced
• 🍼🛍️ Probiotic Compounds Consumed
• 🍼🏭 Changing a Compound by a Probiotic
• 🍼🏭⚖️ Compare 2 Probiotics Products
• 🍼🏗️ Probiotic Enzymes
• 🍼🏗️⚖️ Compare 2 Probiotics Enzymes

Tonight I implemented some downloads of data as Comma-Delimited files which may typically just be double clicked and open in Excel. This information is intended for researchers who wish to develop and test their own models from the data available. If you have to ask what these are, you are a non-nerd. See KEGG for support, not me.

Note that the files download have “Trade Secrets” and (C) 2002 in the name indicating that further distribution of this data is not permitted without written consent. By accessing the data you consent to those restrictions and acknowledge the nature of the information received.

Example of file in Excel

As some of you are aware, I have spent the last few months refactoring how I handled data from KEGG: Kyoto Encyclopedia of Genes and Genomes. This weekend, I just finished pushing the data (over 8 millions rows of data) to the web site.

The computation is based on for each cell Sum(Sum(enzymes x compound produced by enzymes) over species), and the same number of cells of each species.

Nota Bene: There is a lot of rewiring from old tables to new tables that is in process. Some site pages may break.

A reader asked for my opinion on this. This is one of those topics where emotions often run hot and reason can be forgotten. I usually avoid these topics — I hate flame wars.

All of these passion topics, tend to have the following critical factors:

• If those that advocate also sell the product, there is a clear conflict of interest. I will usually assume that their primary motivation is profit that is clothed in the appearance of wanting to help.
• If they do not sell, but often use it, then we have the nasty issue of rose color glasses, selected data picking of their patients. They may have a vested interest in wanting to be right or a pioneer. They usually ignore those that have adverse results (often those people do not return to the people treating — hence they do not see these adverse results or discount them to non-compliance to the treatment plan (blame the patient syndrome).
• Last thing is desperation, especially when standard of medical care fails — people are willing to try anything, regardless of the risk and often very low success (which could have happen at random).

These risks applies to most items where feelings run high.

So, I go over to gold standards sources only (studies published on the US National Library of Medicine aka PubMed).

Helminth and the Microbiome

First item, is that there is risk: “Soil-transmitted helminth infections represent a large burden with over a quarter of the world’s population at risk. Low cure rates are observed with standard of care (albendazole)” [2022]. Hence, viable (living) helminthiases should be avoid. Killed ones (for their chemicals) would be preferred. If things go bad, you are looking at low cure rate!

This study suggests that it could be useful with some gastrointestinal dysbiosis — “Helminth-Induced Human Gastrointestinal Dysbiosis: a Systematic Review and Meta-Analysis Reveals Insights into Altered Taxon Diversity and Microbial Gradient Collapse” [2021], that is two dysbiosis could result in less or more dysbiosis! Dysbiosis roulette anyone?

Helminth infection is included in my microbiome modifiers with 130+ bacteria impacted, see this page (I also include Round-Up! To include it in your suggestions, pick “Prescription – Other“. Remember NONE of the modifier suggestions should be done without medical review).

Please note also that if the treatment including killing them afterwards, that treatment alone may be responsible for positive effects

“There was evidence of treatment-specific effects among the selected studies, such as findings of treatment-associated taxa, including Sphingobacteriaceae and Flavobacteriaceae (26); increased and decreased Actinobacteria and Bacteroidetes, respectively, after placebo comparison (18); mebendazole treatment-induced changes in the diversity and abundance of Collinsella and Blautia (27);”

“Helminth-Induced Human Gastrointestinal Dysbiosis: a Systematic Review and Meta-Analysis Reveals Insights into Altered Taxon Diversity and Microbial Gradient Collapse“

Quick Review of an Advocate

The reader referred me to Lindsey Wells, a naturopath, page on Helminth Therapy. The Hygiene Hypothesis of Autoimmunity is cited which I have touched upon in the past 2015, 2018. To me, many advocates of this hypothesis both over simplify and commercialize it. If you wish to take this hypothesis seriously, then there is only one treatments: live on an organic farm, with a lot of different animals — if your boots are not covered in manure, every day — you are not taking the hypothesis seriously!

“The Amish and Hutterites are U.S. agricultural populations whose lifestyles are remarkably similar in many respects but whose farming practices, in particular, are distinct; the former follow traditional farming practices whereas the latter use industrialized farming practices….Despite the similar genetic ancestries and lifestyles of Amish and Hutterite children, the prevalence of asthma and allergic sensitization was 4 and 6 times as low in the Amish” – i.e. industrialized farming practices resulted in six times (600%) the rate of asthma and allergies. See Innate Immunity and Asthma Risk in Amish and Hutterite Farm Children(2016). This is also echoed in their farm products!!! Amish and Hutterite Environmental Farm Products Have Opposite Effects on Experimental Models of Asthma [2016]. Given a choice of buying groceries from a Hutterite farm or a Amish farm, buy the Amish (non industrialized) groceries!!!!

The bottom line of this page is simple — not a single clinical study was cited. The link to https://biomerestoration.com/hdc/ and where I would expect studies (under “The Science”), there was not one.

And the other site cited: https://helminthictherapywiki.org/wiki/index.php/Helminthic_therapy_research had links to a lot of self-published papers (i.e. not peer reviewed) and just 2 on PubMed.

• Practices and outcomes of self-treatment with helminths based on physicians’ observations [2016]
  • As I stated at the start, this is among the worst form of study because it is prone to the placebo effect plus discontinuation of patients that are non-responders or who have adverse results. They do mention “1% of paediatric patients experienced severe gastrointestinal pains”. No objective measures (labs, etc) were cited. IMHO, a purely subjective report. Note that the journal that it was published in was Journal of Helminthology (I wonder if there is a bias with those doing peer review?)
• Helminth–host immunological interactions: prevention and control of immune-mediated diseases [2012] Which is more of a position paper that was unable to cite any significant human studies, just case reports (which is prone to the same bias as cited above).
  • “Thus, it should come as no surprise that eradicating helminths can result in expression of diseases influenced by these pathways. There are now many animal models representing a diverse range of diseases for which helminths either prevent and/or reverse ongoing pathology. “

And now for Autism

• Helminth therapy for autism under gut-brain axis- hypothesis. [2019] which is a theoretical proposal without any clinical results. It was published in the Med Hypotheses Journal.
  • “I hypothesized that a treatment with Trichuris suis soluble products represents a feasible holistic treatment for autism, and the key for the development of novel treatments. Preclinical studies are required to test this hypothesis.”

Bottom line: there are no clinical studies supporting it use for autism, it is all theoretical. Microbiome Prescription does include it in the options of gut modifiers — so you can objectively see if it is a good fit for an autistic child’s microbiome.

A Critical Criteria: If something has been proposed for 5+ years and fail to produce a positive clinical study then assume there have been several studies done with no positive results.

To me, it is not a rational choice — significant risk of known demonstrated adverse issues with no significant demonstrated positive impact. Odds are that going camping for 2 months in the woods will have a greater positive impact, or better still, work on an organic farm tending chickens, pigs and shoveling manure! Getting involved with 4H may be a good thing in many ways!

Warning: This is for Advance Users and Microbiome Nerds
This year I have been updating KEGG data with an careful audit. The existing KEGG data was strain specific, and the numbers being generated were only for those strains. I have averaged out over the species that these strains belong to so I can compute KEGG data compensating for missing data. Most 16s labs are reasonable complete for species reports but report only a few strains.

The result will be more accurate estimates when I update all of the pages and data computed from the raw data upload.

I am a firm believer in openness — showing which study or source that I obtain the data from. This allows people to independently validate (or nit-pick applicability).

To demo how we can manually get this data…

Request information on an enzyme by entry key, i.e. https://www.genome.jp/dbget-bin/www_bget?ec:1.1.1.10 . From this fulcrum page we get:

• The compounds being produced (Product)
• The compounds being consumed (Substrate)
• Taxonomy — the bacteria having this enzymes

There are also links to a lot more information, while informative, not immediately relevant to Microbiome Prescription.

Clicking on the compounds (CPD: ….) takes you to a description of the compound

Then click on Taxonomy to get the bacteria (and other things it is found in). This will show you an expanding and collapsing tree. Look for Prokaryotes / Bacteria

Expand until you find a strain of interest, all strains will be listed, it is the ones that are in blue, items in red do not have this enzyme. As you see below, this approach has some technical issues, one strain of Escherichia Coli has an enzyme and most of the others do not. To be technically complete, we would need the labs to identify every strain of Escherichia Coli as well as KEGG having all strains — that is unlikely for decades…

Clicking on it will show you the bacteria details as shown below with the all important NCBI Taxon number.

What is happening under the cover…

All of this data is extracted and re-aggerated into 3 main pages:

• Species x (Produces, Consumes)
• Compound x (Producers, Consumers)
• Enzymes x Species

The images are below. Each page allows drill downs

In the case of drill downs to bacteria, we also show a count of the number of enzymes in the bacteria that produces or consumes a compound, as illustrated below:

This is just step 1 – Showing the data

Step 2 is applying it to the samples and re-computing the totals and percentiles. Needless to say, many of these pages will be hidden on the menu to the casual user because it would result in information overload. An advance display level will be required. The above links should always work.

I still have some tuning to do, there are a few thing slightly off… but what is there is reasonably accurate.

A reader with ME/CFS (thus with brain fog) was unable to figure out how to get antibiotics and other (off label) prescription drugs.

This person has a willing MD and in consultation with him, they are wishing to try the Ceclie Jadin protocol that has had over a 70% success rate (when properly done) with ME/CFS. I said “properly done” because I have seen the antibiotics being used continuously (instead of one week on, three weeks off) and without rotation by some MDs that think they can do better (with no clinical experience to support it).

For more information on the Jadin Protocol see:

• Why Jadin’s Antibiotics Protocol usually work — Pasteur Institute got the solution right and the explanation wrong? | CFS Remission [2013]
• C. Jadin Resources | CFS Remission
• Antibiotics for CFS | CFS Remission
• A non-antibiotic proposal for the Jadin Protocol | CFS Remission [2018]

I was first aware of Human Milk Oligosaccharides (2′-Fucosyllactose) being used for health back in the 1960’s. How? Chairman Mao! Let me explained, Mao cites the case of nursing mothers having their child removed so that the mom could literally be milked for the benefit of the warlord’s health. An extreme way of getting HMO — not recommended!!!

For a summary see Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology Nutrients. 2020 Jan; 12(1): 266. for over 20 additional studies, click here

I do not recommend any specific brand — because there have been no studies clarifying the differences between brands, hence no clear evidence on which one is superior for specific conditions. I was first introduced to HMO as a supplement via Holigos, a Danish firm (being of Danish heritage, I was likely biased!) and had several conference calls with their researchers back in 2018 when the first clinical trials were being done in the US.

Needless to say, there are now a few suppliers on the market (I have excluded ‘polluted‘ products, i.e. products mixed with other ingrediants)

• Holigos $40/month (current sale price)
• Layer Origin | PureHMO Super Prebiotic – Human Milk Oligosaccharide (HMO 2’-Fucosyllactose) $27/month
• Ergomax – 2’-Fucosyllactose (2′-FL) – Bio-Identical Human Milk Oligosaccharide (HMO) EUR 24.95 for 100 400 mg capsules. $35/month for the typical 1500-2000 mg/day dosage
• PureHMO Human Milk Oligosaccharide Powder – Bioidentical 2′-Fucosyllactose $45 for 6 weeks. $30/month

A wholesale bulk provider is here (with other providers also out there)

If you come across other **pure** HMO products, please add as a comment.

Based on requests from users, we have implemented display layers to reduce the problem of information saturation reported by some users.

The following levels control what you see on menus and what is hidden

1. Public— Least items, just the bare essentials
2. Beginner— More items, you must be logged in to see these items
3. Intermediate— More choices, you must be logged in to see these items and be a premium member
4. Advance— Almost all choices. Logged in and be a professional member
5. Nerd— All choices, Logged in as a professional and requested access to research items to see these items and be a professional member. Often these items require an advance understanding of the microbiome processes and behaviors

AFTER logging in to Microbiome Prescription, you will see a select box to set your display level. Red items indicate level is not available for your login level. See this page for more information about login level. And this page on why you may wish to donate.

It is one of the factors. Diet is also a factor. Today, there was some sweet studies published on Nature. A few quotes are below.

 Variants at the LCT locus associated with Bifidobacterium and other taxa, but they differed according to dairy intake. Furthermore, levels of Faecalicatena lactaris associated with ABO, and suggested preferential utilization of secreted blood antigens as energy source in the gut. Enterococcus faecalis levels associated with variants in the MED13L locus, which has been linked to colorectal cancer. Mendelian randomization analysis indicated a potential causal effect of Morganella on major depressive disorder, consistent with observational incident disease analysis

Our associations of F. lactaris (P = 1.10 × 10⁻¹²) and Collinsella (P = 2.59 × 10⁻⁸) with ABO suggest a possible metabolic link with blood antigens. 

 In our study, as in previous work^3,5,6,10, the association of LCT variants with Actinobacteria, more specifically Bifidobacterium, is by far the most statistically significant

Combined effects of host genetics and diet on human gut microbiota and incident disease in a single population cohort [2022]

This is well illustrated by this chart in the above study

This study illustrate how the presence or absence of some bacteria species depends on the individual’s DNA as shown in the chart below.

They went onwards and show how diet compounds matter more.

This information has been hinted at in earlier studies:

• “association of a functional LCT SNP with the Bifidobacterium genus (P = 3.45 × 10-8) and provide evidence of a gene-diet interaction in the regulation of Bifidobacterium abundance. ” [2016]

We are still in early days, in some cases you may be able to find studies on PubMed by searching for “SNP {bacteria name}”, for example: “SNP clostridium cellulolyticum” or a google search on similar terms. From which I found:

• Human genetic determinants of the gut microbiome and their associations with health and disease: a phenome-wide association study [2020]

Some charts from this study are shown below: