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:

Your body is like a brand new car, everything runs perfectly (assuming no factory recalls). You drive it all over the place and happy with using it. One day, you park it and a stranger’s car hits it (the infection) and knocks it into a ditch filled with water.

The car is recovered from the ditch, taken to a body shop and a local service station mechanic to fix the damage and make sure everything runs. These are the physicians of the car world.

On your next trip over the mountains, pulling your usual vacation trailer, you find a ton of symptoms with the car:

• You smell something, is it mold? is it oil smoking?
• The car does not pull the trailer as easy as before, flooring the gas pedal gets you up to just 20 miles per hour where you did 50 miles per hour before
• You hear creaks when some doors open
• One window occasionally will not go up or down (but does it whenever it is in the shop)
• Some warning lights flashes on for a while and disappear

A car expert comes in. Almost disassemble the car totally! He discover a massive list of issues caused by earlier events:

• The insulation on the electrical system cables has been damaged, circuit boards no longer work to specification, you may need to have all of it replace…
• There is an oil leak
• There is a slow leak of the radiator, hence the engine warning lights occasionally come on
• There is mold behind the panels and under the carpets
• Corrasion is starting on the brakes lines

and the list goes on and on.

You go to your insurance company (almost like Medical Insurance) and find there is only a little coverage. They look at the cost of fully fixing the car, and realize that is far above the blue book value. In fact, they claim that some of issues occurred while the car was insured with a different company, hence they are not responsible (“pre-existing condition”).

In some cases, like some onboard computers, replacement (treatment) is not available or deemed experimental. For example, a fecal matter transplant from a suitable donor.

You walk into your usual local car mechanic (family MD) with the list of items to fix. He looks at you with a blank stare. You may hear one of the following:

• You really don’t need to fix all of those items, I will change the air filter for you and we’ll see how it will run…
• I can’t fix those things. You are just tossing away money
• How much money are you willing to spend, I will try fixing them — no guarantees
• That’s the way it is with older cars, it’s natural!

A human is far more complex than a car. A lot of the issues trace back to the residue from the accident, the microbiome shifts. Some issues can be fixed (for example, removing moisture before consequences happen), some issues may persist (like wheel alignments), others can be ameliorated (for example, perhaps using higher octane gas).

The common mistake is to assume that fixing the dented front fender is all the repair that is needed. This problem is more complex because we are just the drivers (and owner) of the car — but know little about how it functions.

BE VERY CARFUL ACCEPTING Lab ranges for “normal” or if they show an “average” and leaves you to interpret (more likely misinterpret).

One of the things that I have discovered is that often the numbers are NOT a normal curve or a bell curve. Averages and ranges using standard deviations are… well.. the same as saying that the earth is flat. (That use of averages and standard deviation is the standard process for many lab tests – it does not work for the microbiome)

Look at Statistics and Distribution for Prevotella(genus)… It calculates ranges using the KM algorithms…YOU SHOULD NAG THE LAB TO DOCUMENT HOW THEY CALCULATE THEIR RANGES AND THE JUSTIFICATION FOR SHOWING AVERAGE…

You may need a respirator for the amount of smoke that they send your way 

For literature on D-Lactic Acidosis see these posts: [2019] [2015] [2019] or

Increased D-Lactic Acid Intestinal Bacteria in Patients with Chronic Fatigue Syndrome [2009] “This study suggests a probable link between intestinal colonization of Gram positive facultative anaerobic D-lactic acid bacteria and symptom expressions in a subgroup of patients with CFS. Given the fact that this might explain not only neurocognitive dysfunction in CFS patients but also mitochondrial dysfunction, these findings may have important clinical implications.”

There are two approaches that could be used to make this determination:

• Growing the probiotic is a mono-culture environment and measuring it. This is the traditional approach.
• Examining the genes and see if any contain d-lactic acid producing enzymes

I favor the second approach because there can be issues with the reliability of the first one. Some bacteria shift production of metabolites, such as d-lactic acid, based on the availability of food, supplies, other metabolites in the environment (look up quorum sensing) etc. To give a human analogy, a human blacksmith will make iron ploughs but in a war situation, they may switch to guns, spears or armor.

Using the genes approach, we know what they are capable of making (not necessarily what they are making in a specific environment). In the case of the black smith above, his shop may be incapable of casting cannons.

How do I find out data on the second approach? You could go to KEGG: Kyoto Encyclopedia of Genes and Genomes and search there. I have added that information to my Researched Retail Probiotics by Strains page.

On the far right column, you will see that some have a special link under Details.

Clicking this link will take you to the detail page where a link to KEGG data is shown

This page has four sections, two are important for this question: Produces and consume

Just enter lactic acid in the filter box to see whether it is included.

That is it. Remember this will only list bacteria that:

• Have studies on PubMed with this specific strain
• Have their gene sequence on KEGG.jp
• Be available as a retail product somewhere in the world.

Some 3 years ago, in this post I update my earlier post from 2013 and cited “, it is my hypothesis that this alters the microbiome — how, has still to be reported. “. There has been no objective impact on the human microbiome reported yet :-(.

Assuming that depression is partially microbiome caused (see this list of bacteria shifts seen with depression) then we have circumstantial evidence that they are changes (but do not know the details in humans). We do have information from one study on mice (see bottom of post)

• Feasibility and acceptability of a Whole-Body hyperthermia (WBH) protocol [2021] i.e. positive results for treatment for major depressive disorder 
• Whole-Body Hyperthermia for the Treatment of Major Depressive Disorder: A Randomized Clinical Trial. [2016]
• The impact of whole-body hyperthermia interventions on mood and depression – are we ready for recommendations for clinical application? [2019]
• Changes in mood state following whole-body hyperthermia. [2992]
• Far-infrared Ray-mediated Antioxidant Potentials are Important for Attenuating Psychotoxic Disorders. [2019]
  • ” FIR requires modulations of janus kinase 2 / signal transducer and activator of transcription 3 (JAK2/STAT3), nuclear factor E2- related factor 2 (Nrf-2), muscarinic M1 acetylcholine receptor (M1 mAChR), dopamine D1 receptor, protein kinase C δ gene, and glutathione peroxidase-1 gene for exerting the protective potentials in response to neuropsychotoxic conditions.”
• Far infrared radiation induces changes in gut microbiota and activates GPCRs in mice [2019]

Needless to say, the later information has been added to suggestions algorithms.