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.
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!
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);”
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.
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?)
“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. “
“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 wasstrain 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).
Clicking on the compounds (CPD: ….) takes you to a description of the compound
https://www.genome.jp/entry/C00379
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:
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:
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).
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!!!
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)
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
Public— Least items, just the bare essentials
Beginner— More items, you must be logged in to see these items
Intermediate— More choices, you must be logged in to see these items and be a premium member
Advance— Almost all choices. Logged in and be a professional member
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.
Example of choices with PublicExample after logging inShown without a loginAfter Login with a high display levelBacteria Information with public display levelExample of Bacteria Detail Page with high display level
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 work3,5,6,10, the association of LCT variants with Actinobacteria, more specifically Bifidobacterium, is by far the most statistically significant
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.
Note: F. lactaris was formerly known as Ruminococcus lactaris (it is reported on Ombre and Nirvana/Cosmos results)
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:
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.
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