The Journey Begins with your microbiome

Thanks for joining me!

This is a companion site to the analysis site at: https://microbiomeprescription.com/

The intent of this site to assist people with health issues that are, or could be, microbiome connected. There are MANY conditions known to have the severity being a function of the microbiome dysfunction, including Autism, Alzheimer’s, Anxiety and Depression. See this list of studies from the US National Library of Medicine. Individual symptoms like brain fog, anxiety and depression have strong statistical association to the microbiome. A few of them are listed here.

The base rule of the site is to avoid speculation, keep to facts from published studies and to facts from statistical analysis(with the source data available for those wish to replicate the results). Internet hearsay is avoid like the plague it is.

The Microbiome as a Key to Health

Continue reading “The Journey Begins with your microbiome”

Formal Statement of Microbiome Prescription Model

The following looks at a holisitic approach to generate suggestions for microbiome dysfunctions, symptoms (that may be microbiome associated) and diagnosis (that have microbiome patterns).

This model (or variation there of) is being used by several microbiome testing companies today. See the bottom for example of clinical success.

This post illustrate the process and is not a precise match for current implemenation on Microbiome Prescription (which continuously evolves over time).

Native taxa weights

The first step is to get a weight for each taxa in a sample to identify what should be altered and the importance of each. With shotgun samples, there may be over 7000 different taxa.

The simple first step is to just do a lookup compare to ranges for each taxa (assuming there is sufficient data to compute ranges). Then assign weights based on the sample positioning in the ranges. The key function (tax_range) is often a complex function which may incorporate percentage, percentile, gender, age, diet style, and bacteria hierarchy. For example, Lachnospiraceae bacterium GAM79 may dominate and result in Lachnospiraceae being given no weight and thus expert system rules may be involved.

Conceptually, it is the importance of a bacteria to be shifted with the desired direction of shift converted to a numeric value or vector of values.

This is called a native taxa weights .

Presentation taxa weight.

These native taxa weights are then modified by the presence or absences of diagnosis and symptoms. Conditions are not either/or. A good example is Autism which has a wide spectrum of levels. A bacteria known associated with a condition will likely have an increase weight. A bacteria with no known associations will have a decreased or no weight. This is called a presentation taxa weight. As above, it may be a single value or a vector of values.

Modifier Matrix

We drop the taxa weight into our grid as show below. We show the weigh as a single value below. With a positive weight indicating something to increase and a negative weight indicating something to decrease. The “-1 to 1” indicates a factor.

We now want to maximize the value of the suggestions, i.e.

Sum Over All Bacteria( FactorVit B1 * AmountVit B1 +FactorVit B2 * AmountVit B2 + etc)

Amount often becomes a 1 or 0 (take or do not take) when there is no dosage related data. Factormodifier may be multidimension function on occasion. For example, it values may depend on other factors being selected. This can result in iterations that was the goal the Simula programming language. That is, you get the first naive suggestions(no dependencies), then feed the results into the next iteration.

We can rotate our focus to obtain lists of “to take” and “to avoid”

Sum Over All Bacteria( FactorVit B1 * AmountVit B1)

Factors are often computed from a variety of factors, a few examples:

  • the number of studies reporting a shift (often studies disagree),
  • the magnitude of the shift (and/or P value),
  • the modifier (a specific probiotic strain, a probiotic mixture, a species)
  • context of the studies (humans, mice, pigs, fish, fouls).

Then We enter the Casino…

Rather than arguing over exactly which formulae for weights are correct. We make use of multiple reasonable formulae. Each is run independently and we then apply Monte Carlo modelling to these results.

Linearity is Dangerous To Assume

Our experience is that assuming linearity produces poor results. We found that doing cross validation allows this host of functions to be tuned.

Inferences should also be factored in, i.e. if a modifier alters Lactobacillus genus without details on individual species, most people will assume that it will alter some of the species — unfortunately, there are many studies reporting that lactobacillus increased with some species decreasing and other increasing.

The key issue is dealing with very sparse data that is often heavily conditioned, i.e.

This may explain why wieghts can be vectors of values.

This is where the art of microbiome manipulation comes in.

Clinical Success

Personal Experiences

Via our free for personal use (not commercial/medical office use) we have had many people have done a sample with one of many supported labs, obtained suggestions from the above model and implemented some, and then done a second sample. For everyone that has done this, there has been OBJECTIVE and SUBJECTIVE improvement. I was expecting > 50% only, but we are running 90+%.  For example analysis from those who consented to share, see this collection dealing with Long COVID and Chronic Fatigue Syndrome.

A recent example is shown below using multiple “measuring sticks” from different labs. We see clear improvement.

We also have associations of symptoms to bacteria using our 5000+ donated samples annotated with symptoms. Often the associations exceed P < 0.001 on a lab specific basis. From this data we can give percentage estimates on pattern matching to symptoms. Below is an example for the person shown above.

We see improvement across all of the top symptoms.

We do not look at “cure” (that does happen sometimes), but reduction of symptoms as our criteria.

We have had incidental reports of it appearing to improve the success rate and speed of remission for some cancers.

AI Cross Validation

Additionally we have done cross validation against the literature.  We take the microbiome shifts reported for a condition across multiple studies, run those shifts through the engine, then see how many of the top suggestions have been found to improve this condition according to published studies using those suggestions.  An example is here: Cross Validation of AI Suggestions for Nonalcoholic Fatty Liver Disease .

While not a clinical study as such, it shows that our suggestions appear to agree with results from third party clinical studies.

Which path to walk to heal the gut?

Here we hit a philosophy crossroad (and often a zebra crossing/speed bump of medical practitioner ego and/or arrogance).

  • The road most travelled is focusing on the bacteria most heard about and trying to address them one by one.
    • It keeps the microbiome simple, naively simple. “All you have to do to raise your lactobacillus and bifidobacterium by taking my preferred probiotic mixture [which I will sell to you].”
    • It ignore the need to keep current on recent studies. Chart below is from PubMed. There are almost 25,000 new studies a year or 68 new studies a day.
  • The road that I take is to ignore this chatter, and aim to adjust everything in one pass using mathematical models. No favorites bacteria to focus on (without firm evidence from studies that it is critical for a symptom or diagnosis).
    • I view this approach is most likely to cause desired changes and not chasing this bacteria or that bacteria is isolation.
    • It is accepting microbial interdependence in all of it’s complexity (see below)
    • Using KEGG: Kyoto Encyclopedia of Genes and Genomes data for Metabolites and Enzymes, I do not go down the rabbit hole of some substance being produced by just one bacteria or small set of bacteria. I accept the full width of the microbiome.

Gut Microbiome

The human gut hosts a diverse and complex microbial community:

  • Over 10,000 microbial species have been identified in the human ecosystem, with the majority residing in the gut.
  • Gut bacteria contribute about 8 million unique protein-coding genes, which is 360 times more than human genes. These bacterial genes are critical for human survival, as they enable us to:
    • Digest foods and absorb nutrients that we cannot process on our own
    • Produce beneficial compounds like vitamins and anti-inflammatories

Microbial Interdependence

Microbial interdependence refers to the complex relationships and interactions between different microorganisms in a community, where they rely on each other for survival and functioning. Here are some key aspects of microbial interdependence.

This study illustrates some interactions, one bacteria reduced a lot of other bacteria. Taking a probiotic that reduces this bacteria, and restore other bacteria.

“[Heyndrickxia coagulans] supplementation improved the gut microbiota imbalance by reversing the decreased numbers [caused by E Coli] of EnterococcusClostridium and Lactobacillus in jejunum and Bifidobacterium and Lactobacillus “

Bacillus coagulans prevents the decline in average daily feed intake in young piglets infected with enterotoxigenic Escherichia coli K88 by reducing intestinal injury and regulating the gut microbiota [2023]

Nutrient Sharing

Many microbes cannot produce all the nutrients they need and depend on other microbes to obtain essential compounds:

  • The vast majority of microorganisms require nutrients like amino acids and vitamins that they cannot synthesize themselves.
  • Corrinoids (vitamin B12 and related compounds) are an important example – while most microbes use corrinoids, only a subset can produce them.

Metabolic Cross-Feeding

Microbes often exchange metabolic products in mutually beneficial relationships:

  • Some bacteria break down complex molecules that other species then use as food sources.
  • Waste products from one species may serve as nutrients for another.

Symbiotic Relationships

Many microbes form close, interdependent associations with other organisms:

  • Corals have symbiotic relationships with algal cells living within them.
  • Lichens are symbiotic associations between fungi and algae or cyanobacteria.
  • Gut bacteria in animals help digest plant material the host cannot break down alone.

Community Assembly and Function

Microbial interdependence shapes how communities form and operate:

  • Public goods sharing drives adaptive function loss and the rise of metabolic cross-feeding over evolutionary time.
  • Interdependent patterns that emerge through reductive evolution can make communities more resistant to environmental perturbations.

Ecosystem Roles

Microbial interactions contribute to important ecosystem processes:

  • Soil microbes like mycorrhizal fungi and nitrogen-fixing bacteria form symbioses with plant roots.
  • Microbial communities in oceans, soil, etc. carry out crucial nutrient cycling.

Understanding these complex webs of microbial interdependence is crucial for fields like ecology, medicine, and biotechnology. It highlights how cooperation and mutualism, not just competition, shape biological communities.

Microbial interdependence occurs when different bacterial species rely on each other for growth or survival. This can happen through various mechanisms:

  • Metabolic cross-feeding: One species produces metabolites that another species uses for growth.
  • Signaling interactions: Chemical signals from one species trigger responses in another.
  • Modification of the environment: One species alters the local environment in ways that benefit another species.

Metabolic Interdependence

  • Different bacterial species in the gut perform complementary metabolic functions. For example, some bacteria break down complex molecules that other species then use as food sources.

Colonization and Development

  • Infants acquire their initial microbiome from their mother and other caregivers. Even one-day-old pre-term infants have unique microbiomes that differ from each other and their mothers.
  • The developing infant microbiome is shaped by factors like genetics, environment, and immune system interactions.

Community Dynamics

  • Microbial communities in the human body demonstrate properties like stability (resistance to change) and resilience (ability to return to initial state after perturbation).
  • These dynamics can be studied through longitudinal sampling, for example, before, during, and after events like surgery or antibiotic treatment.

Site-Specific Communities

  • Different body sites host distinct microbial communities adapted to those environments. For instance, the skin, gut, and mouth each have their own characteristic microbiota.

Examples from Research

Several studies have documented cases where the abundance of one bacterial species depends on the presence or amount of another:

  • In the human gut microbiome, researchers have observed that the growth of certain Bacteroides species depends on the presence of specific Ruminococcus species.

Bottom Line

My approach is a holistic approach that attempts to use all of the facts to be considered. At present, over 2.5 million facts or rules. This is based on almost 13,000 studies. The suggestions may not be perfect, but they seem to be both reasonable (strong cross validation is common) and effective for many people.

The alternative paths often is based on “it worked for John Doe, so it should work for you”, or reading a handful of studies (often just one is sufficient for some people to claim being an expert).

When someone tries to “sell you” on their approach ask them:

  • How many of the 10,000+ known bacteria do you consider? What is the evidence for excluding bacteria from consideration?
  • How many of the thousands of metabolites do you consider? What is the evidence for excluding metabolites from consideration?
  • How many studies do you review each month? For myself, it is close to 600 new studies that are identified as worth manual review.

Remember the old analogy of the broad path full of people taking the easy and popular way, versus the narrow path with very few on it.

Advanced Probiotic Suggestions

In a clinical setting, a practitioner may conceptually believe that a patient would benefit from a probiotic. The problem is which one(s). Often the advice is a generic “take a good probiotic”; a suggestion bordering on magical thinking.
Video version below.

Level 1: Using Published Studies

In general, published studies use specific strains of probiotics. Those strains may not be readily available. Often, the suggestion would be to take the same species (with fingers crossed).

For those that wish to avoid this wishful thinking, we have a page listing Research Probiotics available Retail. This allows you to do a quick search. For example, for ADHD we have just two strains listed as shown below. For some conditions, nothing will be found. These are links to studies or reviews that need to be reviewed by the practitioner.

The basic issue is a lack of studies. Comparison studies are usually non-existant.

Level 2: Identifying cause of condition(s) and targeting taxa

Often this is done by using microbiome analysis looking for abnormal levels of bacteria and seeing what will alter them. For example, multiple studies report low levels of Faecalibacterium and high levels of Bifidobacterium for ADHD. As above, we have a search page that links to studies of the impact of different probiotics (and supplements) on each bacteria.

Level 3: Identifying cause using Enzymes and Metabolites

At this point we enter into the Citizen Science world at Microbiome Prescription. Thousands of people have uploaded their microbiome samples from a host of different providers and then annotated the samples with their symptoms and conditions. The data is at MicrobiomePrescription Citizen Science.

The chart below shows the process. The number of abnormal bacteria (too high or too low) is much larger than published studies — not unexpected given the much larger sample size.

Abstraction

We take the microbiome data and transformed it with data from KEGG: Kyoto Encyclopedia of Genes and Genomes to get estimates of enzymes and metabolites or compounds. This data is processed thru a variety of methods to determine associations of the enzymes and metabolites to condition.

What we observe is that at the metabolite level we often have agreement across the three most common providers

At the enzyme level, we do not get this strong pattern

Nor do we get it by the bacteria associated.

Apparent Conclusion

The cause of the symptom or diagnosis appears to be an imbalance of the metabolites. Metabolites levels are the results of multiple bacteria and not a specific bacteria.

Monte Carlo Selection of Probiotics

As a proof of concept, I applied algorithms to the above with the following being the top items suggested (in descending priority). Play with it on Symptom Association Studies.

  • Taxa Based — Select probiotics based on abnormal bacteria shifts
  • Enzyme Based — Select probiotics based on enzymes that are deficient in the condition, but know to be produced by the probiotic
  • Metabolite Based — Select probiotics based on metabolites that are deficient in the condition, which the probiotic impacts
Taxa BasedEnzyme BasedMetabolite Based
clostridium butyricum ,Miya,Miyarisan
Lentilactobacillus kefiri {Kefibios}
bifidobacterium lactis,streptococcus thermophilus probiotic
pediococcus acidilactic {RBB9 PEDIOCOCCUS ACIDILACTI}
Bifidobacterium animalis
Lacticaseibacillus paracasei shirota {Yakult}
bifidobacterium infantis {B. infantis}
lactobacillus helveticus {L. helveticus}
Bifidobacterium animalis subsp. lactis {B. Lactis}
lactobacillus reuteri
bifidobacterium longum,lactobacillus helveticus
Levilactobacillus brevis {L.brevis}
Bacillus pumilus {B. pumilus}
lactobacillus salivarius
Lactobacillus Johnsonii {Lactobacillus Johnsonii}
lactobacillus paracasei,lactobacillus acidophilus,bifidobacterium animalis
lactobacillus paracasei
Streptococcus faecalis, Clostridium butyricum, Bacillus mesentericus {Bio-three}
Lentilactobacillus buchneri {Lactobacillus buchneri}
Lactobacillus kefiranofaciens {Kefir Probiotic}
bifidobacterium pseudocatenulatum li09,bifidobacterium catenulatum li10
mutaflor escherichia coli nissle 1917
enterococcus faecium (probiotic)
Pediococcus pentosaceus
lactobacillus helveticus,lactobacillus rhamnosus
Bifidobacterium longum subsp. longum BB536 {BB536}
lactobacillus plantarum,xylooligosaccharides,
lactobacillus crispatus {L. Crispatus}
Enterococcus faecium sf 68 {bioflorin}
aspergillus oryzae {koji}
lactobacillus casei
Bifidobacterium breve {B. breve}
Latilactobacillus sakei {Lactobacillus sakei}
Arthrospira platensis {Spirulina}
Brevibacillus laterosporus {B. laterosporus }
Lactobacillus jensenii {L Jensenii}
Escherichia coli cryodesiccata {colinfant probiotics}
Finnish Probiotic {Valio Probiotic}
Alkalihalobacillus clausii {Bacillus clausii }
bifidobacterium bifidum
bacillus subtilis,lactobacillus acidophilus
Limosilactobacillus fermentum (probiotic)
Bifidobacterium catenulatum subsp. catenulatum {Bifidobacterium catenulatum}
Escherichia coli:DSM 16441-16448 {symbioflor-2}
lactobacillus plantarum
bacillus subtilis natto {B.natto}
Lactiplantibacillus pentosus {L. pentosus}
Bacillus amyloliquefaciens group {B. Amyloliquefaciens}
Lactococcus lactis {Streptococcus lactis}
Lactobacillus gasseri {L.gasseri}
Pseudomonas fluorescens
Pseudomonas putida
Escherichia coli
Azospirillum lipoferum
Azospirillum brasilense
Cereibacter sphaeroides
Rhodospirillum rubrum
Streptomyces venezuelae
Azotobacter vinelandii
Rhodococcus rhodochrous
Azotobacter chroococcum
Pimelobacter simplex
Acinetobacter calcoaceticus
Priestia megaterium
Streptomyces fradiae
Brevibacillus brevis
Bacillus thuringiensis
Peribacillus simplex
Paenibacillus polymyxa
Bacillus subtilis
Arthrobacter citreus
Brevibacillus laterosporus
Arthrobacter agilis
Bacillus amyloliquefaciens
Alkalihalophilus pseudofirmus
Bacillus velezensis
Bacillus subtilis subsp. natto
Heyndrickxia oleronia
Bacillus pumilus
Shouchella clausii
Cellulosimicrobium cellulans
Bacillus licheniformis
Cellulomonas fimi
Lentibacillus amyloliquefaciens
Clostridium beijerinckii
Corynebacterium stationis
Heyndrickxia coagulans
Micrococcus luteus
Clostridium butyricum
Lactiplantibacillus plantarum
Bifidobacterium longum subsp. infantis
Bifidobacterium breve
Bifidobacterium pseudocatenulatum
Enterococcus faecalis
Bifidobacterium longum subsp. longum
Enterococcus faecium
Lacticaseibacillus paracasei
Lactococcus cremoris
Bifidobacterium longum
Lactiplantibacillus pentosus
Bifidobacterium breve
Bifidobacterium pseudocatenulatum
Bifidobacterium longum subsp. infantis
Bifidobacterium bifidum
Bifidobacterium longum
Bifidobacterium catenulatum
Bifidobacterium adolescentis
Bifidobacterium longum subsp. longum
Bifidobacterium animalis subsp. lactis
Pediococcus pentosaceus
Pediococcus acidilactici
Lactobacillus acidophilus
Brevibacillus brevis
Escherichia coli
Lactobacillus delbrueckii subsp. bulgaricus
Limosilactobacillus reuteri
Lactobacillus gasseri
Lactobacillus jensenii
Lactobacillus johnsonii
Enterococcus durans
Lactobacillus helveticus
Pseudomonas putida
Streptococcus thermophilus
Limosilactobacillus fermentum
Ligilactobacillus salivarius
Levilactobacillus brevis
Lactobacillus kefiranofaciens
Lactobacillus crispatus
Lentilactobacillus kefiri
Leuconostoc mesenteroides
Arthrobacter agilis
Micrococcus luteus
Lactococcus cremoris
Leuconostoc lactis
Alkalihalophilus pseudofirmus
Lactococcus lactis
Priestia megaterium
Corynebacterium stationis
Acinetobacter calcoaceticus
Anaerobutyricum hallii
Brevibacillus laterosporus
Lactiplantibacillus plantarum
Streptomyces fradiae
Pimelobacter simplex
Cellulomonas fimi
Lactiplantibacillus pentosus
Bacillus licheniformis
Lacticaseibacillus casei
Lacticaseibacillus rhamnosus
Lentibacillus amyloliquefaciens

Some probiotics are high on all three lists, for example: E.Coli. Others are not. I am inclined to using enzymes as the preferred abstraction. Metabolites have a very nice clustering, but at present deriving probiotics is not as clean and simple as desired. A more complex model is needed.

What have we learnt:

  • There may not be studies on probiotics for a specific condition
  • There are studies on probiotics that shifts some taxa. Things can become complex when there are multiple taxa in scope (as well as reliability of taxa identification)
  • From the KEGG Enzymes estimated from a sample, we can derive the enzyme producing probiotics that may conceptually help
    • Note: Organic Acid Test (OATS) report on many of these enzymes and can be used to validate estimates. Additionally, OATS tests can be used to select probiotics for the reported deficiencies
  • From the KEGG metabolites estimated from a sample, we can supplement with the deficiency where practical, or look for probiotics that produces deficient metabolites.

The Enzymes and Metabolite approaches should produce reasonable candidates for future clinical studies.

Patient Specific Suggestions

The above exploration analysis was done ignoring the amount of bacteria in a specific example (and thus enzymes and metabolites). It also ignored whether there is duplication of enzymes and metabolites in the probiotics. Ideally, you want a full coverage of enzymes and metabolites.

https://youtu.be/Z9qXyEVQlus

Medical Beliefs vs Actuary Tables

I have known for years that conventional MD knowledge often trail science by generations. It means that patients need to educate themselves (and in some cases, their MD). The first example is simple:

Stress being the Cause of Ulcers

The discovery that ulcers are caused by bacteria, specifically Helicobacter pylori, was made by Australian researchers Barry Marshall and Robin Warren in 1982. They identified H. pylori as a major cause of gastritis and peptic ulcer disease, challenging the prevailing belief that stress and lifestyle factors were the primary causes of ulcers.[23 years of the discovery of Helicobacter pylori: Is the debate over?]. In 1994, the National Institutes of Health (NIH) held a consensus meeting that concluded the key to treating gastric and duodenal ulcers was the detection and eradication of H. pylori. Then it spent the next decade educating MDs.

But wait! John Lykoudis, MD. after treating himself for peptic ulcer disease with antibiotics in 1958 and finding the treatment effective, Lykoudis began treating patients with antibiotics. After experimenting with several combinations of antibiotics he eventually arrived at a combination which he termed Elgaco and which he patented in 1961. So it took 4 decades from demonstration to acceptable practice.

BMI and Life Expectancy

If you go to CDC Calculator for BMI, Age is not a factor

“One BMI will rule them all”. Except, if we are talking about health — this is wrong

Older adults with BMI <25 and >35 kg/m2 were at a higher risk of a decrease in functional capacity, and experienced gait and balance problems, fall risk, decrease in muscle strength, and malnutrition. Data from this study suggest that the optimum range of BMI levels for older adults is 31–32 and 27–28 kg/m2 for female and male, respectively.

Going to What is the Optimal Body Mass Index Range for Older Adults? [2022]

Where as CDC shows this evaluation and would encourage older people to move to an unhealthy BMI. As a FYI, I am at 31.7 and working to reduce to 28 using probiotics see Probiotics, Obesity and Diabetes.

Blood Pressure and Stroke Risks

For those over 65, a recent study Association of Blood Pressure With Stroke Risk, Stratified by Age and Stroke Type, in a Low-Income Population in China: A 27-Year Prospective Cohort Study [2019] found some very interesting results. If you over 65 and have BP < 130, you actually have an increased risk of stroke (i.e. 1/.80) = 25% greater odds of having a stroke then if you were in the 130-140 range. In the 140-150 range, it is a toss up — with odds of one type of stoke still low and the other marginally increasing.

Among older Japanese adults with isolated systolic hypertension and baseline SBP values ≥160 mm Hg, the on-treatment SBP level at which CVD event risks and all-cause mortality were minimized was 130 to < 145 mmHg. On-treatment SBP values of < 130 or ≥145 mmHg were associated with increased CVD event risk and all-cause mortality.

On-Treatment Blood Pressure and Cardiovascular Outcomes in Older Adults With Isolated Systolic Hypertension [2017]

Isolated systolic hypertension (ISH) is a condition characterized by an elevated systolic blood pressure (the top number) of 130 mm Hg or higher, while the diastolic blood pressure (the bottom number) remains below 80 mm Hg

Bottom Line

The reality is that your MD knowledge may be stale and not in agreement with the latest research. Use the US National Library of Medicine to find the latest research — be specific for age and gender in your research. Share it with your MD.

Long COVID and Hypoxia (brain fog)

Long COVID [Post COVID Syndrome] is likely an immature variant of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). I use the term immature because typically a ME/CFS diagnosis comes 2-10 years after on-set. Between onset and a later static state, the microbiome is a state of constant transition attempting to reach a new stable state.

Doing a search on Pub Med for “Long COVID hypoxia”, we get over 200 hits. Searching for “Long COVID coagulation”, we get over 300 hits! The following are quick notes to sketch out avenues for people treating Long COVID, especially patients with brain fog. I have cited classic ME/CFS literature and matching literature on Long COVID. This is a page in progress and may be updated periodically.

How can Hypoxia happen?

There are many ways, here’s a recap:

  • Coagulation Issues: Often it is an inherited coagulation defect that flares as a side-effect of post COVID changes (likely of the microbiome). See Thick Blood, Clots dimension of CFS.
    • Coagulation is a complex process and “taking a baby aspirin” is NOT a cure all.
    • The defect may be in just one or several of the Roman Numeral items shown below. (From Coagulation Cascade)
    • The result is often called “Thick Blood”
    • See this Johns Hopkins “What Does COVID Do to Your Blood?

Some Signs of the Above

  • Objectively measured abnormalities of blood pressure variability in CFS[2012]
  • Lower blood pressure in sleep[2011]
  • Lower blood pressure[2009]
  • Rapid Heart Beat (Tachycardia) (more info) – because of lower delivery per heart beat, the heart beats more trying to deliver more oxygen
  • Small heart on X-Rays
  • Low Iron Levels (definition of low should likely be below average, not the lab ranges)
  • Saturated O2 level being slightly low

Treatment Options

Hemoglobin improvement

Coagulation

Microbiome

Keeping Supplement Costs Under Control

A few years ago I wrote A Frugal List of Supplements for ME/CFS using knowledge at that time trying to rank order supplements that may help by best cost. Today a similar question came up. I am retired (72 y.o.) and working part time with a variety of complex conditions in the household so getting the right stuff at reasonable cost is a priority.

In this post I will share what our current strategies are and illustrate cost savings. For making our own capsules, I have ignored the cost (since it is low).

Example #1 Supplement Hesperidin

Choice #1: Off the shelf: 13.57 / ( 0.500 g x 60) = $0.45 per gram

Choice #2: Bulk Powder off Amazon. $16.96/ 100 grams = $0.17 /gram

Choice #3: Buying direct from a manufacturer in bulk (but certified organic): 24.14 /100 = $.24 / gram (with free shipping)

Example #2 Lactobacillus Plantarum

Choice #1: Off the shelf: 30 capsules with 10 BCFU: $12.42 / (30 x 10) = $0.04 / BCFU

Choice #2: Bulk Probiotics as powder: 169.17 / (400 x 100) = $0.004 per BCFU. Lower package sizes available at slightly higher cost per BCFU.

Choice #3: Buying direct from a manufacturer in bulk (Organic and typically manufactured within 2 weeks of shipping): $138.73 / (20 x 1000) = $0.007/BCFU. Lowest package is $0.02/BCFU

A key issue is probiotics is time since manufacture, abuse in storage (i.e. not kept is fridges in transit and storage — if you look “behind the scenes” at many health food stores, you will see boxes of probiotics just kept in the back, not refrigerated. They are then put it into the display refrigerator as needed). See Probiotics — what is advertised may not be what you get

Example #3 Herb Turmeric

Choice #1: Off the shelf: $12.49/(1 gm x 60) = $0.21 / gram

Choice #2: Bulk – from Amazon (note this is Organic, above is not): $14.99 / 907g = $0.016 / gram

Choice #3: Oversea supplier (also organic): $18.11 / 100gram = $0.18/gram

Bottom Line: Up to 90% reduction in Supplement Costs is possible

There are always other factors — for example, some probiotics may only be available from just one supplier (i.e. L. Jensenii, E. Coli Nissle 1917). Do you want it to be Organic? Degree of trust in manufacturer, supply chain handling, seller’s handling (I deemed it very unlikely that Probiotics sold by Amazon are refrigerated, more likely just sits in their warehouses until sold).

Also, be pragmatic on likely duration of use. Don’t over buy to “save money” and have it sitting on the shelf forever…

Remember: Most supplements are high profit margins. At least one supplement seller who also sells microbiome testing kits is suspected to sell their kits at below cost because of the profit from selling the supplements to the same customers.

Our own experience with Maple Life Sciences probiotics have been awesome. We see changes in stools within 48 hours when we rotate between probiotics.

Probiotics, Obesity and Diabetes

A study demonstrated Fecal Microbiota Transplantation (FMT) alone can change a skinny mouse into a fat one is detailed in the research published by the journal Science. In this study, researchers transplanted gut bacteria from human twins discordant for obesity into germ-free mice. The mice that received gut bacteria from obese twins grew fat, while those that received bacteria from lean twins remained lean. This experiment provided compelling evidence that gut microbiota can influence body weight and adiposity independently of diet or other factors. Visual below of mice feed identical diet.

My own experience is loosing 30 pounds from the addition of a specific probiotic (Akkermansia) over a year without a change of diet. IMHO, a change of diet along may not do it. Often it takes two things: changing the diet AND changing the bacteria in the gut.

Literature

Probiotics that have the best actual evidence

Note that some probiotics can result in weight gain, so taking random ones is not the way to do it. Many of the studies found effective using probiotics mixtures included Lactobacillus plantarum

Diabetes

While many studies show promise, the evidence is still mixed, and more long-term research is needed to determine the most effective probiotic strains and protocols for diabetes management [Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis] – study was pre-Akkermansia availability.

And

Bottom Line

My (incomplete) review of the many many studies suggests that four species of probiotics are the most likely to help with Obesity and Diabetes. Below are links to manufacturers that directly sell my preferred single strain probiotics. This means that you will get the probiotics within weeks (or days) of being manufactured (i.e. Very fresh and live probiotics).

Suggested daily dosage is a therapeutic 50 BCFU/day for the Lactobacillus, and likely a capsule of Akkermansia muciniphila (Pendulum is the established provider).

For the Lactobacillus, I find using powder dissolved in a glass of warm water works very well. It often has a side effect of inhibiting wanting to have a treat and gives a satisfied feeling in the gut. Taking them as capsules do not seem to have that effect.

Microbiome Prescription is already in conformity to the new EU AI laws!

We are likely the sole firm claiming the use of AI for microbiome analysis that is in conformity today. Most firms in this area that claim using AI, refuse to even disclose which type of AI that they are using. Since our founding, we have been OPEN DATA. The logic used for every suggestion is show and links to every data source. We are about to file patents for our proprietary, PATENT PENDING, algorithms – meaning that shortly even the algorithms will be available for inspection.

Our core AI model is an old classic: fuzzy logic expert systems.

The foundations of fuzzy logic were laid in 1965 by Lotfi Zadeh, a professor at the University of California, Berkeley. In his seminal paper “Fuzzy Sets”, Zadeh introduced the concept of fuzzy set theory, which allows for degrees of truth rather than the classical binary true or false [A brief History of Fuzzy Logic].

The concept of expert systems, which are computer programs designed to emulate the decision-making abilities of a human expert, began to take shape in the 1960s. One of the earliest and most notable examples was MYCIN, developed in the early 1970s at Stanford University. MYCIN was designed to diagnose bacterial infections and recommend antibiotics based on a set of if-then rules derived from expert knowledge. [Knowledge Discovery from Medical Data and Development of an Expert System in Immunology]

Biofilms, Histamine and D-Lactic Acid

I have had a few emails asking if I am over-flagging these issues on MicrobiomePrescription.

I used Perplexity.AI to get some numbers…. here is what was reported (with references to sources). Given the typical reasons that people get microbiome samples, the rates appear reasonable.

  1. The National Institute of Health (NIH) statistics indicate that biofilm formation is present in about 65% of all bacterial infections and approximately 80% of all chronic infections.
  2. In the context of human health, biofilms are responsible for about 80% of bacterial infections

https://www.perplexity.ai/search/what-percentage-of-microbiome-fLRJ2SghTLCSWDdlo2AGKw#0

  1. D-lactic acidosis is considered rare in humans overall, but it may be underdiagnosed. Some experts suggest it should be looked for more often in cases of unexplained metabolic acidosis.
  2. It is most commonly associated with short bowel syndrome (SBS). The incidence of SBS is estimated at approximately 2 persons per million per year. While not all SBS patients develop D-lactic acidosis, they are at higher risk.
  3. In patients with short bowel syndrome, D-lactic acidosis appears to be a relatively frequent complication. One study found that all 29 SBS patients examined had experienced neurologic symptoms associated with D-lactic acidosis at some point
    [NOTE: SBS have a very high incidence of SIBO [src], so SIBO likely have an increased risk of d-lactic].

https://www.perplexity.ai/search/what-percentage-of-microbiome-fLRJ2SghTLCSWDdlo2AGKw#1

  • Histamine intolerance is estimated to affect approximately 1-3% of the general population. However, some experts suggest this number could be higher as the condition is often underdiagnosed.
  • Among people with digestive symptoms or conditions like IBS, IBD, and Crohn’s disease, a surprisingly high 30-55% may have histamine intolerance.
  • One study found that diamine oxidase (DAO) deficiency, which is associated with histamine intolerance, was present in up to 44% of the control population.
  • A more dramatic estimate suggests that histamine intolerance may affect 50-60% of the population, according to one source. However, this figure seems significantly higher than other estimates and may need further verification.
  • In people with digestive symptoms, one study showed that 30-55% also have histamine intolerance.
  • https://www.perplexity.ai/search/what-percentage-of-microbiome-fLRJ2SghTLCSWDdlo2AGKw#2

Most significant genus associated to medical conditions

A reader asked, Which genus should I give highest priority in general?

This is an easy answer using the Conditions populated from studies on the US National Library of Medicine on 127 different conditions. The results are below for those that are seen in at least 10% of conditions.

Below that is a table showing the direction of shifts.

Taxa NamePercentage Of Conditions with Shifts
Bifidobacterium55
Prevotella54
Bacteroides52
Faecalibacterium51
Lactobacillus47
Blautia44
Ruminococcus43
Streptococcus41
Roseburia40
Escherichia40
Clostridium38
Parabacteroides37
Coprococcus34
Alistipes33
Eubacterium31
Shigella31
Veillonella30
Akkermansia29
Fusobacterium27
Dorea27
Enterococcus27
Anaerostipes26
Dialister25
Collinsella25
Haemophilus25
Klebsiella25
Odoribacter25
Megamonas23
Bilophila22
Desulfovibrio22
Subdoligranulum22
Lachnospira21
Turicibacter21
Phascolarctobacterium20
Eggerthella20
Enterobacter20
Butyricicoccus18
Oscillibacter18
Porphyromonas18
Megasphaera17
Lachnoclostridium16
Sutterella16
Staphylococcus16
Butyricimonas16
Actinomyces16
Oscillospira15
Romboutsia14
Parasutterella14
Barnesiella14
Campylobacter14
Anaerotruncus14
Paraprevotella14
Methanobrevibacter14
Catenibacterium13
Butyrivibrio13
Flavonifractor13
Citrobacter13
Coprobacillus12
Adlercreutzia12
Parvimonas12
Rothia12
Pseudomonas12
Acidaminococcus11
Fusicatenibacter11
Gemella11
Corynebacterium11
Agathobacter11
Ruminiclostridium11
Lactococcus11
Weissella11
Slackia10
Alloprevotella10
Eisenbergiella10

Direction Of Shifts for each bacteria

For some it is balanced, for others only one direction is significant.

  • “H” means that this genus for medical conditions are abnormally high for people with a condition
  • “L” means that this genus for medical conditions are abnormally low for people with a condition
  • NOTE: For some conditions, both High and Low are reported, i.e. the population of this genus becomes abnormal. For details see: https://microbiomeprescription.com/Library/PubMed
Taxa NameDirection of shiftPercentage
ActinomycesH13
AgathobacterL8
AkkermansiaH21
AkkermansiaL15
AlistipesH20
AlistipesL21
AnaerostipesH11
AnaerostipesL17
AnaerotruncusH11
BacteroidesH37
BacteroidesL37
BarnesiellaL9
BifidobacteriumH32
BifidobacteriumL43
BilophilaH14
BilophilaL9
BlautiaH28
BlautiaL27
ButyricicoccusL16
ButyricimonasH8
ButyricimonasL10
ButyrivibrioL11
CampylobacterH13
CatenibacteriumH8
CitrobacterH10
ClostridiumH25
ClostridiumL20
CollinsellaH18
CollinsellaL12
CoprobacillusH10
CoprococcusH15
CoprococcusL28
CorynebacteriumH8
DesulfovibrioH18
DialisterH11
DialisterL18
DoreaH18
DoreaL15
EggerthellaH17
EnterobacterH14
EnterococcusH21
EnterococcusL13
EscherichiaH37
EubacteriumH12
EubacteriumL26
FaecalibacteriumH18
FaecalibacteriumL44
FlavonifractorH12
FusobacteriumH22
GordonibacterH8
HaemophilusH13
HaemophilusL15
KlebsiellaH23
LachnoclostridiumH12
LachnospiraL14
LactobacillusH28
LactobacillusL31
MegamonasH14
MegamonasL14
MegasphaeraH13
MethanobrevibacterH13
NeisseriaH8
OdoribacterH17
OdoribacterL12
OscillibacterH14
OscillospiraH11
ParabacteroidesH29
ParabacteroidesL16
ParaprevotellaH8
ParaprevotellaL8
ParasutterellaL11
ParvimonasH8
PhascolarctobacteriumH13
PhascolarctobacteriumL13
PorphyromonasH14
PrevotellaH40
PrevotellaL36
PseudomonasH9
RomboutsiaL11
RoseburiaH13
RoseburiaL34
RothiaH11
RuminococcusH27
RuminococcusL25
ShigellaH30
StaphylococcusH14
StreptococcusH36
StreptococcusL14
SubdoligranulumH11
SubdoligranulumL15
SutterellaH11
SutterellaL8
TuricibacterH11
TuricibacterL14
VeillonellaH21
VeillonellaL12