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”

ME/CFS – short live recovery from Myorisan 

Back Story

I have severe /very severe ME/CFS and have noticed partially dramatic changes (although short lived) when taking a probiotic, especially Myorisan [Clostridium butyricum].

Analysis

Sample Comparison

My general impression is that this person has lost some ground in terms of reference ranges(more found at extremes), but has gained ground with Kegg Compounds and Enzymes (less ones at extremes).

To get better insights, I added a Pattern Matching Comparison. Only symptoms marked in either samples are compared. We see some improvement happened.


Going Forward

My updated starting point with the new UI when the person has one or more conditions picked to [Beginner-Symptoms: Select bacteria connected with symptoms]. As shown below, we have a large number of symptoms matching the patterns from our data analysis. This suggests that we are likely to pick the right bacteria to focus on (based on statistical evidence – which any skilled person can reproduce using data on https://citizenscience.microbiomeprescription.com/).

The top suggestions are below

As well as the top avoids

Probiotics

The top probiotics using published studies on PubMed were:

With the new UI, we also have probiotics computed from RNA/DNA of your microbiome and probiotics. Usually I select only low compounds (i.e. some bacteria will be inhibited from starvation).

As is typical with ME/CFS, the top ones are E.Coli probiotics.

I checked each of the PubMed suggestion to see their relative impact and put in [ ] below.

I would start with aor / probiotic-3, then one of the Lactobacillus reuteri , then Lactobacillus gasseri and end with miyarisan. While aor and miyarisan both contain the same bacteria species, they are different strains.

  • Food avoid list is high in food containing fiber (in agreement with diet style)

Bottom Line

The user report of improvement with miyarisan and the suggestions are a nice agreement to see. The issue of being short termed is not atypical to see when there is no rotation of probiotics and antibiotics.

IMHO, probiotics should be viewed as natural antibiotics. As with all antibiotics, antibiotic resistance (probiotic resistance) may developed from continuous use. For Lactobacillus reuteri we have Reuterin; for Clostridium butyricum we have: CBP22, Butyricin 7423, Butyricum M588, Perfringocin 1105. (see Effects of Clostridium butyricum as an Antibiotic Alternative [2023]).

The same applies to herbs and spices with antibiotic characteristics… resistance will often develop from continuous use.

Postscript and Reminder

As a statistician with relevant degrees and professional memberships, I present data and statistical models for evaluation by medical professionals. I am not a licensed medical practitioner and must adhere to strict laws regarding the appearance of practicing medicine. My work focuses on academic models and scientific language, particularly statistics. I cannot provide direct medical advice or tell individuals what to take or avoid.My analyses aim to inform about items that statistically show better odds of improving the microbiome. All suggestions should be reviewed by a qualified medical professional before implementation. The information provided describes my logic and thinking and is not intended as personal medical advice. Always consult with your knowledgeable healthcare provider.

Implementation Strategies

  1. Rotate bacteria inhibitors (antibiotics, herbs, probiotics) every 1-2 weeks
  2. Some herbs/spices are compatible with probiotics (e.g., Wormwood with Bifidobacteria)
  3. Verify dosages against reliable sources or research studies, not commercial product labels. This Dosages page may help.
  4. There are 3 suppliers of probiotics that I prefer: Custom Probiotics Maple Life Science™Bulk Probiotics: see Probiotics post for why
  5. My preferred provider for herbs etc is Maple Life Science™ – they are all organic, fresh, without fillers, and very reasonably priced.

Professional Medical Review Recommended

Individual health conditions may make some suggestions inappropriate. Mind Mood Microbes outlines some of what her consultation service considers:
A comprehensive medical assessment should consider:

  • Terrain-related data
  • Signs of low stomach acid, pancreatic function, bile production, etc.
  • Detailed health history
  • Specific symptom characteristics (e.g., type and location of bloating)
  • Potential underlying conditions (e.g., H-pylori, carbohydrate digestion issues)
  • Individual susceptibility to specific probiotics
  • Nature of symptoms (e.g., headache type – pressure, cluster, or migraine)
  • Possible histamine issues
  • Colon acidity levels
  • SCFA production and acidification needs

A knowledgeable medical professional can help tailor recommendations to your specific health needs and conditions.

An Anhedonic Reader

Back Story

Started feeling slightly tired in 2014, but I didn’t pay much attention to it. Around 2016 I am told the fatigue I am suffering from is likely caused by depression and so I take various SSRIS for 4 years. They made me anhedonic[inability to feel pleasure] and actually caused fatigue to somewhat worsen.

In 2022 after recovering from covid, I take aj immune boosting supplement to try and finally break free from the fatigue I was suffering. It actually worked and brought me back to life, which is when I decided ro come off my SSRI.

This was a mistake. It made me even more anhedonic and caused me to crash. I have not recovered since.

Lately, I have been dealing with actinic acid build up which is very weird for me as I was a professional athlete. 

Analysis

This has been sitting in my backlog (waiting for feedback from reader). I just discovered that he has since done a second sample, so this is a revision and update.

Comparisons

I do not know how many of the suggestions made in the earlier draft was done. Note that we went from 760 bacteria down to 447 (just 58%). So for most of the numbers below, we need to see at least a 50% drop in bacteria for something to be an improvement. Most of these measures failed to make this criteria.

We have added a new comparison table of changes of fit to reported symptoms. This also show a general loss of ground.

With the new UI appearance, I am also trying to keep the analysis simple by not obfuscating with too many measures.

Going Forward

I am going to do [Beginner-Symptoms: Select bacteria connected with symptoms] and then [Probiotic computed from Kyoto Encyclopedia of Genes and Genomes compounds].

We ended up with 8 bacteria being selected. The top suggestions are shown below

With best probiotics being: CustomProbiotics.com / L. Salivarius Probiotic Powder and Bulk Probiotics / L. Helveticus Probiotic Powder.

I decided to also try [Novice: Just tell me what to take or avoid] which increased the selected bacteria to 23. There are some similarities and differences (to be expected from the targeted bacteria increasing from 8 to 23)

The probiotics suggested were the same.

Going to KEGG Probiotics

We have a very different list. One jumps out: E.Coli probiotics. The number is the number of low compounds that it increases.

Checking with the earlier suggestions we see

My Probiotics Bottom Line

I would run with these 4 probiotics (taking each for one week and then rotating to the next)

Why did I go with two from KEGG? The reason is simple — this is computed across the entire microbiome and does not depend on someone doing studies. The two other ones are based on published studies.

All of the above are typically deficient in samples (or assumed by some medical practitioners to be the cause of issues). This is not the case, and suggestions reflect this.

Items to Take

I would work off the two lists above – there is a reasonable amount of agreement. I note that fiber and high fiber foods are common on both of to-avoid list as is wheat, gluten (and bifidobacterium probiotics).

General Guidance

For items to take, remember that goal is to disrupt the dysbiosis. This means subjecting it to constantly changing “shocks” so it is unable to adapt. This has been shown to be effective when dealing with antibiotics (i.e. rotating between different antibiotics with breaks is more effective than taking the same antibiotic continuously). It likely applies to probiotics and herbs.

Postscript – and Reminder

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

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

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

ME/CFS Patient continues the trek to recovery

Prior Posts

Dealing with ME/CFS and many microbiome dysfunction is rarely a short journey

Recent Story

Some supplements that I have been taking since the last test:

  • Tetracycline 
  • Clove 
  • Holy basil (Neem)
  • Augmentin + Bromelain 
  • Grapefruit seed extract 
  • Monolaurin
  • Apple peel powder 
  • Thyme

My symptoms:

  • Still get the red nose (some form of rosacea). 
  • Still feel fatigued (both physically and mentally). But it is better than before.
  • Feeling stressed. But it is better than before.
  • Brain fog.
  • Bloated.
  • Lots of gas – I fart and burps a lot. 
  • Issues with allergies (itching eyes, stuffed nose and itchy skin)

Video

Analysis

We will start with the high-level comparison. Note that some numbers will change with time. There are no major changes. Since the latest sample reports 20% more bacteria, many counts are expected to be 20% higher – for example: Thorne Ranges: old: 230 + 20% = 276, with the seen count being 253 (so an apparent improvement although the number went up)

Criteria9/2/20241/22/20249/12/20232/22/20238/11/20223/25/202212/3/20218/31/2021
Lab Read Quality9.17.93.59.75.56.23.67.8
Outside Range from GanzImmun Diagostics1616161515171720
Outside Range from Lab Teletest23 20 202424222225
Outside Range from Medivere1416161515151519
Outside Range from Metagenomics67799778
Outside Range from Microba Co-Biome32277111
Outside Range from MyBioma6577778
Outside Range from Nirvana/CosmosId2120202323181821
Outside Range from Thorne (20/80%ile)253230198223223217217246
Outside Range from XenoGene3232 243232363639
Outside Lab Range (+/- 1.96SD)121510119914
Outside Box-Plot-Whiskers4852564236425942
Outside Kaltoft-Moldrup113 123 70139567859140
Bacteria Reported By Lab600508399666478613456572
Bacteria Over 85%ile4852      
Bacteria Under 15%ile118157      
Pathogens23 26 253023392430
Condition Est. Over 85%ile25      

There is a new comparison table added that compares sets of symptoms bacteria for symptoms reported in either sample. This is a thought experiment on a different way of evaluating the microbiome, i.e. are symptom bacteria reducing. Remembering that we have 20% more bacteria reported, the improvement may be slightly under-reported.

Going Forward

My current preference is to use symptom associations suggestions with KEGG suggested suggestions. This assumes that the person has added their symptoms.

Using Entered symptoms

Since this person has access to antibiotics, I opted to include all classes of modifiers. We have 38 bacteria selected — a reasonable number

The suggests were a nice mixture for ME/CFS. Typically, I see the top being just antibiotics, in this case we have several probiotics there.

And suggested retail probiotics are:

Using Diagnosis and PubMed

Using a diagnosis provides less precise filtering compounded by different labs (with different identification of bacteria). If the person is using a lab that lacks a large number of annotated samples from that lab, then it is the best path.

The suggested path is to go down the list and pick the ones that has the highest value(s) that agrees with one or more of the diagnoses that you have.

In this case we have only 4 bacteria in the selection, so the suggestions will be likely more generic than specific.

There are no antibiotics in this list

The probiotic list is below. It has some similarities to the above list.

Using KEGG Derived Probiotics

This is an experimental approach that attempts to do a metagnòmia approach from the available data. We estimate which compounds are too high or too low. Then we match them to probiotics which produce or consumes them. Postbiotics can be used for items that are too low. There is no filtering of any type; we look at the entire microbiome.

The results are different — as to be expected. Why expected? The prior ways depended on studies being done what each probiotics bacterium does. Often there are no studies. This way uses the DNA/RNA sequences of everything and thus we do not need studies.

I usually focus on too low, with the assumption that a surplus will just be ignored or has less impact (i.e. starvation versus obesity) We can see where there is agreement between the lists.

  • aor / probiotic-3 is [30]
  • bioflorin (deu) / bioflorin is [25]
  • miyarisan (jp) / miyarisan is [22]
  • Microbiome Labs / MEGA Genesis is [27]
  • Bulk Probiotics / L. Reuteri Probiotic Powder is [27]

Consensus View?

You can build consensus views, a.k.a. Monte Carlo model, but IMHO that is likely done by those that want to “over work the problem”.

Summary of Suggestions

Remember these are suggestions, and NOT a protocol. What you actually do should be reviewed by a knowledgeable medical professional before starting.

My own proposal for discussion would be:

This can be made more complex by using consensus / Monte Carlo Model

Reader Plan

Microbiome Prescription produces suggestions, the weights/priorities are the odds of causing a change and not the amount of change (there is simply no objective data to compute the amount). This reader did their own evaluation of what they felt comfortable with (excellent idea).

I have also bought 2 more tests so I will do them with max 3 months apart as you said in the video.

I came up with this protocol by using the “Beginner-Symptoms: Select bacteria connected with symptoms”:

  • Week 1-2: Gum arabic
  • Week 3-4: Monolarin (lauric acid)
  • Week 5-6: Psyllium
  • Week 7-8: Rosemary 
  • Week 9-10: Parsley
  • Week 11-12: SymbioFlor-2

I found that I get best results from herbs, prebiotics and antibiotics. The only probiotic I’ve got good results from is Symbioflor 2 (an E.Coli probiotic) [Editor: E.Coli probiotics also worked best for me]

A lot of probiotics that I’ve tested I’ve got bad results from. 

Postscript and Reminder

As a statistician with relevant degrees and professional memberships, I present data and statistical models for evaluation by medical professionals. I am not a licensed medical practitioner and must adhere to strict laws regarding the appearance of practicing medicine. My work focuses on academic models and scientific language, particularly statistics. I cannot provide direct medical advice or tell individuals what to take or avoid.My analyses aim to inform about items that statistically show better odds of improving the microbiome. All suggestions should be reviewed by a qualified medical professional before implementation. The information provided describes my logic and thinking and is not intended as personal medical advice. Always consult with your knowledgeable healthcare provider.

Implementation Strategies

  1. Rotate bacteria inhibitors (antibiotics, herbs, probiotics) every 1-2 weeks
  2. Some herbs/spices are compatible with probiotics (e.g., Wormwood with Bifidobacteria)
  3. Verify dosages against reliable sources or research studies, not commercial product labels. This Dosages page may help.
  4. There are 3 suppliers of probiotics that I prefer: Custom Probiotics , Maple Life Science™, Bulk Probiotics: see Probiotics post for why
  5. My preferred provider for herbs etc is Maple Life Science™ – they are all organic, fresh, without fillers, and very reasonably priced.

Professional Medical Review Recommended

Individual health conditions may make some suggestions inappropriate. Mind Mood Microbes outlines some of what her consultation service considers:
A comprehensive medical assessment should consider:

  • Terrain-related data
  • Signs of low stomach acid, pancreatic function, bile production, etc.
  • Detailed health history
  • Specific symptom characteristics (e.g., type and location of bloating)
  • Potential underlying conditions (e.g., H-pylori, carbohydrate digestion issues)
  • Individual susceptibility to specific probiotics
  • Nature of symptoms (e.g., headache type – pressure, cluster, or migraine)
  • Possible histamine issues
  • Colon acidity levels
  • SCFA production and acidification needs

A knowledgeable medical professional can help tailor recommendations to your specific health needs and conditions.

Microbiome Tests Obfuscation of the Microbiome

The cartoon below illustrates what 6 different microbiome testing companies report on a person’s microbiome. This is not talking about 6 different samples from a stool — but from a single FASTQ digital file from a stool. In other words, all of them got the identical digital data.

For background, see The taxonomy nightmare before Christmas….

There are parallels between Hans Christian Andersen’s “The Emperor’s New Clothes” and the certainty of correct identification of bacteria often expressed by many microbiome researchers should be noted. “Andersen altered the source tale to direct the focus on courtly [academic] pride and intellectual vanity “

Attached you will find a PowerPoint PDF with a YouTube presentation. The target is treating Medical Practitioners. Despite these issues, the microbiome test data can be very useful after some data manipulation and with a suitable reference data set.

Above is a detailed walk through targeted for Medical Practitioners on using the Microbiome to treat Long COVID and ME/CFS. New findings on strong associations (P less than 0.001) derived from the microbiome to these conditions. Discussion of how these finding can lead to treatment suggestions on an individual basis (instead of generic suggestions). Associations listed in full at:

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.