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 Enterococcus, Clostridium 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.

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 Based	Enzyme Based	Metabolite 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

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 [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?“

• Issues with blood flow, again many options
  • Inflammations of veins (click for more info) and blood vessel damage [NIH]
  • Decreased elasticity of red blood cells (click for more info) and similarly misshapen red blood cells
    • Higher percentages of misshaped red blood cells[13] [14] (2001) (other)
    • Significant decrease in red cell distribution width (2007)
  • Decreased blood volume “Circulating Blood Volume in Chronic Fatigue Syndrome [1998]”
  • “Studies have reported that COVID-19 patients had significantly more heterogeneous size and deformation of RBCs compared to healthy controls”[SARS-CoV-2 Altered Hemorheological and Hematological Parameters during One-Month Observation Period in Critically Ill COVID-19 Patients]
• Contributing factor: Small heart syndrome [2008] [2009] [2011] [2012] or heart damage [NCBI]
• Hemoglobin issues (Hemoglobin, a form of iron, is what carries oxygen). Some bacteria are iron greedy, reducing the iron available.
  • “Iron homeostasis disturbances may persist for more than two months after the onset of COVID-19, which may lead to reduced iron bioavailability, hypoferremia, hyperferritinemia, impaired hemoglobin, and red blood cell synthesis.” [2022]
  • “Research has shown that long COVID may be associated with low iron levels and anemia.”

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

• Lactobacillus acidophilus and Lactobacillus plantarum 299v: When added to iron-fortified milk, it significantly improved red blood cell and hemoglobin levels in anemic children compared to those who consumed iron-fortified milk without the probiotic. [Ameliorating effects of probiotics on alterations in iron homeostasis and inflammation in COVID-19]
• For more details, see this answer.

Coagulation

• Fibrinolytics – Dissolves old Coagulation
• Amyloids, brain fogs and possible treatment approaches.
• Following supplements can inhibit some forms of coagulation
  • Omega-3 Fatty Acids
  • Selenium
  • Magnesium
  • Resveratrol
  • Rutin
  • Ginkgo, ginseng, garlic, ginger, curcumin, salicylates (such as willow bark and aspirin), milk thistle, and jasmine.

Microbiome

• Coagulation Impact:
  • The intestinal microbiome potentially affects thrombin generation in human subjects [2020]
  • The gut microbiome and thromboembolism [2020]
  • The gut microbiota – a modulator of endothelial cell function and a contributing environmental factor to arterial thrombosis. [2019]
  • Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk. [2016]
    • Identifies: Anaerococcus hydrogenalis, Clostridium asparagiforme, Clostridium hathewayi, Clostridium sporagenes, Escherichia fergusonii, Proteus penneri, Providencia rettgeri, and Edwardsiella tarda

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.

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

• Use of probiotics in preventing and treating excess weight and obesity. A systematic review “the use of probiotics in the absence of dieting produced a significant reduction in body weight and body mass index in 66.6% of the reviewed studies”
• Akkermansia muciniphila Suppresses High-Fat Diet-Induced Obesity and Related Metabolic Disorders in Beagles.
• Effects of oral Akkermansia muciniphila supplementation in healthy dogs following antimicrobial administration.
• Akkermansia and Microbial Degradation of Mucus in Cats and Dogs: Implications to the Growing Worldwide Epidemic of Pet Obesity.
• The Role of Lactobacillus plantarum in Reducing Obesity and Inflammation: A Meta-Analysis. “The analysis of nine studies revealed significant weight reduction and BMI decreases with L. plantarum supplementation compared to a placebo”
• The Effect of the Lacticaseibacillus paracasei BEPC22 and Lactiplantibacillus plantarum BELP53 Combination (BN-202M) on Body Fat Percentage Loss in Overweight Individuals: A Randomized, Double-Blind, Placebo-Controlled Study. “Akkermansia showed a statistically significant with these probiotics”
• Lactobacillus paracaseiN1115 attenuates obesity in high-fat diet-induced obese mice.

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.

• A Critical Perspective on the Supplementation of Akkermansia muciniphila: Benefits and Harms.
  “Accumulating evidence indicated Akkermansia as a promising therapeutic probiotic against metabolic disorders such as obesity, type 2 diabetes and cardiovascular diseases.”

• Akkermansia muciniphila and Gut Immune System: A Good Friendship That Attenuates Inflammatory Bowel Disease, Obesity, and Diabetes.
• Review of Literature on Akkermansia muciniphila and its Possible Role in the Etiopathogenesis and Therapy of Type 2 Diabetes Mellitus.
• Molecular Mechanism of Pasteurized Akkermansia muciniphila in Alleviating Type 2 Diabetes Symptoms.
• Live and pasteurized Akkermansia muciniphila ameliorates diabetic cognitive impairment by modulating gut microbiota and metabolites in db/db mice.
• Akkermansia muciniphila: a potential candidate for ameliorating metabolic diseases.
• Function of Akkermansia muciniphila in type 2 diabetes and related diseases.
• Health and Disease: Akkermansia muciniphila, the Shining Star of the Gut Flora.
• [Research Progress on the Role of Akkermansia Muciniphila in Prevention and Treatment of Diabetes Mellitus].

And

• Ameliorative Effects of Lactobacillus paracasei L14 on Oxidative Stress and Gut Microbiota in Type 2 Diabetes Mellitus Rats.
• Anti-Diabetic Effect of Lactobacillus Paracasei Isolated from Malaysian Water Kefir Grains.
• Screening of Potential Probiotic Lactobacillaceae and Their Improvement of Type 2 Diabetes Mellitus by Promoting PI3K/AKT Signaling Pathway in db/db Mice.
  •  Lactiplantibacillus plantarum
  • Limosilactobacillus fermentum
• Heat-Killed Lactiplantibacillus plantarum LRCC5314 Mitigates the Effects of Stress-Related Type 2 Diabetes in Mice via Gut Microbiome Modulation.
• Effects of Lactobacillus plantarum supplementation on glucose and lipid metabolism in type 2 diabetes mellitus and prediabetes: A systematic review and meta-analysis of randomized controlled trials.
• Effect of postbiotic Lactiplantibacillus plantarum LRCC5314 supplemented in powdered milk on type 2 diabetes in mice.
• Lactobacillus paracaseiN1115 attenuates obesity in high-fat diet-induced obese mice.
• A Potential Synbiotic Strategy for the Prevention of Type 2 Diabetes: Lactobacillus paracasei JY062 and Exopolysaccharide Isolated from Lactobacillus plantarum JY039.

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).

• Akkermansia muciniphila
• Lactiplantibacillus plantarum aka Lactobacilllus plantarum
• Limosilactobacillus fermentum aka Lactobacilllus fermentum
• Lactobacillus Paracasei

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.

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]

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

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 Name	Percentage Of Conditions with Shifts
Bifidobacterium	55
Prevotella	54
Bacteroides	52
Faecalibacterium	51
Lactobacillus	47
Blautia	44
Ruminococcus	43
Streptococcus	41
Roseburia	40
Escherichia	40
Clostridium	38
Parabacteroides	37
Coprococcus	34
Alistipes	33
Eubacterium	31
Shigella	31
Veillonella	30
Akkermansia	29
Fusobacterium	27
Dorea	27
Enterococcus	27
Anaerostipes	26
Dialister	25
Collinsella	25
Haemophilus	25
Klebsiella	25
Odoribacter	25
Megamonas	23
Bilophila	22
Desulfovibrio	22
Subdoligranulum	22
Lachnospira	21
Turicibacter	21
Phascolarctobacterium	20
Eggerthella	20
Enterobacter	20
Butyricicoccus	18
Oscillibacter	18
Porphyromonas	18
Megasphaera	17
Lachnoclostridium	16
Sutterella	16
Staphylococcus	16
Butyricimonas	16
Actinomyces	16
Oscillospira	15
Romboutsia	14
Parasutterella	14
Barnesiella	14
Campylobacter	14
Anaerotruncus	14
Paraprevotella	14
Methanobrevibacter	14
Catenibacterium	13
Butyrivibrio	13
Flavonifractor	13
Citrobacter	13
Coprobacillus	12
Adlercreutzia	12
Parvimonas	12
Rothia	12
Pseudomonas	12
Acidaminococcus	11
Fusicatenibacter	11
Gemella	11
Corynebacterium	11
Agathobacter	11
Ruminiclostridium	11
Lactococcus	11
Weissella	11
Slackia	10
Alloprevotella	10
Eisenbergiella	10

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 Name	Direction of shift	Percentage
Actinomyces	H	13
Agathobacter	L	8
Akkermansia	H	21
Akkermansia	L	15
Alistipes	H	20
Alistipes	L	21
Anaerostipes	H	11
Anaerostipes	L	17
Anaerotruncus	H	11
Bacteroides	H	37
Bacteroides	L	37
Barnesiella	L	9
Bifidobacterium	H	32
Bifidobacterium	L	43
Bilophila	H	14
Bilophila	L	9
Blautia	H	28
Blautia	L	27
Butyricicoccus	L	16
Butyricimonas	H	8
Butyricimonas	L	10
Butyrivibrio	L	11
Campylobacter	H	13
Catenibacterium	H	8
Citrobacter	H	10
Clostridium	H	25
Clostridium	L	20
Collinsella	H	18
Collinsella	L	12
Coprobacillus	H	10
Coprococcus	H	15
Coprococcus	L	28
Corynebacterium	H	8
Desulfovibrio	H	18
Dialister	H	11
Dialister	L	18
Dorea	H	18
Dorea	L	15
Eggerthella	H	17
Enterobacter	H	14
Enterococcus	H	21
Enterococcus	L	13
Escherichia	H	37
Eubacterium	H	12
Eubacterium	L	26
Faecalibacterium	H	18
Faecalibacterium	L	44
Flavonifractor	H	12
Fusobacterium	H	22
Gordonibacter	H	8
Haemophilus	H	13
Haemophilus	L	15
Klebsiella	H	23
Lachnoclostridium	H	12
Lachnospira	L	14
Lactobacillus	H	28
Lactobacillus	L	31
Megamonas	H	14
Megamonas	L	14
Megasphaera	H	13
Methanobrevibacter	H	13
Neisseria	H	8
Odoribacter	H	17
Odoribacter	L	12
Oscillibacter	H	14
Oscillospira	H	11
Parabacteroides	H	29
Parabacteroides	L	16
Paraprevotella	H	8
Paraprevotella	L	8
Parasutterella	L	11
Parvimonas	H	8
Phascolarctobacterium	H	13
Phascolarctobacterium	L	13
Porphyromonas	H	14
Prevotella	H	40
Prevotella	L	36
Pseudomonas	H	9
Romboutsia	L	11
Roseburia	H	13
Roseburia	L	34
Rothia	H	11
Ruminococcus	H	27
Ruminococcus	L	25
Shigella	H	30
Staphylococcus	H	14
Streptococcus	H	36
Streptococcus	L	14
Subdoligranulum	H	11
Subdoligranulum	L	15
Sutterella	H	11
Sutterella	L	8
Turicibacter	H	11
Turicibacter	L	14
Veillonella	H	21
Veillonella	L	12

Where are the buttons to generate these?

• Just Give Me Suggestions

• Cross Validated Suggestions

Key Differences

Description	Just Give Me	Cross Validated
Bacteria Considered	All bacteria	Only bacteria associated with condition from Pub Med Studies
Suggestions	All Modifiers	Only modifiers reported to help at least one of the conditions from Pub Med Studies
Priority	Weight given	No ranking, all are both agree without ranking
Target Audience	Microbiome educated Medical types	Conservative Medical Type that are not familiar with the microbiome and recent research.
Condition Citations	No condition citations included	Most available condition citations for bacteria shift and suggestions are listed on one page with hyperlinks.
Microbiome Citations	All are available by individual links.	Only a token number of citations on how suggestions modify bacteria (why? full list can be massive)
Algorithm	Monte Carlo Model with multiple algorithms	Single Algorithm using above 85%ile and below 15%ile as bacteria selection criteria
Goal	Best suggestions based on the art of the microbiome	Educating and getting buy-in with conventional MDs
Special Goals	Focus on the holistic microbiome independent of specific diagnosis	Help MD pick the best for the microbiome choice from possible pro-forma treatments.

A possible example: the MD wants to prescribe an antibiotics for a condition. Usually, there are a half dozen possible choices. Ideally, the MD will be willing to go with the one that is best for the microbiome when shown the evidence from the computations.

Which is best?

The Cross-Validated has a limited list because it is very time consuming to populate the data needed for it. For items like biofilm, d-lactic acid and histamine — it is likely the best choice but the suggestions should be checked with the “Just give me suggestions” and the final suggestions should be only ones that both agree with — subject to review by your medical professional.