Month: June 2024

Example of how to research

A person asked:

Should I be taking flushing niacin with Crohn’s Disease. I feel better after taking it, but I read that it encourages the release of prostaglandins, particularly prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2), rather than histamine.

My first step is to go to Perplexity.AI and ask questions there and then check the sources cited. I then use this to jump into PubMed to get better information. As with all AI, you need to learn to ask clear specific questions.

Questions:

  1. What are the consequences of using flushing niacin with Crohn’s Disease?
  • After reading the studies, I go to the PubMed Summary and look at Similar articles and Cited By. Often this will lead to other studies.
  • Next I return to Perplexity and look at the follow up questions that it proposes.
  • The process is repeated — every item to be consider should check the source study.

The next step is take all of the key words above and do a full text search on PMC

  • Crohn’s Disease
  • Niacin
  • prostaglandin D2 (PGD2)
  • D prostanoid receptor 1 (DP1)
  • inflammation. 

For words that you are not familiar with, just ask Perplexity.

  • “What is the role of D prostanoid receptor 1 (DP1).”
    • Full Answer.
    • Follow up Question (asking the question from a different direction) “What is its impact on Crohn’s disease”

Searching PMC

Just go to the site: https://www.ncbi.nlm.nih.gov/pmc/

  • Entering: Niacin and inflammation => 12,000 hits
    • Changing to: Niacin inflammation Crohn’s => 1127 hits

I changed to default order (most relevant first) and spotted some interesting titles:

This study was of particular interest: Identifying metabolic shifts in Crohn’s disease using ‘omics-driven contextualized computational metabolic network models [2023]

“Interestingly, high-dose vitamin B3 treatment has been shown to ameliorate ulcerative colitis through increased prostaglandin D2 synthesis in mice54. Thus, niacin supplementation can be a potential therapeutic target to be investigated in CD as well. In addition, untargeted metabolomics showed the dysregulation of pathways related to pyrimidine, glutamate, and nitrogen metabolism. “

Second Question: Niacin and MCAS

Mast cell activation syndrome (MCAS) is another issue that the person is dealing with.

Asking more we get a yes/no with lacking studies.

Digging more we see other things that are EITHER/OR. Thus PGD2 in isolation is not connected to activation; rather activation is conditional on multiple factors (one of them is PGD2). “MCAS is associated with a variety of mediators beyond PGD2, including histamine, tryptase, leukotrienes, cytokines, heparin, PAF, neuropeptides, and other eicosanoids.”

  • “Tests for serum PGD2 have similar drawbacks, as processing of peripheral blood samples can trigger non-MC cellular elements to release PGD2; ingestion of niacin is also associated with elevations in serum PGD2 ” [1994] so this may rendering test results invalid.
  • Using the Right Criteria for MCAS [2023]
    • “Mediators other than tryptase, including urinary metabolites of histamine, prostaglandin D2 (PGD2), and leukotrienes, are also available but less specific for MCs and MCAS [28, 29, 30••]. Additionally, the sensitivity and specificity of these markers have not been determined, nor have the reliable indicators of systemic MC activation, such as significant increase and cut-off levels. ‘
    • “PGD2, while primarily released by MC, is also produced by other immune and nonimmune cell types [42–45]..elevations in PGD2 might be due to a pathologic process independent of MC activation.”
  • Concentrating on Niacin and Histamine, Perplexity gives plus and minus, concluding “In summary, niacin can both positively and negatively impact histamine levels and symptoms.” So, our bottom line is that it depends on the individual.

The responses mention S-adenosylmethionine (SAMe) being consumed with Niacin.

Which implies SAMe should be taken with the Niacin.

Bottom Line

The final decision is always the person in consultation with their medical professional. Using Niacin as a treatment for Crohn’s Disease is heading for clinical trial and suggested by a 2023 metabolic shifts study on Crohn’s. Given the low risk (assuming medical monitoring for niacin risk), I personally would favor doing it (making sure their usual MD is aware of the dosage and a possible need to monitor).

The purpose of this post is to show a method of gathering information to make better health choices. I have fallen in love with Perplexity.AI because it cites studies on PubMed often and it’s suggestions are easy to verify and evaluate. It also prompts for follow up questions.

We discovered a multitude of deficiencies that may need to be supplemented (factoring in poor absorption due to Crohn’s) including:

  • SAMe (because of the niacin use)
  • fructose,
  • poly-unsaturated fatty acids,
  • omega-3 fatty acids,
  • vitamin E and C,
  • thiamine,
  • niacin,
  • pyridoxine,
  • Mg,
  • P,
  • Iron,
  • Copper,
  • Zinc

This lead to the logic questions: What are all the deficiencies seen in Crohn’s disease that can be supplemented? Full Answer.

P.S. The time it took to do the above was about 90 minutes,

Probiotics — what is advertised may not be what you get

Over the years, I ended up with some simple rules for what I will buy. The rules are simple:

  • Trademarked/copyrighted/patented species, ideally ones with some research. All of them are listed on this page with links to the research. Ideally, just the one researched for your conditon.
  • Single species with (almost) no fillers. There are precisely three sources that I use:
    • Custom Probiotics :they list all of their strains — many are researched on the above list
    • Maple Life Science™: No strains yet, but shipments usually have manufactured date within 4 weeks of arrival (i.e. FRESH).
    • Bulk Probiotics: US based Newbie — but has some species not available at the other two sites. Specifically, Lactobacillus Jensenii that has great potential for Crohn’s disease.
  • NOTE: none of these sell retail, single source for purchase. This keeps their costs down and their product fresh.

Personal Experience

This family experience with all of the single strain probiotics has been:

  • If we have not used before, we notice changes within 1-3 days in stools, symptoms, etc. These may not always be desired symptoms (i.e. one probiotic before bed, kept us awake all night; other probiotics give us deeper and longer sleep than normal). In some cases, changes are observed within 60 minutes. Changes of stools are a common change.
  • We usually do one new probiotic at a time for 2 weeks to get “a feel” for what it does
  • We constantly rotate – never more than 1 month on any probiotic “It has done what it is going to do“

“If there is no changes, the probiotic is dead, Jim” or not of benefit to you. Move on. A common observation that we saw using most probiotics purchased from local stores.

Medical Claims

I do not trust any claims on the bottle

The outcome of the first series of health claim applications for probiotics in Europe as evaluated by the European Food Safety Authority (EFSA) has, up to 2013 almost completely yielded negative results. All recent applications also have been rejected, including the latest on prevention of mastitis in breastfeeding mothers. 

The ascent of the blessed: regulatory issues on health effects and health claims for probiotics in Europe and the rest of the world [2018]

I don’t trust retail mixtures with good reasons:

  • Assessment of commercial probiotic bacterial contents and label accuracy [2011]
    • Misspelled organisms: 32% — using outdated names higher!
    • Just 27% of claims of viable organisms met or exceeded their label claim
  • Evaluation of deficiencies in labeling of commercial probiotics [2003]
    • Misspelled organisms: 25%
    • Bacterial species were misidentified 35-43% of the time
    • Misidentifications included stating a name that had been changed
      • i.e. “Streptococcus faecium” and not Enterococcus faecium
      • Non existent species: “Lactospore sporogenes“
  • Identification and antibiotic resistance of isolates from probiotic products. Abstracts of 101st ASM General Meeting. The American Society for Microbiology, Washington DC, USA,
    • for 30 dried probiotic supplements tested,
    • 11 contained no viable bacteria,
    • only 7 contained all claimed species
    • 18 had species other than those on-label.
  • Deficiencies in microbiological quality and labelling of probiotic supplements [2002]
    • 63% of the UK products tested were below standard.
    • Enterococcus faecium (not stated on label) and was labelled with the misleadingand invalid name ‘‘L. bifidus’’.
  • Microbiological Quality and Antimicrobial Resistance of Commercial Probiotic Products for Food-Producing Animals [2024]
    • 64.4% were incorrectly labeled in either number of viable cells or bacterial species
    • 51.6% exhibited resistance to at least one antimicrobial agent
    • 26.8% had a lower number of viable cells than their label claims, No viable Lactobacillus was found in some products 
    • 57.8% comprised other species rather than those claimed on the contents
  • More Information Needed on Probiotic Supplement Product Labels [2019]
    • This cites this as the minimum recommended standard.
      • Genus and species names, which should adhere to current scientifically valid nomenclature.
      • Strain designations for each strain in the product. Designations used should enable tracking of the strain to entries in strain depositories and linking to published studies.
      • Statement of quantity (using CFU or other validated measure) of live/active microorganisms through the use-by date.
      • Use-by date.
      • Statement of benefit is not required, but if present must be supported by a human study showing the benefit at the dose delivered in the product.
      • Proper storage conditions Required.
      • Company contact information.
    • Warns of genetic drift (bacteria mutations) and cites the popular
      • L. rhamnosus (GG) that exhibited multiple genotypes in consumer products (Sybesma et al., 2013). So the bottom of LGG you buy may not be the same strain as the studies used.
  • Improving End-User Trust in the Quality of Commercial Probiotic Products [2019] shows the evidence issue, manufacturer will toss the kitchen sink into a blend and make questionable claims to promote sales.

Custom Probiotic Strains

I have the following information on Custom Probiotics strains on my CFS Remission Site and reposting here so people can find them faster.

  • B. Lactis, Strain BL-04
  • B. Bifidum, Strain Bb-06
  • B. Breve Probiotic Powder, Strain BB-18
  • B. Infantis, Strain Bi-26
  • B. Longum, Strain BL-05
  • L. Acidophilus, Strain LA-14
  • L. Brevis, Strain LBR-35
  • L. Bulgaricus Probiotic Powder, Strain LB-87
  • L. Casei Probiotic Powder, Strain LC-11
  • L. Fermentum Probiotic Powder, Strain SBS-1
  • L. Gasseri Probiotic Powder, Strain LG-36
  • L. Paracasei Probiotic Powder, Strain LPC-37
  • L. Plantarum, Strain LP-115
  • L. Reuteri Probiotic Powder, Strain UALre-16
  • L. Rhamnosus Powder, Strain LR-32
  • L. Rhamnosus Probiotic Powder, Strain GG
  • L. Salivarius, Strain LS-33
  • S. Thermophilus Probiotic Powder, Strain ST-21

Some of these have studies, see the researched list.

Revisiting Excess Histamine or Insufficient DAO

Today, I looked at the bacteria associated to histamine conditions and found the quality of research lacking. I had imported a lot of data from Alison Vickery web site. Unfortunately some of the bacteria cited as producing histamines according to Kyoto Encyclopedia of Genes and Genomics lack the enzymes to produce histamine. Today, I spent the morning checking published studies on the US National Library of Medicine to see if there is any evidence of histamine production there — little luck. As a result, I deleted the data since it was not at the desired quality.

Quick Summary

  • It is strongly recommended that the sources be read before taking any actions
  • Items that may help:
    • DAO
    • Anti-Histamines
    • HNMT histamine N-methyltransferase (prescription)- is possible help
  • Items to Avoid:
    • Vitamin B1
    • Vitamin C
    • Histamine Liberators [2015] – Many of these items have zero histamine (research is sparse)
      • Tomatoes, eggplant, spinach, fish, chicken and every stored meat. All fermented food (cheeses, sausages, sauerkraut, wine, beer, champagne …
      • Pineapple, bananas, citrus fruits, strawberries, nuts, papaya, tomatoes, liquorice, spices, legumes, cocoa [2021] [2005], alcohol; fish, seafood, pork, egg white
      • MECHANISM: “The presence of putrescine, which may interfere with histamine degradation by the DAO enzyme at the intestinal level, could partly explain the reason why certain foods (i.e., citrus fruits and bananas) were also frequently reported in low-histamine diets” [2021] This link has a table showing the amount in various foods.
      • In Medicine:
        • Painkillers (morphine, pethidine, codeine, metamizole, antiflogistics (acetylsalicylic acid), antibiotics (d-cycloserine, chloroquin, pentamidine), anti-hypotensives (dobutamine), antihypertensive drugs (verapamil, alprenolol), antitussives (codeine), cytostatics (cyclophosphamide), diuretics (amilorid), iodine-containing contrast medium, local anaesthetics (mesocaine, procaine, marcaine, prilocaine), muscle relaxant (d-tubocurarin), narcotics – anaesthetics (barbiturates, thiopental) Painkillers – antipyretics (acetylsalicylic acid, diclofenac, flurbiprofen, indomethacin, ketoprofen, mefenamin, naproxen…) 
    • DAO Reducers:
      • Antiarrhythmics (verapamil, propafenone), antibiotics (cefuroxime, cefotiame, acidum clavulanicum, doxycyclinum, isoniazid, framycetin), painkillers (metamizole), antidepressants, psychiatric medication (amitriptiline, diazepam, inhibitors MAO–1, haloperidol), antiemetics (metoclopramide), antihistamines (promethazine, cimetidine), antihypertensive drugs (dihydralazine), antimalarials (chloroquin), bronchodilators (aminophylline, theophylline), diuretics (furosemide), mucolytics (N-acetylcysteine, ambroxol), muscle relaxant (alcuronium, pancuronium, d-tubocurarin), antiseptics (acriflavinium chloride), chinidin 
    • Aspirin (Acetylsalicylic acid)
    • NAC (N-Acetylcysteine) aka Acetylcysteine
    • L-Glutamine [2022]
    • Nonsteroidal anti-inflammatory drugs
      • ibuprofen.
      • naproxen.
      • diclofenac.
      • celecoxib.
      • mefenamic acid.
      • etoricoxib.
      • indomethacin.

See below for detail

From Low-Histamine Diets: Is the Exclusion of Foods Justified by Their Histamine Content? [2021]

The PDF below is from the Swiss Interest Group Histamine Intolerance (SIGHI) food list that appears to be awesome! They also have a smart phone application.

21_FoodList_EN_alphabetic_withCategDownload

Analysis and Research

This post is the next step — checking the latest literature and summarizing it in this post. I jump started by using Perplexity.

  • Genetic Factors
    • “An increased risk for migraines was demonstrated in patients with some DAO genotypes and allelic variants” [2015]
      • “A high incidence of DAO deficiency at nearly 90% was observed in migraine patients [2018]
      • “a study demonstrated that oral ingestion of capsules with DAO significantly reduces headaches in migraine patients” [2018]
    • Genetic mutations that result in lower production or impaired function of the DAO enzyme, which breaks down histamine.
      • SNP: Amine Oxidase Copper Containing 1 (AOC1) [2023]
      • rs2052129 (minor allele T)  [2011][2024]
      • rs2268999 (minor allele T) [2011][2024]
      • rs10156191 (minor allele T) [2011][2024] 
      • rs1049742 (minor allele T) [2011][2024]
      • rs1049793 (minor allele G) [2011][2024] 
      • rs1050891 (C314T polymorphism) with the minor T allele [2010]
      • Gastrointestinal Disorders
  • Medications: Certain medications like antibiotics, antidepressants, antiarrhythmics, muscle relaxants, and NSAIDs can inhibit DAO activity or block histamine breakdown. Table below is from a [2021] article.
MedicationsGeneric Name
AnalgesicsAcetylsalicylic acid, Metamizole, Morphines, Nonsteroidal anti-inflammatory drugs, Pethidine
AntiarrhythmicsPropafenon
AntibioticsCefuroxime, Cefotiam, Isoniazid, Pentamidine, Clavulanic acid, Chloroquine
AntidepressantsAmitriptylline
AntifungalPentamidine
AntihypertensivesVerapamil, Alprenolol, Dihydralazine
AntihypotensivesDobutamine
AntimalarialChloroquine
BroncholyticsAminophylline
CytostaticsCyclophosphamide
DiureticsAmiloride
H2 receptor antagonistsCimetidine
Local anestheticsPrilocaine
Motility agentsMetoclopramide
MucolyticsAcetylcysteine, Ambroxol
Muscle relaxantsPancuronium, Alcuronium, D-Tubocurarin
NarcoticsThiopental
VitaminsAscorbic acid (Vitamin C), Thiamine (Vitamin B1)
  • Diet: Consuming foods rich in histamine (aged cheese, fermented foods, alcohol, etc.) can overwhelm the body’s ability to break down histamine, leading to an accumulation.
  • Perplexity AI suggested: “Conditions like inflammatory bowel disease (IBD), leaky gut syndrome, and other gastrointestinal disorders can impair DAO production and histamine breakdown.” Unfortunately it’s sources were poor. Checking PubMed, we see the following studies indicate that it appears to apply possibly apply only to one type of IBS.
    • “DAO levels were significantly higher in Crohn’s patients with the active stage compared to controls.” [2019]
    • “histamine levels were normal in CD and UC.” [2015]
    • “subjects with irritable bowel syndrome[IBS] could be discriminated from healthy controls using their metabolic fingerprints… Levels of some urinary metabolites including histamine correlated significantly with irritable bowel syndrome symptom severity scores.” [2019]
    • “The mast cells’ histamine release appears linked to GI-involving diseases like celiac disease (CD), eosinophilic gastroenteritis (EGE), and mast cell activation syndrome (MCAS) “[2020]

The above chart from Noninvasive biomarkers of gut barrier function identify two subtypes of patients suffering from diarrhoea predominant-IBS: a case-control study [2018] shows there is not a reduction of DAO with IBS, and an increase with Crohn’s Disease (as cited in another study above). When IBS was decomposed by type, one was below the controls and the other was above the controls (same level as CD).

  • Intestinal barrier dysfunction: Impaired intestinal barrier function (leaky gut) can allow increased absorption of histamine from the gut into the bloodstream, contributing to histamine overload.
    • No clear strong evidence found, a reasonable speculation
    • But evidence of bacteria shifts:
      • Reduced Bifidobacteriaceae (Bifidobacterium), Butyricimonas, and Hespellia (P = 0.025); Roseburia increased [2018]
      • Reduced Prevotellaceae, Ruminococcus, Faecalibacterium and Faecablibacterium prausnitzii [2022],
  • Bacterial overgrowth: An overgrowth of certain bacteria in the gut can lead to excessive production of histamine, overwhelming the DAO enzyme’s capacity to break it down
    • “a significantly higher abundance of histamine-secreting bacteria, including the genera Staphylococcus and Proteus, several unidentified genera belonging to the family Enterobacteriaceae and the species Clostridium perfringens and Enterococcus faecalis” [2022]

Probiotics

For a list of studies, click here. The following has some evidence of reducing histamines

  • Bifidobacterium bifidum
  • Bifidobacterium lactis
  • Enterococcus faecium
  • Lactobacillus casei Shirota
  • Lactobacillus paracasei 
  • Lactobacillus reuteri
  • Lactobacillus rhamnosus GG & GR-1
  • Mutaflor (Escherichia coli strain Nissle 1917)

Caution should be taken because one strain may produce histamine and another reduces it. The chart below show different strain of Lactobacillus reuteri. Some produces histamine and others do not. Bifidobacterium are in general safe. Lactobacillus has risks — if you try them, do one at a time when you are stable. Remember most probiotics are sold by Species and not Strain; same species from two different manufacturers may be different strains — so how lucky do you feel.

From prediction to function using evolutionary genomics: human-specific ecotypes of Lactobacillusreuteri have diverse probiotic functions[2014].

Your level of Histamine Producers in your Gut

This is now on Microbiome Prescription and is based on the count of species known to produce histamine in your sample.

Histamine N-methyltransferase 

A reader asked about this item that I missed.

Histamine N-methyltransferase (HNMT) is an enzyme that plays a crucial role in the inactivation of histamine in central nervous system, kidneys and bronchi. Inhibition of HNMT is known to have a potential role in treating attention-deficit hyperactivity disorder, memory impairment, mental illness and neurodegenerative illnesses.

Molecular docking studies of Nigella sativa L and Curcuma xanthorrhiza Roxb secondary metabolites against histamine N-methyltransferase with their ADMET prediction [2021]

Genetic polymorphisms in histamine-related genes, including FcεRI and HNMT, were suggested to be involved in mast cell activation and histamine metabolism. Several genetic polymorphisms of leukotriene-related genes, such as ALOX5, LTC4S, and the PGE2 receptor gene PTGER4, were suggested to be involved in leukotriene overproduction, a pathogenic mechanism. 

Molecular genetic mechanisms of chronic urticaria [2013]

From Drug Repurposing to Inhibit Histamine N-Methyl Transferase[2023] we have this chart suggesting that Metoprine is the best performing of the drugs tested.

There is a sparseness of explicit studies, but it may be worth discussing with your MD who is better able to evaluate the literature.

Report Targeted to MD in Multiple Languages

A common complaint that I have heard is a lack of knowledge about the microbiome by treating MDs. This issue is compounded by MDs allowing only 10-15 minutes appointments. Many of complaints are from EU Countries where their MD have limited mastery of English.

This reported is targeted for those MDs using the following strategy:

  • A short section of what should be substances should be tried to be reviewed by the MD.
    • Every item is linked to one or more studies where it was found helpful for some people (responders)
    • Every item is linked to the bacteria that it changes
  • A break down of all bacteria out of range according to studies on this condition, with links.
  • A detail cross reference on the bacteria that each substances. The goal is to encourage MDs to insure at least one substance is advocated for each bacteria
  • A long list of the studies cited. This list is intended to overwhelm the MD with evidence. One or two studies is easy to dismiss for many MDs. A long list is hard to dismiss psychologically..

How do I get this Report?

Assuming you have transfer or uploaded a sample to Microbiome Prescription, go to the [Changing Microbiome] tab. You will see your samples (and the active one). Below it is this section:

Pick the preferred language. Click the conditions you have. Click Get Report. If your condition is missing, see the bottom of this post for why and how you can change this.

How this Report is different

This uses a strictly “by the medical book” analysis and will likely generate some suggestions different from other reports on the site. This is required to be able to do cross references for every item.

Typical Knowledge Section

This is actually coming from ChatGPT and is a likely match to the MD’s “common sense”

Bacteria Being Targeted

This is next because we want to explain WHY we are making suggestions before presenting them.

Substances to Consider

This list may be long or short (depending on conditions). Many MDs will likely be happy with most of these suggestions. For those that they are unsure about, we have a link to studies that may persuade them over time.

Substance Impact on Bacteria

This is intended for MD education. It illustrates that the microbiome can be manipulated and there are lots of studies.

Additional Suggestions

This is intended to be a carrot for the MD to learn more.

References

This speaks for itself, and that the suggestions are well researched.

Why is your Condition not listed?

The simple reason is that someone has to diligently go through the literature to assemble all of the information by hand. Often a report will have more than 600 citations – that’s a lot of work. For Autism, some parents did the work and this we have a report for autism. If you are interested in doing this research for your missed condition(s) see Help Needed to Improve Suggestions for Autism. for the steps needed.

Just Identifying the Bacteria for more conditions….

Bottom Line

This report was engineered by trying to walk in the mind frame and world of the MD. Speak to him in his preferred language and way of thinking.

Enhancement: Amount of Biofilm Bacteria

A reader in Europe asked about this. I know it is a popular topic. So, I searched PubMed for the known biofilm forming bacteria and will be adding percentile ranking by labs in the coming days.

Raw Count Chart

As you can see below — a lot of people have ZERO of these bacteria. Other people may have 25% of their microbiome containing them. IMHO, influencers have seized on this concept as a “boogey man” for every one; it is not.

Transforming the data to get a Kaltoft-Moldrup estimator of the point of concern, we get a count of 565/million or 0.0565% being the threshold that action is strongly suggested. That is, with 85% of samples, it does not appear to be a significant issue. For 15%, it is

Stay tune. It will be added to the health analysis page with suggestions annotated with possible biofilm breakers for people exceeding 80%ile.

ME/CFS post EBV

Back story

I have a longstanding history with ME/CFS from 2006 – diagnosed with EBV at the time

The primary concerns are: fatigue, PEM, brain fog, exacerbation of symptoms prior to menstrual cycle (PMDD), ADHD, POTS (improving), anxiety, PCOS. The fatigue and PEM is the main concern. Many other symptoms recently improved. 

I’m currently taking L. rhamnosus, D-ribose, methylated B-complex, berberine, maitake, magnesium citrate, copper niacin and started myo-inositol after submitting the sample. I was also taking saccharomyces boulardii for weeks leading up to the sample collection. I’ve discontinued it since then. I would like to change my diet in general, but first want to see what’s recommended. Also particularly unsure about oxalates and whether or not to continue the maitake mushroom.
I’m also curious to try oxaloacetate,

Interestingly enough, I had rather extreme vaginal discharge and discomfort for many months, which completely went away within a couple of weeks of using a probiotic mix. I stopped this probiotic (it had 7 strains, I believe) and the discharge has not returned, although fatigue is worse (but other things also changed).

Analysis

The graphic overview is shown below. There are clearly a group of bacteria that are overgrown (70-89%ile) and other bacteria that rarely have token representations (0 -29%ile). This does not identify the bacteria but identifies misrepresentations (thus dysbiosis)

Looking at General Health Predictors, we see 12 items of concern, higher than seen in most reviews. Both Oxalate degrading and Oxalate producing at below 1%ile. Dr. Jason Hawrelak criteria came in at 78%ile

We have quite a number of bacteria strongly statistically associated symptoms and others associated with with health risks.

Going Forward

Where there are many issues wrong, I do not attempt to work bacteria by bacteria — instead, I trust the expert system to consider and balance all of the factors in a consistent and logical method. This is especially with the revised algorithm (see Algorithm for “Just Give Me Suggestions” with symptoms) . It inherited included items that in the past I have done as extra suggestions.

I have recently added new option to make the analysis simpler.

Items to Take

Today, I am working on several other posts from ME/CFS and the suggestions here are very similar to those suggestions (just different orders). Spices and herbs can be done as capsules, teas, oils or just putting on food.

Modifier To Take
whey
whole-grain barley
oregano (origanum vulgare, oil)
clostridium butyricum (probiotics),Miya,Miyarisan
syzygium aromaticum (clove)
thyme (thymol, thyme oil)
rosa rugosa
lactobacillus kefiri (NOT KEFIR)
lactobacillus paracasei (probiotics)
galla rhois
neem
garlic (allium sativum)
bifidobacterium animalis lactis (probiotics)
bifidobacterium infantis,(probiotics)
Shen Ling Bai Zhu San
lactobacillus casei (probiotics)
foeniculum vulgare,fennel
momordia charantia(bitter melon, karela, balsam pear, or bitter gourd)
triphala
mastic gum (prebiotic)
vitamin b2,Riboflavin
aloe vera
sucralose
soy

Looking at probiotics, we have a good number that would allow easy rotation of probiotics. Two are usually difficult to obtain: lactobacillus kefiri and lactobacillus sakei . Most are available at my usual two preferred sources: Custom Probiotics and Indian Bulk Exporter (Maple Life Sources). See this list for sources not available there. By rotation, I mean 20-50 BCFU daily of one probiotic for 2 weeks and then change to another probiotic.

lactobacillus kefiri (NOT KEFIR)
lactobacillus casei (probiotics) [CB,MLS]
lactobacillus sakei (probiotics)
bifidobacterium animalis lactis (probiotics) [CB,MLS]
lactobacillus reuteri (probiotics) [CB,MLS]
bifidobacterium infantis,(probiotics) [CB,MLS]
enterococcus faecium (probiotic)
lactobacillus paracasei (probiotics) [CB,MLS]
clostridium butyricum (probiotics),Miya,Miyarisan

Items to Avoid

Modifiers To Avoid
Slippery Elm
non-starch polysaccharides
xylan (prebiotic)
levan
l-citrulline
berberine
schisandra chinensis(magnolia berry or five-flavor-fruit)
low-fat diets
blackcurrant
symbioflor 2 e.coli probiotics
red wine
alcoholic beverages
animal-based diet
stevia
red alga Laurencia tristicha
high sugar diet
  • proton-pump inhibitors (prescription)

Suggestions look very “old-school ME/CFS”

By old school, I mean what was reported to help most people on the ancient egroup list CFSFMExperimental. Namely:

  • Whey (non-denatured was thought the best)
  • B-Vitamins
  • Bidifobacteria probiotics (little Lactobacillus)

For all items, I would suggest checking for sufficient therapeutic dosages here. The dosages on bottoms usually are maintenance and insufficient to be therapeutic. Example: Neem at 120mg/day which is 3 “00” capsules per day (just measured it!). Garlic is 4 grams per day – typically 4 commercial 1000mg capsules per day (double or more of the dosages on bottles). As you can see below, recommended dosages may be just 1/3 of that.

My general rule of thumb is 1 “00” capsule with each meal for most herbs. We make our own capsules using organic powders without fillers. Cheaper and better quality than commercial pills.

Remember, with herbs and probiotics you do not want to take the same one continuously. Take each set for 1-2 weeks and then rotate to another. For example

You should check each to see if they have adverse effect on whatever probiotics you may take concurrently. For example Shen Ling Bai Zhu San and rosa rugosa both are reported to increase Bifidobacterium — so taking Bifidobacterium with them is fine.

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.

Why sites suggestions disagree on the same data

A reader wrote:

There’s one thing I which caused some bewilderment though,  I put the screenshots from the recommendations from Biomesight here below, and I don’t understand why they seem quite divergent to what you are suggesting. I don’t know if it’s just my amateur eyes and then not so divergent after all, but to me they do seem quite different (apart from the lactobacilli). Shall I just ignore their suggestions ( also food wise) or would you say by and large it goes into the right direction? 

Reader, May 23,2024

The answer depends on the logic each provider uses, which bacteria are in their microscope that needs changes, depth of their research and their skills in addressing contradictory results. I will look at three providers below:

  • Biomesight (provided by the reader)
  • Vitract (from a review copy)
  • Microbiome Prescription

See also this post: Why do metabolite levels disagree between sites?

Biomesight

We see a number by each suggestion

Hovering over the item will show the bacteria believed to be impacted

Clicking on the name will show details. Note that the bacteria shown is correct. The link also shows “Galactooligosaccharides (GOS)” and not the food suggested explicitly. The food selected contains GOS but none of the studies are explicitly for Beetroot. To MP, the beetroot contains multiple compounds, some may have overpowering negative effects — hence MP keeps to precisely what is cited in the study.

My inferred take-away from looking at the suggestions

  • Foods and substances are done by association and inference
  • Only a handful of bacteria are considered.

Consider the bacteria list on MP for the same substance – 1757 citations at the moment.

Vitract

This is from an early draft. They are using the database of Microbiome Prescription but with a set of proprietary rules and algorithms. For the bacteria in their scope, MP has no contraindicated data and do not use inferences to parent or child taxa. That is, there is no need for balance algorithms. In short, it is a proprietary suggestion system designed by a Ph.D. in Molecular Genetics with a number of M.Sc. (for example, Bioinformatics) and Ph.D. Candidates (Nutrition), in consultation with MDs, NDs and Dieticians.

Microbiome Prescription

For details on which bacteria are selected, see Algorithm for “Just Give Me Suggestions”. Typically we have an average of 65 bacteria under our microscope with 600 on some shotgun samples. Roughly 20-30% of the bacteria identified.

Now for every suggestion we make available the list of studies (137 for this probiotic suggestion). Note in the study names — that this probiotic is explicitly named.

We also include the negative effects

We have our own proprietary algorithm on how to evaluate this data. People can take this data and apply their own logic.

MP’s goal is to be the most comprehensive source with new studies adding every week. We have also been delighted that Vitract (who I have been doing pro-bono consultation with) have set a team of their M.Sc. (or higher) staff on checking the citations. They have been finding a very low bad entry rate ( < 1%).

Bottom Line

  • What is the scope of their microbiome scope? IMHO: the bigger the scope, the better the results
  • Is the data based on explicit studies or on interference (A contain X and X helps — we’ll ignore B,C,D that is also in X)
    • BEWARE of sites that do not provide explicit studies – often they are working from hearsay.
  • Does the suggestion consider contraindicated information?
  • How big a database are they using? Have there been third party checking of the database?

Suggestions may be reasonable: a professional dietician would likely do the same logic in the case of BiomeSight suggestions.

Questions

  • Since Vitract and Microbiome Prescription use the same database, will suggestions always agree?
    • No, for several reasons:
      • The bacteria in-scope-to-change are different. If MP picks one that Vitract does not, then suggestions may shift for some substances. Vitract computes its own definitions of what is high and low.
      • Vitract hand select certain studies to be excluded or lessen in values. Studies may be on human, animals or a lab situation (petri dish) – they wanted to weight the value of each study different from MP.
  • What should I do if there are explicit disagreements?
    • The safest path is to do only things that there is agreement on.
    • If another item interests you, review the studies cited to make a decision.

Multiple COVID Infections… ouch

Backstory

I had no gut problems and only minor health niggles before Covid. I have been hypothyroid for 20 years.

After three rounds of covid (but no vaccines) I have burning and tingling parasthesias in my extremities, neuropathy in my face, plus gut pain, lots of hair loss, and I feel cold a lot and sleep poorly. Some fatigue and shortness of breath, but the other symptoms are much worse.

Trying to increase my bifido and lactobacillus via suggestions on biomesight has barely moved the needle.

All my blood tests work has been normal from a year ago, although now I have a weakly postiive ANA test result.

Analysis

We have 2 samples: 2023-11-20 and 2024-04-26. Both samples are very similar.

High Level Overview

Looking at the “smoking gun”, Pedobacter, we found no known factors to reduce it 🙁

Quick Summary; Past action plan has “barely moved the needle.”

Going Forward

The usual “just give me suggestions” with one addition Bifido and lactobacillus are her primary concern, so I will hand picked those on both samples. and get an emphasis for thoses. We see that one went up and one went down.

Bacteria20242023
Lactobacillus (only Lactobacillus iners)38%ileNONE
Bifidobacterium8%ile39%ile

We then do a Uber Consensus with BOTH samples (since they are similar) with a total of 11 sets of suggestions.

  • All 11 agrees on these:
    • bifidobacterium animalis lactis (probiotics)
    • vitamin a
    • Olive Oil
    • barley
    • lactobacillus brevis (probiotics)
    • clostridium butyricum (probiotics),Miya,Miyarisan
    • ginger and rosemary
  • Items to be avoided on all 11 are below
    • lactobacillus gasseri (probiotics)
    • chitosan,(sugar)
    • vegetarians
    • blackcurrant
    • Dextrin
    • Guaiacol (polyphenol)

I looked at the interaction charts, the first one is for Lactobacillus and noticed high (99%ile) for Rickettsia and for Heliobacter (61%ile). The last one suggests testing for Helicobacter pylori should be discussed with their MD.

The chart for bifidobacterium shows many of the same bacteria that will surpress bifidobacterium. Note that lactobacillus (top right) is indicated as surpressing bifidobacterium; this agrees with the above numbers.

This appears to illustrate that being focused on just one or two bacteria may not be the best path. A holistic approach (looking at what changes all of the bacteria above may be a critical step of improving things).

Antibiotic path

Long COVID is very similar to ME/CFS. Looking at antibiotics suggestions, about 60% of them are commonly use bt ME/CFS specialists. These areL

My personal preference would be one round of metronidazole, a three week break then minocycline, another break and then one of the other ones. This is following Dr. Jadin’s Current Protocol for ME/CFS using antibiotics

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.

Multiple Chemical Sensistivity With Mast Cell Issues

Back Story

I’m at the end if my rope and need help. I’m at my wits end with:

  • mcas and
  • mcs.

I was hit by levaquin in 1/14/20. It killed off my microbiome 22 days later reactions started. I believe has Sibo since then but was confirmed 4/23 and 4/24: Methane and hydrogen

I started raw milk one year ago and was able to stop food and scent reactions I was 85% better until March when dryer sheets on someone I m home set me off then a true anaphylactic event on 4/1 needing epi pen. Since raw milk I developed sulphur intolerance

I’m miserable and like ready for assisted suicide… but not seriously. I can’t deal with it anymore the ecoli albertii is way high 97% higher than everyone who took Biomesight so is methanobacter smithii I can’t tolerate any of the sulphur products since raw milk over grew stuff making me sulphur sensitive to microbes releasing sulphur. I never had issues with sulphur before raw milk one year ago!!!! I used to soak in Epsom all the time and eat garlic and broccoli like crazy that all stopped with this over growth!!!

My mast cell reactions and brain fog are once again bad. I do have mthfr do it’s hard to detox not sure that matters

Initial Analysis

As a start point, this has the lowest eubiosis that I have reviewed. Eubiosis is a computation on the chart below it. We see a lot of different species at abnormally high levels. A balance gut would have all of the blue lines close to the red lines.

There are a number of these bacteria that are strongly associated statistically with different symptoms.

I added the symptoms cited and went over to the new “Symptoms associations to Taxon, Compounds and Enzymes” to give this new feature an actual data case.

Comorbid: Multiple Chemical Sensitivity

Checking Enzymes for other conditions for possible vitamin impact.

Oral Bacteria Leakage

Looking at this new feature, we see three bacteria that stand out.

I did a hand-picked suggestions on just these three to see what can likely be done:

I went to another person that used the same lab that I know with both of these conditions and we see something in common

The LLM comment stated: Metabolic Interactions: Some Veillonellaceae bacteria, including Dialister species, are known for their metabolic interactions with other bacteria in the microbiota. They can metabolize certain compounds produced by other bacteria…

Going Forward

I am going to do “Just give me Suggestions include Symptoms” with the revised algorithm (see Algorithm for “Just Give Me Suggestions”) . I could have hand picked each bacteria associated with symptoms, but given the number of very high, this would likely produce similar effect with less effort.

This results in the Consensus having 7 sets of suggestions

Suggestions To Take

The top, non-prescription items are below. It is full of spices and herbs with just one vitamin and one probiotic.

Modifier
cinnamon (oil. spice)
oregano (origanum vulgare, oil)
vitamin b2,Riboflavin
thyme (thymol, thyme oil)
nigella sativa seed (black cumin)
garlic (allium sativum)
foeniculum vulgare,fennel
rosmarinus officinalis,rosemary
green tea
Hesperidin (polyphenol)
vegetable/fruit juice-based diets
naringenin(grapefruit) (Flavonoid)
neem
lactobacillus kefiri (NOT KEFIR)
peppermint (spice, oil)
syzygium aromaticum (clove)
triphala

Looking at probiotics, we have a good number that would allow easy rotation of probiotics. Two are usually difficult to obtain: lactobacillus kefiri and lactobacillus sakei . Most are available at my usual two preferred sources: Custom Probiotics and Indian Bulk Exporter (Maple Life Sources). See this list for sources not available there. By rotation, I mean 20-50 BCFU daily of one probiotic for 2 weeks and then change to another probiotic.

lactobacillus kefiri (NOT KEFIR)
lactobacillus casei (probiotics) [CB,MLS]
lactobacillus sakei (probiotics)
lactobacillus salivarius (probiotics) [CB,MLS]
lactobacillus reuteri (probiotics) [CB,MLS]
bifidobacterium infantis,(probiotics) [CB,MLS]
enterococcus faecium (probiotic)
lactobacillus paracasei (probiotics) [CB,MLS]
clostridium butyricum (probiotics),Miya,Miyarisan

Items to Reduce or Avoid

The top items are below. In relationship to the take, it seems clear that spices and herbs may be critical — increasing vegetables may have limited benefit. Spices and herbs can be done as capsules, teas, oils or just putting on food.

Modifiers To Avoid
resistant starch
Slippery Elm
ß-glucan
arabinogalactan (prebiotic)
chestnut tannins
Pork
rice bran
aspartame (sweetner)
quercetin,resveratrol
navy bean
vitamin B3,niacin
high fiber diet
partially hydrolyzed guar gum
Bofutsushosan
Pumpkin
moderate-protein moderate-carbohydrate
resistant maltodextrin

The question of milk came up. AVOID . If you need a milk like substance, use Soy milk only – other milks will contain milk sugar.

  • Cow milk 4mg per 100ml
  • Goat milk 0.6mg per 100ml
  • Soy milk 0mg per 100ml

Bottom Line

This is an interesting sample, the very high number of high percentile bacteria (with corresponding low Eubiosis) present some challenges. The interesting thing is that just targeting the high percentile ones produce a similar set of suggestions as the “Just Give Me Suggestions”. The item that is interesting is the massive number of different herbs at the top of the list. With the Oral Bacteria leakage issue, strive to take them as teas.Caffeine is a weak to be avoided, so it looks like herb teas (without caffeine — i.e. not black teas with herbs, just pure herbs) will be the regular beverage.

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.