A reader forwarded this 2019 study Dehydration affects exercise-induced asthma and anaphylaxis [Oct 2019]. Soem quotes:

 PubMed was searched from April to July of 2019 using predefined search terms “dehydration,” “exercise,” and “allergy responses.” Based on the reference search, more than one-hundred articles were identified
Also, numerous mast cells and eosinophils were recruited, therefore isotype switching to IgE antibodies occur, this hypersensitivity activates mast cell degranulation. After degranulation, proteases, leukotrienes, prostaglandins, and histamine lead to many kinds of allergy symptoms.

A few months ago, I wrote Hydration and the Microbiome which reviewed some literature.

The event that caused me to start looking at hydration, was a cheap home hydration device — a modern blue tooth scale, the one below. Currently $20.

As a result, because I was definitely dehydrated (but did not feel dehydrated — because that had been my new norm!) and proceeded to work on increasing hydration. At the start, I was 45.4% and have slowly worked it up to the current 47.2%. My goal is at least 57%, the middle of the normal range (ideally over 65%). My significant other has mast cell issues and was sitting well below 45% and is working on this change. One of the challenges is finding alternatives for items she takes that are known to cause dehydration — including antihistamines.

• Antihistamines, Blood pressure medicines, Chemotherapy, Diuretics, Laxatives. (U of Michigan)

So there is the appearance of a feedback loop: dehydration triggers mast cells, which result in the need for antihistamines, which then causes dehydration. The person is trapped!

A longer list from Oxford Medical:

• Fybogel, Lactulose, Macrogol, Senna, Bisacodyl, Docusate
• Antacids
• Ibuprofen, Naproxen, Diclofenac
• Loratadine, Cetirizine, Promethazine, Hydroxyzine
• Lisinopril, Ramipril, Losartan, Amlodipine, Felodipine, Bendroflumethiazide

In terms of the microbiome environment, we can see the impact from this study

Dehydration was accompanied by cell changes in solitary lymphoid nodules and Peyer’s patches. The proportion between lymphocytes, macrophages, and mast cells in lymphoid organs depended on the stage of dehydration. The inhibition of cell mitoses, disappearance of mature plasma cells and mast cells (per field of view), significant decrease in lymphocyte count, 4-5-fold increase in the number of destructive cells, and low density of cells and lymphatic network of the small intestine (per unit area) were observed on days 6 and 10 of dehydration. Severe morphological changes were also revealed in other layers of the small intestinal wall (mucosa, submucosa, lamina propria, etc.).

Effect of dehydration on morphogenesis of the lymphatic network and immune structures in the small intestine [2008]

Bottom Line

Hydration plays a very important role for health. Drinking 6 liters of water/day is the classic health advice. This may be a over simplification. This area is still being studied. “As the most effective sports nutrition supplement, sports beverage has different ingredients and formulas, and also has various effects. To provide clues for the development of sports beverage, this article reviews the types, components, effects, and mechanisms of sports beverage currently used in post-exercise fluid restoration.”[Research Progress on Application of Sports Beverage to Post-exercise Fluid Restoration, 2021] So some sports drink may help, some may have little effect.

An unexpected side effect, I did not change my diet habits but with the shift of hydration, I also lost 12 lbs (6 kilos) over 7 weeks.

Several pages has been added that should help people pick and understand probiotic impact better

Picking Probiotics for a Condition

Page: https://microbiomeprescription.com/Library/ProbioticSearch

This page will search over 3000 studies on the US National Library of Medicine for studies that:

• Used probiotic strains that are available as retail products
• Mentions the word you search for in the study

We then add the name of the product containing it, with a link to a site selling it. There may be other products that also include it.

Why I react to one probiotic but not the other

This does a cascade, from the probiotic mixture we look at all of the species/strains in it, then we go over to the KEGG: Kyoto Encyclopedia of Genes and Genomes and lookup the enzymes being produced by these bacteria. From these enzymes, we look up the products being produced.

When you compare two probiotics mixtures, you may not that one produces a lot more of some products than the other. These are likely candidates for why you have a different response.

page: https://microbiomeprescription.com/library/ProbioticCompoundCompare

Walk Thru

This is a special, off topic post resulting from some readers request. It is particularly important in the face of Omicron.

As always, I use gold standard sources:

Off-Label use of some Prescription Medicine

• Bacillus calmette-guerin [Tuberculosis] vaccination. [2021] decrease risk by 50%
• “Despite some controversies, numerous studies have reported a significant association between the use of ACE inhibitors and reduced risk of COVID-19″ [2021]
  • “The results obtained from this study showed that Ramipril, Delapril and Lisinopril could bind with ACE2 receptor and [SARS-CoV-2/ACE2] complex better” [2021] – these are often prescribed for high blood pressure and appear to drop the levels of ACE2 significantly within a week.

Supplements

There is a mountain of speculation and few actual trials (Traditional medicines prescribed for prevention of COVID–19: Use with caution.). Often the criteria to suggest something is the belief that the substance will improve the immune function. This is actually a two edge sword — a stronger immune response can make someone sicker. Herbal Immune Booster-Induced Liver Injury in the COVID-19 Pandemic – A Case Series [Dec 2021]. Other suggestions are based on treating symptoms like coagulation with serrapeptase — suggested but not tested. Others on their impact on  interleukins. virus titers, and interferon (IFN – for example from probiotics — again, suggested/speculated with no clinical trials.[See Probiotics Against Viruses; COVID-19 is a Paper Tiger: A Systematic Review [2021]

• “The findings from our study suggest that zinc supplementation in all three doses (10, 25, and 50 mg) may be an effective prophylaxis of symptomatic COVID-19 and may mitigate the severity of COVID-19 infection. “[2021]
• “This meta-analysis indicates a beneficial role of vitamin D supplementation on ICU admission, but not on mortality, of COVID-19 patients.” [2021]
  • ” There is no data from interventional trials clearly indicating that vitamin-D supplementation may prevent against COVID-19.” [Dec 2021]
• “Evidence supporting the therapeutic use of HDICV(high-dose intravenous vitamin C) in COVID-19 patients is lacking.” [2021]
• Withania somnifera [Ashwagandha] showed the highest binding affinity and best fit … may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication. [2021]
  • Withania somnifera as a safer option to hydroxychloroquine in the chemoprophylaxis of COVID-19: Results of interim analysis [2021]
  • “. Overall, the simulation run confirms the stability and rigidity of the interactions of Withanolide R and 2,3‐Dihydrowithaferin A from Withania somnifera to be the most potent phytochemical inhibitor for the main protease and the spike protein respectively. ” [2020]
  • More studies
• “The study found a reduced risk of COVID-19 infection in participants receiving neem(Azadirachta Indica A. Juss) capsules” [2021]
  • Screening of potential drug from Azadirachta Indica (Neem) extracts for SARS-CoV-2: An insight from molecular docking and MD-simulation studies[2021]

Items with In Vitro Evidence that it may help

Remember that In Vitro often fails to reproduce with humans.

• Pomegranate Peel Extract [2021]
• Quercetin [2021] [2021]

After Infection

In theory, some of these items may slow the infection by slowing the mechanisms of the infection.

• “Network Pharmacology Reveals That Resveratrol Can Alleviate COVID-19-Related Hyperinflammation” [2021[
• This search gives other interesting leads for substance that may help based on Network Pharmacology, many of them are herbs used in Chinese medicine. Some candidates are:
  • Glycyrrhizic Acid  (Licorice) [2021]
  • Quercetin [2021]
• Selenium [2021]

Bottom Line

If you find additional gold standard studies done on actual people, please forward them to me for inclusion on this page.

Person Description

• 32 year old male living in Scandinavia
• Health problems started at 16 years(possible overtrainig).
• Symptoms:
  • Every night my body collapses,
    • my nose gets extremely red (rosacea),
    • pulse rises and it feels strange in my body.
    • Delayed if does not eat dinner.
  • Feel very tired and can’t work out or even go short walks without getting tired (
    • mild CFS – diagnosed by a healthcare practitioner at 25 years
  • Brain fog.
  • Frozen/poor circulation in the body.
  • My body feels stressed,
  • Always feel and hear my pulse in the ears/head.
  • Problem with allergies/hypersensitivity to pollen, animals, strong fragrances, and against a lot of foods that I find difficult to identify.
  • Starting to get a lot of grey hair (none of my parents got grey hair in such a young age).
  • Diagnosed with SIBO 2 years ago.
  • Diagnosed with Epstein-Barr virus 4 years ago. 

I have done a lot of different protocols but it none really help. Most beneficial for the red nose (rosacea) is eating a diet is consuming low meat, low fat, low starch and eat a lot of fruits, juices and smoothies.

Comment: My own experience dealing with a ME/CFS relapse was that they first test-change-retest cycles had little/slow progress (See my progress reports). He reported some positive change from the first cycle,

Microbiome Tests

First microbiome test in late August, 2021. Upload to Microbiome Prescription resulted in the following protocol:

• Week 1-2: Rifaximin (as I understand you are not a fan of Rifaximin, but it was one of my top modifiers and I am also diagnosed with SIBO and have huge issues with rosacea on the nose). 
• Week 3-4: HMOWeek
• 5-6: Resveratrol, D-ribose (which I’m going to continue taking) and DAO.
• Week 7-8: Symbioflor 2.

From this changes, he reported a little more energy, but no real progress with my rosacea. Biomesight is processing his second test – will be ready in 1-3 weeks.

He is able to get antibiotics prescribed and He is also willing to take antibiotics.

Analysis

Rosacea

Rosacea is one of the conditions that I maintain in my US National Library of Medicine microbiome shifts list [rosacea]. The number of studies is few. In keeping with best practices (combining clinical studies with microbiome results) I checked Clinical Studies, I found Rosacea: Treatment targets based on new physiopathology data [Dec 7, 2021] lists “treatment targets and possible treatments:

1. permanent vascular changes (medical and instrumental treatments);
2. flushing (betablockers, botulinum toxin);
3. innate immunity (antibiotics, nonspecific antioxidants and anti-inflammatory molecules);
4. a neurovascular component (analgesics, antidepressants);
5. Demodex (antiparasitic drugs);
6. microbiome;
7. skin barrier impairment (cosmetics and certain systemic drugs);
8. sebaceous glands (isotretinoin, surgery);
9. environmental factors (alcohol, coffee, UV exposure). “

So, approaching it via the microbiome is in agreement with latest clinical practice. We should be aware that “Frozen/poor circulation” and “vascular changes” hints at a possible co-factor.

• “there is a lack of well-designed and controlled studies evaluating the causal relationship between rosacea and dietary factors.”  [2021]
• “Rosacea is triggered by hot and spicy food” [2021]

Reviewing literatures for Treatments and Clinical Studies

• Do not use metronidazole [2021]
• Possible doxycycline 40 mg/day – ongoing [2021] [2015] [2009]
• Minocycline 100 mg/day [2020]
• Gamma Linolenic Acid 320 mg/day [2020]
• “, mast cells (MCs) have emerged as key players in the pathogenesis of rosacea through the release of pro-inflammatory cytokines, chemokines, proteases, and antimicrobial peptides’ [2021] – hints at DAO and mast cell stabilizers
• silymarin/methylsulfonilmethane [2008]
• “Only 17% of those with rosacea were impaired by sunlight, whereas 26% improved. In the rosacea group, “[1989] – hints at Vitamin D
  • “Serum vitamin D was lower in patients with rosacea” [2018]
  • “The present study suggests that an increase in vitamin D levels may contribute to the development of rosacea. ApaI and TaqI polymorphisms, and heterozygous Cdx2, wildtype ApaI and mutant TaqI alleles were significantly associated with rosacea.” [2018]
  • SHORT FORM: Positive or negative response to sunlight/vitamin D depends on DNA

Looking at Suggestions from 1st Analysis

For a starting point, I used Advanced Suggestions. NOTE: The database is constantly being updated so suggestions on the same sample may change over time.

The results include some high weight items that was not included in his protocol. I checked if there was any results from clinical studies for Rosacea that used probiotics — I could not find any, thus the use of probiotics in a novel treatment approach. mutaflor escherichia coli nissle 1917 (probiotics) was included in take (so Symbioflor-2 is a valid substitution)

It is interesting that  Lactobacillus casei and L. paracasei degrades histamines [Post 2021] which should improve allergies/hypersensitivity reported.

Please note that some probiotics are on the to-avoid list, including:

• lactobacillus reuteri (probiotics)
• bifidobacterium infantis,(probiotics)
• bacillus coagulans (probiotics)
• clostridium butyricum (probiotics)
•  lactobacillus rhamnosus (probiotics)
•  bifidobacterium longum bb536 (probiotics)
•  enterococcus faecium (probiotic)

Dropping the Pub Med Filter for Rosacea, had some items that may impact circulation issues and mast cell issues positively:

•  resveratrol (grape seed/polyphenols/red wine)
•  quercetin,resveratrol

Further Digging

The suspected cause being overtraining lead me to the shifts know to occur. The literature is below

Citation
Intensive, prolonged exercise seemingly causes gut dysbiosis in female endurance runners. Journal of clinical biochemistry and nutrition (J Clin Biochem Nutr ) Vol: 68 Issue 3 Pages: 253-258 Pub: 2021 May Epub: 2020 Oct 31 Authors Morishima S , Aoi W , Kawamura A , Kawase T , Takagi T , Naito Y , Tsukahara T , Inoue R ,  Summary Html Article Publication
Rapid gut microbiome changes in a world-class ultramarathon runner. Physiological reports (Physiol Rep ) Vol: 7 Issue 24 Pages: e14313 Pub: 2019 Dec Epub: Authors Grosicki GJ , Durk RP , Bagley JR ,  Summary Html Article Publication
Physiological and Biochemical Effects of Intrinsically High and Low Exercise Capacities Through Multiomics Approaches. Frontiers in physiology (Front Physiol ) Vol: 10 Issue Pages: 1201 Pub: 2019 Epub: 2019 Sep 18 Authors Tung YT , Hsu YJ , Liao CC , Ho ST , Huang CC , Huang WC ,  Summary Html Article Publication
Improvement of non-invasive markers of NAFLD from an individualised, web-based exercise program. Alimentary pharmacology & therapeutics (Aliment Pharmacol Ther ) Vol: 50 Issue 8 Pages: 930-939 Pub: 2019 Oct Epub: 2019 Jul 25 Authors Huber Y , Pfirrmann D , Gebhardt I , Labenz C , Gehrke N , Straub BK , Ruckes C , Bantel H , Belda E , Clément K , Leeming DJ , Karsdal MA , Galle PR , Simon P , Schattenberg JM , Summary Publication Publication
Home-based exercise training influences gut bacterial levels in multiple sclerosis. Complementary therapies in clinical practice (Complement Ther Clin Pract ) Vol: 45 Issue Pages: 101463 Pub: 2021 Jul 30 Epub: 2021 Jul 30 Authors Mokhtarzade M , Molanouri Shamsi M , Abolhasani M , Bakhshi B , Sahraian MA , Quinn LS , Negaresh R ,  Summary Publication
Are nutrition and physical activity associated with gut microbiota? A pilot study on a sample of healthy young adults. Annali di igiene : medicina preventiva e di comunita (Ann Ig ) Vol: 32 Issue 5 Pages: 521-527 Pub: 2020 Sep-Oct Epub: Authors Valeriani F , Gallè F , Cattaruzza MS , Antinozzi M , Gianfranceschi G , Postiglione N , Romano Spica V , Liguori G ,  Summary Publication
Effect of an 8-week Exercise Training on Gut Microbiota in Physically Inactive Older Women. International journal of sports medicine (Int J Sports Med ) Vol: Issue Pages: Pub: 2020 Dec 15 Epub: 2020 Dec 15 Authors Zhong F , Wen X , Yang M , Lai HY , Momma H , Cheng L , Sun X , Nagatomi R , Huang C ,  Summary Publication Publication
The influence of exercise training volume alterations on the gut microbiome in highly-trained middle-distance runners. European journal of sport science (Eur J Sport Sci ) Vol: Issue Pages: 1-0 Pub: 2021 May 26 Epub: 2021 May 26 Authors Craven J , Cox AJ , Bellinger P , Desbrow B , Irwin C , Buchan J , McCartney D , Sabapathy S ,  Summary Publication

Although it was a long time ago for the over-exercising, I decided to see if some of the changes may have the appearance of long term persistence. Running the known shifts against the two samples, I was actually surprised to see the earlier test had far more matches to the literature than the last test. Some items dropped off and only one item was added. Given that he had been implementing suggestions between the two samples, the improvement is nice to see.

tax_name	tax_rank	Early Test Percentile	Last Test Percentile
Acidobacteria	phylum	2.18
Actinobacteria	phylum	7.85	3.91
Akkermansia	genus	0.71
Akkermansia muciniphila	species	0.85
Burkholderiales	order	26.90
Chroococcales	order	3.24	26.00
Clostridiaceae	family	97.81	98.68
Deferribacterales	order		86.6
Eubacteriales Family XIII. Incertae Sedis	family	14.75	6.56
Hyphomicrobiales	order	2.53
Moorella group	no rank	2.54
Prevotella bivia	species	75.47
Proteobacteria	phylum	13.97	14.64
Ruminococcaceae	family	21.02	8.95
Streptococcus australis	species	87.87	83.60
Streptococcus thermophilus	species	83.16
Streptococcus vestibularis	species	75.94
Sutterellaceae	family	18.94

Continuing this logical exercise, “What would be suggested if I keep my scope to counteracting only the shifts that may be ascribed to over-exercising?” This assumes that the over-exercised shift created a stable dysfunctional microbiome that persisted. To do this, I used my Biome View and hand picked the above items. Many of the items are also on the list above.

With one probiotic being well suggested (but likely difficult to get except by mail order). I included prescription items in the choices — none made it on the to add list, many appear on the to avoid list.

In terms of Flavonoids, Apples (I recall that at least 2 a day were needed from a study that I read recently) and Almonds (perhaps marzipan could work similarly… no studies, but given where he is, marzipan is definitely available)

Evaluating things tried

I recently added the ability to compare two samples in the light of taking some microbiome modifier (see this post for more details)

• Week 1-2: Rifaximin (as I understand you are not a fan of Rifaximin, but it was one of my top modifiers and I am also diagnosed with SIBO and have huge issues with rosacea on the nose).  Results: AGREES 25, DIFFERS:23
• Week 3-4: HMO Week AGREES: 62 DIFFERS:58
• 5-6:
  • Resveratrol, AGREES: 45 DIFFERS:40
  • D-ribose (which I’m going to continue taking) AGREES: 6.2 DIFFERS:2.4
  • DAO (Nothing in database)
• Week 7-8: Symbioflor 2. AGREES 0.5 DIFFERS:4.6
  • I decided to checked Mutaflor (it’s siblings) AGREES 4.1 DIFFERS 2.4

The goal of this website has always been “Better suggestions than random suggestions”. In our review above, we found that AGREES > DIFFERS except for Symbioflor-2. The shifts seen more typical for Mutaflor (E.Coli Nissle 1917 probiotic). What I found most interesting was that the modifier that the reader has decided to continue, d-ribose, was also the one with the best ratio between Agrees/Differ. D-ribose has been documented to improve ME/CFS and FM (see this post for study links)

I was pleased to see almost every modifier had positive impact, but wish the amount was more.

Other Threads?

There is a tendency to try to fix everything at one time. My preference is to focus always on one to two items between tests. We have two threads — Rosacea and Over-exercising. Suggestions are similar and I would say run with it for 2-3 months and then retest.

As illustrated here (and in this prior review), we have some objectivity in evaluating the effectiveness of microbiome modifiers between samples — it should be helpful in improved picks over a series of samples.

• If we review genus as an ethnic groups, we find over 3,365+ groups – each distinctive
  • Species are the equivalent of small business, community groups – we have 10,567+
  • Strains could be viewed as the individuals.
  • Some strains (people) are criminals and some community leaders
• To understand what is happening in the cities, we need to get data / characteristics
  • What foods are sent to the city
  • What products are exported from the city
  • What are the sources of energy for the city
  • How may people come in or leave by ethnic groups
  • What type of waste is produced by the city
  • What types of crimes happen in the city

From this information, we may gain insight into how to administer and change the city.

All of the above, except for End Products(Obsolete). This information is obtained from lab studies cultivating bacteria. Data is really hit and miss.

All of the other statistics is done using gene data from KEGG: Kyoto Encyclopedia of Genes and Genomes. Once the bacteria has been sequenced, all of this information can be computed. This works for both bacteria that can be cultured and those (most) that cannot be cultured in a lab.

Where do you find this data on Microbiome Prescription?

Seeing changes between Samples

When you have multiple samples, this line will appear. Multiple Samples Comparison is the button

These reports are the same as above – except you have numbers from different samples side by side

What is the difference between Outliers and Full Report?

Outliers ( AKA out of range) gives you the ability to filter by percentile OR use the Kaltoft-Moldrup Limits

The full range gives a much larger list (often hundreds) with filtering limited to the Search box on the page.

Above is for an individual sample — so you are given a list of your samples and the page will automatically update when you change samples.

For the multiple sample compare, you have already selected the samples and cannot change them from the page. You can go back to the selection page and pick different samples.

For multiple sample outliers — if one sample has an outlier, then the values of other samples will also be shown. The outliers are color coded:

VIDEOS COMING

The reader provide the following history (shortened)

Person’s Narrative

Sample BiomeSight:2021-02-24 In addition to my usual CFS symptoms I had a lot of trouble with gastritis. I was taking Slippery Elm, Marshmallow root, DGL, melatonin, magnesium, probiotic Bio.me Femme UT. I mostly avoided other supplements due to gastric issues. When the results came back I was only able to eat a few foods, so I couldn’t really follow the suggestions. I decided to wait until my stomach got better and retest.

Sample BiomeSight:2021-08-23 Taken after I’ve been on PPIs for 3 months. I haven’t been eating dairy for months which decreased B. Wadsworthia somewhat. I ate a lot of soy milk and soy yogurt. Mostly gluten-free, but eating lots of oatmeal. The combination of PPIs and yogurt made Streptococcus Thermophilus very high. The supplements at the time were melatonin, magnesium, zinc carnosine, d3 & k2, vit A, Omega 3, probiotic Bio.me Femme UT, occasional Slippery Elm to calm the stomach.

After I got results back I started taking:
– Miyarisan (Kegg AI Computed Probiotics),
– glycine (Kegg AI Computed Supplements),
– inulin, burdock root, L. Rhamnosus, L.Reuterii, almonds, oregano tea (suggestions from Targeted bacteria based on symptom Impaired memory & concentration).
I alternated modifiers so I wasn’t taking all of them all of the time.

I stopped:
– vit A and Slippery Elm (suggestions from Targeted bacteria based on symptom Impaired memory & concentration)
– yogurt (high S. Thermophilus)- oatmeal (it seemed to cause hypoglycemia. Replaced with tsampa – roasted barley flour)

Interestingly, Kegg AI Computed Supplements at level <15% reported Iron and 6 weeks later I was found to be anemic. That was an excellent prediction! I wish I would have gone and tested my iron status right away.

Sample BiomeSight:2021-11-28 Still on PPIs. Taken one month after I started taking prescription iron pills and lactulose to help with resulting constipation. Still eating soy milk daily, but no dairy, no yogurt. Taking more supplements at this point.

Analysis

Reading the history, my first question is to see if the predicted shifts from doing PPI (Proton Pump Inhibitors) is reflected between samples. Keep in mind that there are other microbiome compounders (i.e. other eating pattern changes). To this end, I’ve created a new page where you can pick a before, after and a modifier.

What is interesting to note is that the impact diminished overtime (80 -> 65). This agrees with my base model that rotation and re-testing is essential.

We can do combinations, for example PPI and melatonin between first and second sample. We lack studies on combinations and thus have to resort to this experiential approach to see how well predictions agree with actuals.

At the bottom of the pages, you get the details:

If a substance did not cause more improvements(Agrees versus Differs), then they are possible items to drop. Remember, the suggestions are theoretical prediction looking at many hundreds of bacteria. This allows you to objectively measure whether they worked well for you! They will not work for every one because of differences in DNA, diet, gender, age etc. I spot checked items like Slippery Elm (46.8 Agrees, 27 Differs), Miyarisan (KEGG Suggestion) (40.8 Agrees, 15 Differs) and was pleased with the results.

Looking at the next Step

Above, we (to my delight) verify that the suggestions are causing changes in the predicted direction for this person (based on their microbiome samples). Looking at predicting symptoms, we had 72% correct for the top 11 items ( So where do we go from here? Remember, the goal is to focus on the bacteria that likely contributed the most to the dysfunction (often high ones)

• From KEGG, the best probiotic is Sun Wave Pharma/Bio Sun Instant, if it is available. It has several species suggested in it.
• Looking at KEGG Products out of range — 7 were too low and 190 were too high. We are looking at an overproduction scenario.

I looked thru the predicted symptoms bacteria and there were a lot of secondary matches(shown with a # but very few direct matches. When we moved on to KM outliers, we had 25 items listed — 2 families and 5 genus with these items of considerable note — both for high percentile and high numbers:

• (family) Oscillospiraceae – 99.8%ile -18%
• (genus) Streptococcus – 98%ile – 4.2%
• (genus) Phocaeicola – 99%ile – 3.6%

So I did a hand picked with just these more extreme values. I tossed in everything we had. No prescription items showed up on the to take, but many (and a few b-vitamins) showed up on the to avoid list.

In terms of typical ME/CFS, we found only two matches, both two high:  Bacteroides ovatus and Streptococcus. In terms of this small subset — only one item was above 0.29 — Human milk oligosaccharides (prebiotic, Holigos, Stachyose) with iron and B-12 being on the to take list.

We also note that the Unhealth Bacteria page, was full of Streptococcus

I tossed all of these into our hand-picked list and ask for new suggestions — the suggestions did not change expect for minor shifts of confidence.

Bottom Line

Two probiotics:  lactobacillus plantarum (probiotics) and the mixture Sun Wave Pharma/Bio Sun Instant. I see the recommendation leads to the same type of breakfast that is regular for me: Barley/Oats with inulin and wheat bran. For all of the items, make sure you check the dosage links (where available)

The Microbiome is like a city full for billions of bacteria (people).

• Some items produced in the city are consumed in the city – for example, Bakery products
• Some items are imported into the city – for example, Wheat to make bread
• Some items are exported from the city – for example, factory goods

Similarly there are compounds / chemicals in the microbiome. Some imports may be coming from food or cells in the body, products out to be going to cells or into urine, some products are consumed by other bacteria

The intent of this new page is to attempt to get estimates of these flows. These are crude estimates because they depend on two things — the bacteria species identified by the lab (different labs detect different species) and whether the full genes of each species is in KEGG.

The flow is simple as illustrated below

1. The Stool sample is sent to a lab
2. The lab process it and produces a data file (“Fastq”)
3. The lab runs it thru software that produces a list of bacteria and their count
4. We then take all of the species reported that are found in KEGG and compute the count of enzymes. We assume one bacteria produces one enzyme.
5. From the totals of each enzymes, we go back to KEGG to find what is consumed (Substrate) by the enzyme, and what is produced by the enzymes. Again, we assume 1 unit of compound is produced for 1 unit of enzyme.
6. We total all of the compound being produced and consumed.
7. We then get the distribution over all samples and compute a percentile value for each.

Needless to say, that is a lot of calculations — a lot!

The New Page

The page is under Component Analysis as shown below

When the page for a sample loads, you may be missing the percentiles. This is done because of the amount of calculation involved, it is not done automatically.

At the top of the page is a button, just click it and wait a little while and the percentiles will appear

Use the search button to find items that you are interested in, For example, in how much of D-Lactic and L-Lactic acid is being produced and consumed. High D-Lactic acid is associated with brain fog. Remember that comparison must be done with the same lab software identifying.

Bottom Line

This is likely a useful tool for tracking changes between samples. Go to it and add comments when you find interesting things.

This is similar to Kombucha, see my prior post from 2017 here. Every species (and strains) have different impacts and I prefer to reduce the risk of adverse outcomes.

“Similarly to milk-derived kefir, the exact microbial composition of kombucha cannot be given because it varies. “

 A Review on Kombucha Tea—Microbiology, Composition, Fermentation, Beneficial Effects, Toxicity, and Tea Fungus [2014]

Great good can come from Kefir, for example, the probiotic Lactobacillus Kefiri LKF01 (DSM 32079) LKEF. It was discovered after investigating dozens of different Kefirs. See this 2017 post on this probiotic.

Kefir can contain many different species and families — including [2008] [2021] [2015] [2011] [2006]

• Lactobacillus kefiri (occasionally)
• Lactobacillus  kefiranofaciens
• Leuconostoc mesenteroides 
• Lactococcus lactis 
• Liquorilactobacillus nagelii,
• Lentilactobacillus hilgardii/diolivorans
• Lacticaseibacillus casei/paracasei,
• Lactobacillus perolens,
• Lactobacillus parafarraginis,
• Lactobacillus diolivorans,
• Oenococcus oeni 
• Lactobacillus acidophilus,
• Streptococcus thermophilus, 
• Sphingobacterium

The grains used, the processes and environment, all contribute to variable outcomes.

Bottom Line

I have a strong bias in wanting to know precisely what bacteria are being taken. “Fermented drinks are good” is gospel for many…. for me, it is randomness… some people will do good and some will not – often dependent on the brand, or how it was fermented….. I am risk adverse…

Kefir grains could come salted with specific bacteria (to increase the odds) — but I would expect that the provider would provide information on the strains and links to the literature for each.

Comments

This list (with live time updates as data is added) on Microbiome Prescription web site. All suggestions from this page should be reviewed by your medical professionals. These are based on modelling and not clinical studies. These are based on family and lower taxonomy ranks (genus,species,strains) reported in studies on US National Library of Medicine.

In general, people report improvements from at least half of the items on the top of the list for other conditions. Many items listed have been reports in clinical studies to help a significant percentage of patients.

Items with a low bad impact and high good impact are likely the best to start with (i.e. Sumac(Rhus coriaria) , laminaria hyperborea( tangle/cuvie – seaweed)  thyme  (oil), coriander oil  , peppermint  oil). Many of these suggestions are similar to those for Chronic Fatigue Syndrome (Long COVID sibling). Suggestions for ME/CFS agreed with clinical studies results.

Reversion of Gut Microbiota during the Recovery Phase in Patients with Asymptomatic or Mild COVID-19: Longitudinal Study. Microorganisms (Microorganisms ) Vol: 9 Issue 6 Pages: Pub: 2021 Jun 7 Epub: 2021 Jun 7 Authors Kim HN , Joo EJ , Lee CW , Ahn KS , Kim HL , Park DI , Park SK , if(open==true){ } Summary Html Article Publication

The gut microbiome of COVID-19 recovered patients returns to uninfected status in a minority-dominated United States cohort. Gut microbes (Gut Microbes ) Vol: 13 Issue 1 Pages: 1-15 Pub: 2021 Jan-Dec Epub: Authors Newsome RC , Gauthier J , Hernandez MC , Abraham GE , Robinson TO , Williams HB , Sloan M , Owings A , Laird H , Christian T , Pride Y , Wilson KJ , Hasan M , Parker A , Senitko M , Glover SC , Gharaibeh RZ , Jobin C , if(open==true){ } Summary Html Article Publication

Gut Microbiota May Not Be Fully Restored in Recovered COVID-19 Patients After 3-Month Recovery. Frontiers in nutrition (Front Nutr ) Vol: 8 Issue Pages: 638825 Pub: 2021 Epub: 2021 May 13 Authors Tian Y , Sun KY , Meng TQ , Ye Z , Guo SM , Li ZM , Xiong CL , Yin Y , Li HG , Zhou LQ , if(open==true){ } Summary Html Article Publication

Gut Microbiota Interplay With COVID-19 Reveals Links to Host Lipid Metabolism Among Middle Eastern Populations. Frontiers in microbiology (Front Microbiol ) Vol: 12 Issue Pages: 761067 Pub: 2021 Epub: 2021 Nov 5 Authors Al Bataineh MT , Henschel A , Mousa M , Daou M , Waasia F , Kannout H , Khalili M , Kayasseh MA , Alkhajeh A , Uddin M , Alkaabi N , Tay GK , Feng SF , Yousef AF , Alsafar HS , if(open==true){ } Summary Publication

Best prediction is done when using a 16s microbiome result for the patient

Net	Modifier2	Good Impact	Bad Impact
24	bacillus subtilis (probiotics)	34	10
21	lactobacillus casei (probiotics)	30	9
20	pomegranate	27	7
19	resistant starch	34	15
19	whey	22	3
19	bifidobacterium longum (probiotics)	22	3
18	pediococcus acidilactic (probiotic)	21	3
17	brown rice	23	6
17	wheat	24	7
17	oregano (origanum vulgare, oil) |	24	7
16	almonds/ almond skins	18	2
15	soy	25	10
15	vitamin d	29	14
14	walnuts	27	13
14	whole-grain barley	22	8
14	pectin	22	8
14	wheat bran	24	10
14	Cacao	21	7
14	dietary fiber	14	0
14	lactobacillus plantarum,xylooligosaccharides,(prebiotic) (probiotics)	16	2
14	lactobacillus reuteri (probiotics)	27	13
14	fish oil	17	3
14	proline (amino acid)	19	5
14	bifidobacterium bifidum (probiotics)	25	11
13	lactobacillus paracasei (probiotics)	22	9
13	lactobacillus acidophilus (probiotics)	22	9
13	Human milk oligosaccharides (prebiotic, Holigos, Stachyose)	28	15
12	raffinose(sugar beet)	16	4
12	lauric acid(fatty acid in coconut oil,in palm kernel oil,)	17	5
12	high fiber diet	20	8
12	rosmarinus officinalis (rosemary)	25	13
12	Conjugated Linoleic Acid	14	2
12	Alpha-Ketoglutarate	18	6
12	Burdock Root	16	4
11	glycine	17	6
11	Glucomannan	11	0
11	pea (fiber, protein)	16	5
11	fructo-oligosaccharides (prebiotic)	26	15
11	lactobacillus rhamnosus (probiotics)	23	12
11	lactobacillus rhamnosus gg (probiotics)	19	8
11	lactobacillus casei shirota (probiotics)	13	2
11	fat	20	9
11	bifidobacterium pseudocatenulatum,(probiotics)	15	4
11	bifidobacterium infantis,(probiotics)	17	6
11	polyphenols	14	3
11	saccharomyces boulardii (probiotics)	20	9
11	oligofructose (prebiotic)	12	1
11	apple	21	10
11	whole grain,bran	11	0
10	vsl#3 (probiotics)	14	4
10	naringenin(grapefruit) (Flavonoid)	13	3
10	lupin seeds (anaphylaxis risk, toxic if not prepared properly)	20	10
10	magnesium	12	2
10	red wine	23	13
10	broad beans	20	10
10	fasting	16	6
10	lactobacillus plantarum (probiotics)	28	18
10	inulin (prebiotic)	26	16
10	enterococcus faecium (probiotic)	15	5
10	hou-po-da-huang-tang	11	1
9	Goji (berry,juice)	15	6
9	fruit/legume fibre	16	7
9	oligosaccharides (prebiotic)	12	3
9	banana	10	1
9	bifidobacterium adolescentis,(probiotics)	12	3
9	bifidobacterium animalis lactis (probiotics)	16	7
9	anise	13	4
9	triphala	34	25
9	zinc	27	18
9	vitamin a	23	14
8	trametes versicolor( mushroom)	10	2
8	red chiles (Capsicum)	8	0
8	xylooligosaccharide (prebiotic)	9	1
8	thyme	15	7
8	trametes versicolor(Turkey tail mushroom)	10	2
8	peppermint	13	5
8	persimmon tannin	9	1
8	resistant maltodextrin	16	8
8	selenium	9	1
8	mediterranean diet	21	13
8	omega-3 fatty acids	14	6
8	palm kernel meal	12	4
8	bifidobacterium catenulatum,(probiotics)	10	2
8	bacillus subtilis natto (probiotics)	9	1
8	cinnamon (oil. spice)	21	13
8	high resistant starch	12	4
8	green tea	14	6
8	jerusalem artichoke (prebiotic)	11	3
8	ketogenic diet	18	10
8	noni	12	4
8	Acacia Gum	9	1
8	bacillus,lactobacillus,streptococcus,saccharomyces probiotic	8	0
8	yogurt	8	0
8	sarcodiotheca gaudichaudii (red sea weed)	11	3
8	brown algae	11	3
8	Soymilk	8	0
7	plantago asiatica l.	12	5
7	lactose	11	4
7	Codonopsis pilosula	7	0
7	rosa rugosa	11	4
7	dietary phytoestrogens (isoflavones)	12	5
7	chicken	7	0
7	sialyllactose (oligosaccharide ) (prebiotic)	11	4
7	polygonatum kingianum(Orange Flower Solomon’s Seal.)	7	0
7	arabinoxylan oligosaccharides (prebiotic)	20	13
7	bacillus pumilus	9	2
7	lactobacillus gasseri (probiotics)	16	9
7	glutamate	7	0
7	foeniculum vulgare (Fennel)	12	5
7	dates	9	2
7	black raspberries	12	5
7	arabinogalactan (prebiotic)	8	1
7	garlic (allium sativum)	20	13
7	neem	13	6
7	methyl gallate	10	3
7	polysorbate 80	11	4
7	Vitamin B-12 (Cyanocobalamin)	7	0
7	blueberry	12	5
6	buckwheat	8	2
6	vitamin b2(Riboflavin)	7	1
6	germinated barley food-stuff	6	0
6	schinus molle (herb)	7	1
6	raw potato starch	10	4
6	sesame cake/meal	7	1
6	safflower oil	7	1
6	barley	25	19
6	chicory (prebiotic)	8	2
6	chrysanthemum morifolium	12	6
6	fibre-rich macrobiotic ma-pi 2 diet	13	7
6	daesiho-tang	6	0
6	lactobacillus salivarius (probiotics)	16	10
6	lactobacillus brevis (probiotics)	9	3
6	Lactobacillus Johnsonii (probiotic)	12	6
6	Oyster Mushroom	7	1
6	corn	6	0
6	sesame	7	1
6	rye	7	1
6	grape fiber	6	0
6	chondrus crispus (red sea weed)	9	3
5	xylaria hypoxylon (fungi)	7	2
5	lactobacillus sakei (probiotics)	5	0
5	purple sweet potatoes	9	4
5	d-ribose	5	0
5	Whole Milk	6	1
5	brassica juncea	9	4
5	galla rhois	8	3
5	Kiwifruit	7	2
5	lactobacillus acidophilus,cellobiose (probiotics)	6	1
5	gum arabic (prebiotic)	6	1
5	chamomile (chamaemelum nobile)	8	3
5	cabbage	5	0
5	barley,oat	15	10
5	basil	6	1
5	bacillus (probiotics)	5	0
5	rhubarb	14	9
5	navy bean	15	10
5	n-acetyl-d-glucosamine	5	0
5	oats	7	2
5	bifidobacterium lactis bb12 (probiotics)	10	5
5	green-lipped mussel	11	6
5	genistein	8	3
5	salt (sodium chloride)	8	3
4	saccharomyces cerevisiae (probiotics)	9	5
4	sesuvium portulacastrum herb	5	1
4	tulsi	5	1
4	vegetable	4	0
4	resveratrol (grape seed/polyphenols/red wine)	24	20
4	tannic acid	10	6
4	marijuana	6	2
4	pea protein	7	3
4	mutaflor escherichia coli nissle 1917 (probiotics)	5	1
4	moderate-protein moderate-carbohydrate	5	1
4	marjoram	5	1
4	rosa canina	4	0
4	plantain bananas	4	0
4	bifidobacterium longum bb536 (probiotics)	13	9
4	black beans	7	3
4	chitosan,(sugar)	20	16
4	glucose (sugar)	4	0
4	fruit	7	3
4	koji aspergillus oryzae	5	1
4	laminaria digitata(oarweed – seaweed)	9	5
4	Psyllium (Plantago Ovata Husk)	13	9
4	Beet	4	0
4	Bifidobacterium animalis	4	0
4	wasabi	4	0
4	fucoidan	5	1
4	punicic acid	4	0
4	asparagus	4	0
4	Vitamin E	4	0
4	Vitamin B	4	0
4	lemon	6	2
4	western diet	4	0
4	allium cepa	4	0
4	Opium poppy (Papaver somniferum)	4	0
4	Spearmint(mentha spicata)	4	0
4	Mango ginger(curcuma amada)	4	0
4	cinnamomum zeylanicum	4	0
4	cinnamomum tamala	4	0
4	Exercise	10	6
4	potatoes	10	6
4	bifidobacterium breve (probiotic)	6	2
4	spirulina(cyanobacteria)	4	0
4	low protein diet	12	8
4	papaya	4	0
4	bean	5	1
4	fenugreek	7	3
4	quercetin,resveratrol	13	9
4	rosehip tea	5	1
4	pomegranate blossom tea	5	1
4	grape polyphenols	13	9
4	hypericum scabrum herb	5	1
4	high amylose cornstarch	4	0
4	maize	4	0
4	mannitol	4	0
4	tabebuia impetiginosa (taheebo) bark	5	1
4	vitex negundo (herb)	4	0
3	nigella sativa seed (black cumin)	5	2
3	whole-grain wheat	5	2
3	sorghum	8	5
3	lactulose	14	11
3	bifidobacterium longum,lactobacillus helveticus (probiotics)	5	2
3	Curcumin	5	2
3	White-leaved Savory(micromeria fruticosa)	5	2
3	amaranth	8	5
3	Agavins (agave sugar)	7	4
3	avocado peel	4	1
3	Slippery Elm	30	27
3	Gallic acid	4	1
3	Ajwain (trachyspermum ammi)	6	3
3	Taxifolin	5	2
3	Ginseng	7	4
3	Lithium	9	6
3	Dendrobium officinale	7	4
3	lactobacillus fermentum (probiotics)	10	7
3	low animal protein diet	4	1
3	l-sorbose	4	1
3	fraxinus angustifolia (narrow-leafed ash)	3	0
3	capsaicin (hot pepper)	4	1
3	coriander oil	7	4
3	enterococcus durans (probiotics)	4	1
3	aspartame (sweetner)	9	6
3	animal-based diet	14	11
3	polymannuronic acid	17	14
3	momordia charantia(bitter melon, karela, balsam pear, or bitter gourd)	5	2
3	low processed foods diet	4	1
3	lychee fruit (nephelium longan)	3	0
3	xylan (prebiotic)	13	10
3	xylitol	7	4
3	sunflower oil	4	1
3	syzygium aromaticum (clove)	7	4
3	galacto-oligosaccharides (prebiotic)	19	16
2	oolong tea polyphenols	3	1
2	oolong teas	3	1
2	tomato powder	3	1
2	tea	18	16
2	vitamim e	2	0
2	oligofructose-enriched inulin (prebiotic)	11	9
2	oregano essential oil	3	1
2	paenibacillus polymyxa (prescript assist) (probiotics)	3	1
2	olea europaea (olive leaf)	5	3
2	mint	2	0
2	satureia montana(Winter savory)	3	1
2	(+)-catechin	4	2
2	abies alba mill. (silver fir)	3	1
2	bioflorin,enterococcus faecium sf 68,(probiotics)	3	1
2	bacopa monnieri	2	0
2	carum carvi (Caraway)	3	1
2	catechol	3	1
2	choline deficiency	2	0
2	chitooligosaccharides (prebiotic)	14	12
2	chaga (mushroom)	2	0
2	grapes	4	2
2	l-phenylalanine	2	0
2	l-arginine	2	0
2	lemon oil	2	0
2	lemongrass oil	5	3
2	lactobacillus helveticus,lactobacillus rhamnosus (probiotics)	2	0
2	Pork	8	6
2	camellia	2	0
2	rice bran	6	4
2	Tryptophan	6	4
2	nobiletin	2	0
2	Konjaku flour	6	4
2	lactobacillus helveticus	2	0
2	bacillus laterosporus (probiotic)	6	4
2	Immortelle(helichrysum italicum)	3	1
2	milk thistle(silybum marianum)	2	0
2	bandicoot berry(leea indica)	2	0
2	Bacillus clausii (Probiotics)	4	2
2	bifidobacterium (probiotics)	6	4
2	xylopia aethiopica (herb)	2	0
2	cylicodiscus gabunensis (mimosaceae)	2	0
2	d-fructose (sugar)	2	0
2	lactobacillus paracasei,lactobacillus acidophilus,bifidobacterium animalis (probiotics)	3	1
1	galactose (milk sugar)	12	11
1	hydrogenated palm oil	1	0
1	bifidobacterium lactis,streptococcus thermophilus probiotic	8	7
1	galla chinensis (herb)	10	9
1	Sijunzi decoction	4	3
1	Baking Soda (Sodium Bicarbonate)	7	6
1	strawberry	4	3
1	Fiber, total dietary	3	2
1	Haritaki	1	0
1	quinoa	2	1
1	Cacoa flavonoids	1	0
1	lactobacillus kefiri (NOT KEFIR)	11	10
1	grape seed extract	8	7
1	fumarate	1	0
1	ginger	10	9
1	doenjang (fermented bean paste)	2	1
1	aloe vera	2	1
1	ashwagandha (withania somnifera)	3	2
1	bacillus licheniformis,(probiotics)	10	9
1	ß-glucan	17	16
1	salvia officinalis (sage)	1	0
1	plant-rich diet	1	0
1	peppermint (spice, oil)	5	4
1	moderate-carbohydrate diet	1	0
1	magnolia bark	2	1
1	peganum harmala (rue)	2	1
1	thyme oil	1	0
1	thyme (thymol, thyme oil)	8	7

The site also provide prescription suggestions with those below being the highest ranked.

This is a part of an ongoing series of posts that are intended for microbiome testing labs, or those interested in starting one. I am downstream from all of the microbiome labs and will gladly work with any of them — my main concern is making people better — not the financial bottom line.

This post looks at issues involved with selecting studies to use for giving suggestions to consumers of microbiome result. These are questions that I have looked at and have made my own choices (a.k.a. technically trade secrets).

Method of microbiome detection used

There are three main types, listed below. Do you restrict to only one? Do you give a weight to different methods, for example the values suggested after each below?

• Cultured Sample – Weight 0.1
• 16s Sample – Weight 0.8
• Metagenomics – Weight 1.0

For a discussion of the last two, see Comparison between 16S rRNA and shotgun sequencing data for the taxonomic characterization of the gut microbiota [2021]

Life Form/non-form that the study was done on

We have a wide variety of “bacteria incubators” reported in studies, including

• Fish (Zebra fish especially)
• Animals – which ones? Horses, Dogs, Cats, Cows, Pigs etc
• Chemical Reactors simulating some living creature’s environment
• Humans
  • Which ethnic groups
  • Location that the study was done (a proxy for diet) — different results from Mexico and Japan!
  • Age — children, adults and the elderly have different responses
  • Medical conditions in the cohort

Do you do a binary include/exclude or do you apply a weight to each?

Quality of Study

The following are commonly used in evaluating studies:

• Read Beyond the Abstract – that means getting and reading the full study, including the appendix
• Determine Whether All Results Were Included
• Observational Study versus Randomized Controlled Trial
• Odds Ratios and Confidence Intervals
• Size of study

Do you give different weights based on the above? Some literature is below:

• Understanding and evaluating clinical trials
• A General Framework for the Evaluation of Clinical Trial Quality
• A Simple Method for Evaluating the Clinical Literature

Interpreting Studies

Different studies report things differently. For example some may report the % change of a bacteria average, others may provide the actual distribution, others may just report that the control or the cohort average was higher with (P < 0.5). It is like trying to buy gas – one person is offering it by the gallon in US$, another in litres in Euro, a third “sufficient fuel to drive 200 miles in a 1958 Land Rover” for 3 oz of silver.

Method of Aggregation

Some studies use the Hartung–Knapp–Sidik–Jonkman random effects model [2021] to combine results. Other studies use DerSimonian-Laird method (cited by Cochrane) or The generic inverse variance outcome type in RevMan.

Bottom Line

I have my own magic in combining a multitude of studies and resolving the many many issues cited above. I encourage labs to do their own resolutions and then let people compare results (if they are in agreement, everyone should be happy). The real test is whether the suggestions work. So far, for my own experience and for a reasonable number of people that have provided feedback – they have. The suggestions may not be perfect, but my goal is to give suggestions that are more likely to help.