This is the spouse of someone with significant ME/CFS. It is well known that bacteria is transferred between people in the same household unit.

• Kisses transfer 80 million bacteria [2014 Study]
• Cohabiting family members share microbiota with one another and with their dogs. [2013]
• Interplay of personal, pet, and environmental colonization in households affected by community-associated methicillin-resistant Staphylococcus aureus. [2019]
• Household Transmission of Clostridium difficile to Family Members and Domestic Pets. [2016]
• Environmental Contamination in Households of Patients with Recurrent Clostridium difficile Infection. [2016]

This raises all sorts of questions — which I am not interested in exploring… “For better or worse, in sickness and in health”

My wink wink suggestion for microbiome issues has been “Snog a lot of pretty young healthy things as the best probiotic” — my wife does not agree…..

Comparison between Samples

The first step that I did was to verify that all samples used the same reference sticks. This means clicking this for each sample first.

This person has processed FASTQ data thru both BiomeSight and OmbreLabs. I am using OmbreLabs data below. Using reference tables uploaded in 2023.

Criteria	6/8/2022	8/4/2022	9/6/2022	10/26/2022
Lab Read Quality	2.1	3.8	3.6	8.3
Bacteria Reported By Lab	534	774	721	775
Bacteria Over 99%ile	10	3	2	6
Bacteria Over 95%ile	58	27	24	22
Bacteria Over 90%ile	99	53	44	50
Bacteria Under 10%ile	25	68	48	127
Bacteria Under 5%ile	13	28	15	77
Bacteria Under 1%ile	5	3	1	16
Lab: Thryve
Rarely Seen 1%	8	14	9	12
Rarely Seen 5%	43	80	60	73
Pathogens	21	34	33	27
Outside Range from JasonH	5	5	7	7
Outside Range from Medivere	13	13	17	17
Outside Range from Metagenomics	9	9	9	9
Outside Range from MyBioma	7	7	8	8
Outside Range from Nirvana/CosmosId	23	23	19	19
Outside Range from XenoGene	44	44	49	49
Outside Lab Range (+/- 1.96SD)	38	39	26	22
Outside Box-Plot-Whiskers	177	202	153	118
Outside Kaltoft-Moldrup	206	257	203	292
Condition Est. Over 99%ile	0	0	0	0
Condition Est. Over 95%ile	0	0	0	0
Condition Est. Over 90%ile	0	0	0	0
Enzymes Over 99%ile	14	18	5	23
Enzymes Over 95%ile	115	105	59	112
Enzymes Over 90%ile	212	192	143	320
Enzymes Under 10%ile	63	106	93	266
Enzymes Under 5%ile	29	45	27	141
Enzymes Under 1%ile	2	2	0	8
Compounds Over 99%ile	37	36	31	119
Compounds Over 95%ile	289	288	275	281
Compounds Over 90%ile	372	381	361	385
Compounds Under 10%ile	288	255	235	298
Compounds Under 5%ile	192	159	136	216
Compounds Under 1%ile	37	14	4	31

General Impression

• After the first sample, the next two had improvements but the last one went the wrong way.
  • Too high and Too low reduce for 2 samples and then increased
  • Too high or too low for Enzymes were the highest for the last sample
• Most of the third party ranges were constant for the first two samples and most got worst for the last two samples.
• Compounds are much less indicative of issues.
• Special Studies are sensitive to lab quality,
  • 6/8/2022 4-14%, top items: ME/CFS without IBS, Poor gut motility, Cold Extremities
  • 8/4/2022 5-17%, top items: ME/CFS without IBS, Poor gut motility
  • 9/6/2022 4- 18%, top items:  ME/CFS without IBS,  Easily irritated
  • 10/26/2022 7 -22%, top items: General: Fatigue, ME/CFS without IBS

ME/CFS without IBS is a consistent top item and we see that the percentage is increasing.

Proposed Approach

Unlike many samples, we see distinct deterioration in several 3rd party criteria. For many samples, there is no change between samples. We will include those in the consensus, namely:

• JasonH
• Medivere
• MyBioma
• Xenogene

It is interesting to note that one 3rd part criteria improved: Nirvana. To this, we do our usual:

• Lab ranges
• Box-Plot-Whiskers
• Kaltoft-Moldrup

The net result will be more bias to those in the 3rd party criteria cited above. Another way of stating that, we will emphasis more that which everyone agrees are most concerning.

The top suggestions (easily obtained):

• Grapefruit seed extract (studies suggests that the preservative used is the active ingrediant)
• glutamate
• lactobacillus casei (probiotics)
• lactobacillus gasseri (probiotics)
• Peanut
• polyphenols

The top avoids are:

• berberine
• stevia
• Slippery Elm
• lactobacillus rhamnosus (probiotics)
• cranberry bean flour
• cranberry polyphenols

The downloads are attached:

SimpleSuggestions_I-Download

I_ConsensusDownload

Food Suggestions

We mostly eat pastured meats and vegetables. No cereals and little in the way of carbs or even fruit. I used to eat linseed crackers in the USA, but here I eat buckwheat instead. Here in Spain we switched from wild Alaskan salmon, to seasonal, local, small blue fish, like mackerel, sardines, etc. Added Rabbit and can eat a lot more quality raw cured pork, if we want to. I have always enjoyed natural wine and Spain has plenty of it. Fresh made coffee and 100% cocoa. Raw goat, sheep and cow’s milk are also available and I do enjoy them with some regularity.

I used the latest sample with the Kaltoft-Moltrup Normal Ranges. The top suggestions are each because of different nutrients that appear significant with Fiber, total dietary and Magnesium, Mg being a common theme.

• Bean, red kidney, canned, drained: Resistant starch, Stachyose
• Grains, oat bran, dry: Fiber, total dietary, Tryptophan, Magnesium, Mg
• Garden peas, dry, raw: Fiber, total dietary, Magnesium, Mg,
• Grains, rye: Fiber, total dietary, Magnesium, Mg, Proline, Betaine

On the avoid list we have at the bottom:

• Kidneys: High in Vitamin B-12, Selenium, Se, Riboflavin, Cholesterol
• Common bean [White], whole, raw: Kaempferol 3-O-glucoside, Coumaric acid
• Wheat Flour (refined/fortified/sifted packaged), raw: Folic acid

Remember, foods are filtered to the nutrients that are above typical levels for foods containing the same nutrients. The goal is to reduce the intake of nutrients that have been identified to shift things in the wrong direction.

For most people, if you say reduce folic acid in your diet — most people will not have a clue. The purpose of the food suggestions is to translate a precise item into common foods.

Note: If a food in your diet is not in the list then we deem it as neutral. For example: there are 24 variety of rabbit in the food database, only one shows up in the suggestions from the sample, Rabbit, meat, raw, Oryctolaguscuniculus, (Nyama ya kalulu), which suggests to keep eating rabbit. Similarly for milk, the two that shows up are Milk with Cow’s blood (from Africa) of 626 entries for milk.

The video below may help understand Food Suggestions better.

A reader asked me to look at these and other antivirals for Myalgic encephalomyelitis/chronic fatigue syndrome :

“I hope your 2023 is off to a healthy start. I was wondering if you could look into how Paxlovid and similar protease inhibitor-style antivirals impact the microbiome.

I got Covid around Christmas and was prescribed Paxlovid. To my surprise, not only did I immediately feel better Covid symptom-wise, but there were many other positive changes.

My brain fog and fibromyalgia-like symptoms improved quickly and drastically. Unfortunately, these changes did not last very long after finishing my course of Paxlovid.

A similar thing also happened to me years ago when I got influenza A and was prescribed Tamiflu.

Also, anecdotally, from Twitter and Facebook groups around CFS, I know I’m not the only one to have this experience with Paxlovid.

There is also at least one trial underway testing the use of Paxlovid in Long covid patients.

Or perhaps it could also relate to the additional antiparasitic and/or anti-inflammatory actions of some antivirals?

Very curious to get your take and expertise on how this might be microbiome related.”

From a reader

Conceptual Model

It is well documented that virus changes the microbiome (see this list 20+ studies for COVID). A possible reason is that the virus wants to increase substances it needed to reproduce and decrease the substances that inhibits it. This is done by chemical signaling — the virus sends bogus messages to the microbiome.

By reflection, it is likely that antivirals also change the microbiome – possibly by reversing the changes done by the virus. Likely along the same mechanism.

” a viral infection usually results in substantial perturbations in the commensal microbiota, causing dysbiosis in the host, which may in turn further affect viral infectivity.” [2019]

“HCV infection alters the gut microbiota, whereas intestinal dysbiosis induces an underlying inflammatory state.” [2023]

For some literature on this – note that this has only become of interest in research very recently:

• Role of Microbiota in Viral Infections and Pathological Progression [2022] (digram below)
• The Interaction Between Viruses and Intestinal Microbiota: A Review [2021]
• Viral Infections, the Microbiome, and Probiotics [2021]
• Intestinal Microbiota-A Promising Target for Antiviral Therapy? [2021]
• How the gut microbiome regulates host immune responses to viral vaccines [2019]
• The Commensal Microbiota and Viral Infection: A Comprehensive Review [2019]

Past Studies of Antivirals and ME/CFS

I have covered some in some past posts:

• Valacyclovir, EBV and CFS [2016]
• Valganciclovir antiviral and CFS [2016] 21% improved
  • Valganciclovir, HHV-6, EBV and CFS [2017]
• Also see Viral Reactivation and the Microbiome [2020]

Valacyclovir has information available on the microbiome impact. For other antivirals I was not able to find new studies in the ME/CFS context

What was interesting is for a condition that is comorbid, Sjögren’s syndrome

• Microbiota dysbiosis in primary Sjögren’s syndrome and the ameliorative effect of hydroxychloroquine [2022]

Antiviral Impact on Microbiome

“The use of antiretrovirals caused a significant impact on the individuals intestinal microbiota” [2007]

• Influence of hepatitis C virus eradication with direct-acting antivirals on the gut microbiota in patients with cirrhosis [2018]
  • Enterobacteriaceae, Enterococcus, and Staphylococcus was decreased 
• Short-term high-dose gavage of hydroxychloroquine changes gut microbiota but not the intestinal integrity and immunological responses in mice [2021]
• Altered Gut Microbiome under Antiretroviral Therapy: Impact of Efavirenz and Zidovudine [2021]
• Raltegravir:
  • Gut microbiota alterations after switching from a protease inhibitor or efavirenz to raltegravir in a randomized, controlled study [2023]  Prevotella 9 (higher), Phascolarctobacterium and Bacteroides (Lower)

Bottom Line

Antivirals likely have antibiotics like effects on the microbiome. This is documented above. The problem is a lack of studies on which bacteria are impacted. This gives it uncertainty for being effective for any specific individuals.

My wish is that for any long term studies using these for Long COVID or ME/CFS is that microbiome samples be done before after and then 3 months after treatment stops. This would provide concrete information that can be applied at an individual.

My gut feeling is that a single course will not be sufficient for remission. I would suggest following the pattern of rotating and pulsing the antivirals which has helped. This could be combined with appropriate antibiotics. For those not familiar with this pattern:

• Once a month take a course of antiviral or antibiotics (7-14 days) and then nothing for the rest of the month
• Next month take a different one

There are several studies showing that this pattern is more effective than continuous. The conceptual model is that you disturb the bad bacteria and give a chance for the good bacteria to attempt a recovery. The survivors of the bad ones slowly regrow, changing antibiotics or antiviral will typically reduce these survivors because the new substance mechanism is different (so the antibiotic-resistance genes that the survivors had, may not work anymore).

More Coming…

“Thanks, Ken! Just saw the posted version. It won’t be perfect, but I do have a sample about a month before I got Covid and have one on the way, which will be sampled about two weeks after finishing Paxlovid. Not sure you’ll be able to glean anything from that specific test, but worth a shot.”

In discussion with readers, interest in non-drug treatment of mast cell and histamine issues is very high. Trying to get traction with the microbiome has not been successful.On how to use Half-Life, see Half-Life: Not the game but supplements! For Arginine and Glutamine, 100mg of each every hour is suggested.

Dosages: Are the maximum deemed safe by an authority, not recommended dosage

• Cinnamon: (Cinnamomum cassia): Dosage Information, Half life 6.7 hours
  • Cinnamaldehyde is the main mediator of cinnamon extract in mast cell inhibition [2015]
  • Cinnamon extract inhibits degranulation and de novo synthesis of inflammatory mediators in mast cells [2013]
  • Cinnamon extract reduces symptoms, inflammatory mediators and mast cell markers in murine IL-10(-/-) colitis [2016]
  • Cinnamon reduces inflammatory response in intestinal fibroblasts in vitro and in colitis in vivo leading to decreased fibrosis [2017]
• Resveratrol (Grape Seed Extract) Half Life 3 hours. Dosage: 2gm/day
  • Resveratrol Treatment Prevents Increase of Mast Cells in Both Murine OVA Enteritis and IL-10^-/- Colitis. [2017]
  • Resveratrol inhibits IL-33-mediated mast cell activation by targeting the MK2/3-PI3K/Akt axis. [2019]
  • Resveratrol Is a Natural Inhibitor of Human Intestinal Mast Cell Activation and Phosphorylation of Mitochondrial ERK1/2 and STAT3. [2021]
• Black Pepper (Piper Nigrum) Half life: 15 hours, 420mg/day
  • Piper nigrum extract ameliorated allergic inflammation through inhibiting Th2/Th17 responses and mast cells activation.
• Arginine and Glutamine Arginine: 6gm/day, 2 hours. Glutamine: 1 hour, 30gm/day
  • Combined arginine and glutamine decrease release of de novo synthesized leukotrienes and expression of proinflammatory cytokines in activated human intestinal mast cells [2013]
  • Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohn’s patients in association with changes in nuclear factor-kappaB and p38 mitogen-activated protein kinase pathways. [2008]
• Luteolin 400 mg/day, 5 hours
  • Luteolin inhibits myelin basic protein-induced human mast cell activation and mast cell-dependent stimulation of Jurkat T cells. [2008]
  • Mast cells, T cells, and inhibition by luteolin: implications for the pathogenesis and treatment of multiple sclerosis. [2007]
  • Impact of polyphenols on mast cells with special emphasis on the effect of quercetin and luteolin. [2018]
• Quercetin: 2gm/day, 24 hours
  • Quercetin is more effective than cromolyn in blocking human mast cell cytokine release and inhibits contact dermatitis and photosensitivity in humans. [2012]
  • Quercetin and Resveratrol Differentially Decrease Expression of the High-Affinity IgE Receptor (FcεRI) by Human and Mouse Mast Cells. [2022]
  • Inhibitory effect of quercetin on tryptase and interleukin-6 release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. [2006]
  • Inhibitory effect of quercetin on tryptase and MCP-1 chemokine release, and histidine decarboxylase mRNA transcription by human mast cell-1 cell line. [2006]
• Taxifolin 460 mg/day, 1.3 hours
  • Inhibitory effect of taxifolin on mast cell activation and mast cell-mediated allergic inflammatory response.
• Probiotics
  • See this list or probiotics for allergies

Reflection into the Microbiome

Most of the items above are modifiers on Microbiome Prescription. An interesting experiment is to see which bacteria/taxa are modified in common with the above. Below are the taxa that occurs 6 or 7 times for the above 7 items.

Taxa Name	Rank	Impact	Times Shared
Bacteroidaceae	family	Decreases	7
Lachnospiraceae	family	Major Decrease	6
Desulfovibrionaceae	family	Major Decrease	6
Clostridiaceae	family	Decreases	6
Bacteroides	genus	Decreases	7
Faecalibacterium	genus	Increases	6
Ruminococcus	genus	Decreases	6
Desulfovibrio	genus	Decreases	6
Roseburia	genus	Decreases	6
Eubacteriales	order	Decreases	6
Bacteroides xylanisolvens	species	Decreases	7
Bacteroides caccae	species	Decreases	7
Bacteroides ovatus	species	Decreases	7
Bacteroides uniformis	species	Decreases	7
Bacteroides thetaiotaomicron	species	Decreases	7
Phocaeicola vulgatus	species	Decreases	7

Items that are marked decreases, are likely bacteria you may want to reduce if you have mast cell issues. Faecalibacterium is the one bacteria that you want to increase.

Applying to your microbiome sample

On the [Research Feature] tab. Find this section and click #2

See Video above for the rest of the steps

As always, review your plan with your knowledgeable medical professional before starting. Some substances may be inappropriate for other medical constraints.

This week I have been pinged by several people with ME/CFS who have seen drops in Saturated Oxygen Level (SO₂) during the day. One model of many symptoms of ME/CFS (brain fog, easy fatigue) is that of diminished oxygen deliver and reduced products clearance (like CO₂ and Lactic Acid). This reduction of oxygen can be due to many causes: Coagulation, Inflammation, Hemoglobin (iron) disruptions, etc.

Long COVID: This also applies here, “Tiny, Menacing Microclots May Explain Long COVID’s Symptoms“

People who follow me knows, know that I prefer to work from facts, models and objective measurements. Saturated Oxygen Level (SO₂) gives us an objective measurement. Personally, my wife and I use a smart watch that records my (SO₂) and other factors every 10 minutes. The data has been helpful to us to triage some events — it is not a Star Trek Tricorder, but better than speculation.

Importance of Half Life

What is called half-life is actually critical for dosage size and timings. MDs prescribing drugs specify one tablet a day, two tablets every 12 hours, a tablet every 8 hours; are based on half-life typically.

What is half-life? It is simply the time it takes to reduce the level in the body to half of the prior amount.

This is not always simple, it takes time to get the supplement or drug into the body as the following quote indicates:

“In healthy volunteers who have taken oral doxycycline, the maximum doxycycline plasma concentrations (C_max) of 1.5 to 7.0 μg/ml are usually reached within 3 h, and the drug has a half-life of 14 to 24 h” [2005]

Step One — Find Half Lifes!

This is actually pretty easy, usually typing in the supplement and “half-life” will return answers from the web. For the above people, I assembled a list of possible testing supplements from prior posts on coagulation to see if we can determine the possible mechanism for the SO₂ drop they saw. The purpose is to identify a probable cause which should then be discussed with your medical professionals.

See this post for the literature on these. We want to then find the half-life and the maximum safe dosage. Many of the maximum deemed safe (i.e. used in studies dosages) are listed here.

Supplement	Half Life	Max Dosage
Alpha Lipoic Acid	30 minutes [Full article: Alpha lipoic acid intoxication, treatment and outcome (tandfonline.com)	2400 mg/day (see Src)
Aspirin	3 hours at lower doses (300 to 600 mg), 5 to 6 hours (after 1 g), 10 hours with higher doses [source]	4000 mg/day [Aspirin Dosage – Drugsdb.com]
Grape Seed Extract / Resveratrol	2-5 hours [source]	2000   mg/day
Nattokinase	4-6 hours [source]	14,000   fibrinolytic units/day
Lumbrokinase	8.6 hours [source]	1470   mg/day
Serrapeptase	Could not find	30   mg/day
Boswellia Gum	6 hours	4800 mg/day [src]
Bromelain	6-9 hours	2000 mg/day
Piracetam	5 hours	24000   mg/day
Turmeric	6-7 hours	3000 mg/day
Licorice	3.5 hours	32   g/day
Ginseng	n/a	2000 mg/day
Coenzyme Q10	33 hours	1200   mg/d

As above, there can be time to get it into the body as the following states for CoQ 10.

The T(max) is around 6 h, with an elimination half-life of about 33 h. The reference intervals for plasma CoQ10 range from 0.40 to 1.91 micromol/l in healthy adults. With CoQ10 supplements there is reasonable correlation between increase in plasma CoQ10 and ingested dose up to a certain point. Animal data show that CoQ10 in large doses is taken up by all tissues including heart and brain mitochondria. Coenzyme Q10: absorption, tissue uptake, metabolism and pharmacokinetics – PubMed (nih.gov)

This is a useful exercise to do for ALL OF YOUR SUPPLEMENTS. This will answer the question, should you do one mega dose a day or 4 small dosages thru the day or even 6 or 8 small dosages per day – to get the best results. You want to maintain a reasonable level in your body for the whole day.

One possible strategy

There are many possible approaches, my preference here would to start with the longest half life and work down. This leads to the following suggestions (to be discussed with your medical professional)

• CoQ10: 300mg day 1, 600 mg day 2, 900 mg day 3, then 1200 mg/day for at least 2 weeks.
  • 4 capsules per day for some products
• Bromelain: : Given the half life, I would start with 1 capsule every 12 hours (typically 500mg), doubling the dosage on the second day and then keep repeating for the rest of the week
• Lumbrokinase: Given the half life, I would start with 1 capsule every 12 hours, doubling the dosage for the next 4 days keep repeating for the rest of the week
• etc

You want to identify the substance that hints at the source, then get your MD involved. Do not try all of them at once. Introduce one item a week and see what the response is. Personally, I did the Aspirin route which had me running up and down the walls after 7 days — that response persuaded the MD to order the Hemex Lab Coagulation Panels which identified issues. That lead to appropriate treatment.

For the short half-life items, You want to take a SO₂ measurement no longer than the half-life. For Alpha Lipoic Acid, the typical capsule is around 300 mg, so I would go for one capsule every hour for 4 hours and monitor the levels for at least 6 hours. This will keep the concentration at a reasonable level. Going above the maximum dosages has significant risk. This is an example for ALA, Alpha lipoic acid intoxicatıon: An adult [2018]. As always, have your plan reviewed by your medical professional before starting.

Remember: Record in Excel or other product your base line — the daily or weekly pattern before you start. Keep up the recording of SO₂ as you walk thru the substances. For me, having a smart watch that does it makes it so so easy with awesome data to show my MD.

The Unique Possibility of Symptom Treatment Resolving the Cause

My model of coagulation issues is simple: some group of bacteria are dumping chemical signals into the body that triggers one or another form of coagulation. Why would they be doing that? Survival! These bacteria prefers a low oxygen environment so they are taxa-forming your body for their needs. Increasing the oxygen level in the body will typically inhibit these bacteria – but may not be enough to suppress them. The use of other substances (in the personal experience that I cited above, following Cecile Jadin’s “Occult Rickettsia” protocol of rotating antibiotics) may be needed to suppress these troublesome bacteria, to “rid me of this meddlesome taxa”. Note: The virus or bacteria that trigger the illness is unlikely to be the meddlesome ones, rather, other bacteria that saw opportunity in its disruptions of the body and exploited it. I believe these bacteria are seen in stool microbiome samples.

The two videos below are intended as quick introductions to the microbiome prescription site. The site is dynamic with continuous changes of data available and being used.

16s Samples

This covers sites that provides comprehensive reports on your microbiome. The better reports typically report on over 500 different bacteria from a sample.

Lab/Processor	Low	Typical Count	High	Samples Uploaded
AmericanGut	73	156	213	18
BiomeSight	11	572	1305	1635
BiomeSightRdp	279	573	862	15
CosmosId	6	436	705	36
es-xenogene	5	761	5225	24
Medivere	530	721	934	7
Microba	53	126	186	21
OmbreLabs/Thryve	185	671	2238	1241
SequentiaBiotech	166	313	460	36
uBiome	6	249	589	814

Statistics at the start of January 2023

Older Labs

These are older technology and often are focused on a small number of bacteria. Often the focus was based on what was deemed significant 10 or even 20 years ago.

Lab Name	Samples
Viome (No objective measures)	5
All Taxonomies from tests	67
Medivere: Gesundsheitscheck Darm (16s Limited)	15
GI360 Stool (UK)	29
Medivere: Darn Magen Diagnostik (16s Limited)	15
All Bacteria [Family] Reported	25
Smart Gut (ubiome 16s – Limited Taxonomy)	2
GI EcologiX (Invivo)	19
GanzImmun Diagnostics AG Befundbericht	14
DayTwo	8
GanzImmun Diagnostic A6 (cfu/gm)	80
Nordic Laboratories	2
InVitaLab (cfu/gm)	3
Biovis Microbiome Plus (cfu/g)	18
Diagnostic Solution GI-Map (cfu/gm)	498
Metagenomics Stool (De Meirleir) (16s Limited)	4
Genova Parasitology (cfu/g)	4
Verisana (cfu/ml) aka (kbe/ml)	2
Medivere: Darm Mikrobiom Stuhltest (16s limited)	12
Genova Gi Effects (cfu/g)	116
Kyber Kompakt (cfu/g)	2
All Bacteria [Genus] Reported	188
Bioscreen (cfu/gm)	13
NutriPATH	12
Gut Zoomer (vibrant-wellness)	6

New Food Features

This feature was added because many of the suggestions were for flavonoids or other items that may or may not be available as supplements. Most people do not know what is in different foods, especially items you are wishing to avoid. The intent is to allow a more comprehensive and rich diet to be developed by users.