This is different than the body’s Circadian Rhythms. My experience is that it depends on the probiotic — some probiotics taken at bed time will drop me into deep sleep within 10 minutes; other probiotics taken at the same time will keep me wide wake until 3am in the morning — bummer. Why, the probiotic produces enzymes which interacts with the body and the mind. The enzymes vary between probiotics.
This posts reviews some of the literature and attempts to improve mine, and hopefully yours, understanding of the Circadian Rhythm of bacteria with it’s impact on when certain supplements and probiotics should be taken during the day.
There exists a bidirectional circadian interaction between the host and its gut microbiota, and potential circadian orchestration of both host and gut microbiota in response to invading pathogens. In this review, we summarize what is known about these intestinal microbial oscillations and the relationships between host circadian clocks and various infectious agents (bacteria, fungi, parasites, and viruses), and discuss how host circadian clocks prime the immune system to fight pathogen infections as well as the direct effects of circadian clocks on viral activity
This may account for items like night-sweats, for example, my sleeping body temperature is much higher than my usual daytime temperature.
The Literature
“Conditions of dysbiosis have been linked to circadian rhythm disruption, metabolic alterations, and release of neurotoxic products, all contributing to neurodegeneration.” [2023]
“the gut microbiota can influence the host circadian rhythm by a variety of mechanisms including through interacting with the host immune system. The intricate and complex relationship between the microbiota and their host makes it challenging to disentangle host behaviors from bacterial circadian rhythms and clock mechanisms that might govern the daily oscillations observed in these microbial populations.” [2023]
“Misalignment of the clock can cause obesity, which is accompanied by reduced levels of the clock-controlled, rhythmic metabolite NAD+. Increasing NAD+ is becoming a therapy for metabolic dysfunction; however, the impact of daily NAD+ fluctuations remains unknown.” [2023]
Unconjugated bile acids regulate the amplitude and periodicity of circadian gene expression in the ileum, colon, and liver
High-fat diet
Impaired central and hepatic circadian clock gene expression Dampened circadian oscillations of gut microbiota Altered microbial diversity
Time-restricted feeding
Increased gut microbial diversity Reduced total cholesterol and triglyceride levels
Altered light-dark cycle and mutation of the Clock gene [Bmal1]
Microbiota dysbiosis: increase in proinflammatory bacteria and decrease in anti-inflammatory bacteria Causes dysbiosis
Germ-free mice receiving stool from jet-lagged humans
Enhanced weight gain -Higher blood glucose levels after oral glucose challenge
Some Basic Visuals
The following illustrate the difference between day time and night time. “The endogenous clock anticipates the daily fluctuation in the risk of infection inducing a stronger immune response at the beginning of the active phase of the light/dark cycle“. One common immune response is histamine / mast cells. This is seen in this study The Circadian Clock Drives Mast Cell Functions in Allergic Reactions [2018] which states: Allergic conditions such as asthma or allergic rhinitis have historically shown circadian bias as the severity of symptoms is exacerbated between midnight and morning time and exhibits prominent 24-h variation.
Needless to day (I hope needless), microbiome samples should be taken at the same time of day and preferable on the same day of the week (since shifts between a work day and a day of rest could be significant).
The earliest use of antibiotics for treating ME/CFS that I am aware of, dates from the late 1990’s with articles in Journal of Chronic Fatigue Syndrome (and conference reports prior)
My remission from ME/CFS was done by combining C.L. Jadin protocol with Dave Berg anticoagulant protocol.
Overview of results
First, let us show the numbers and then talk about them. It is clear that there are significant changes. There are a lot of dimensions to consider.
Criteria
2-Mar
9-Mar
21-Mar
3-Apr
16-Jun
Shannon Diversity Index (Percentile)
85.2
79.0
99.8
72.4
16.0
Simpson Diversity Index (Percentile)
72.6
63.4
64.4
77.0
91.4
Chao1 Index (Percentile)
65.7
31.2
77.2
62.9
7.9
Lab Read Quality
8.9
8.7
6
4.5
4.4
Bacteria Reported By Lab
654
533
725
585
389
Bacteria Over 99%ile
2
4
30
11
24
Bacteria Over 95%ile
13
10
70
33
38
Bacteria Over 90%ile
25
23
103
63
55
Bacteria Under 10%ile
287
213
123
113
140
Bacteria Under 5%ile
253
173
66
48
96
Bacteria Under 1%ile
219
135
17
8
46
Lab: BiomeSight
Rarely Seen 1%
13
1
38
5
6
Rarely Seen 5%
28
9
107
17
29
Pathogens
36
31
50
40
36
Outside Range from JasonH
6
6
9
9
8
Outside Range from Medivere
15
15
22
22
22
Outside Range from Metagenomics
7
7
9
9
9
Outside Range from MyBioma
5
5
6
6
6
Outside Range from Nirvana/CosmosId
26
26
18
18
15
Outside Range from XenoGene
28
28
46
46
42
Outside Lab Range (+/- 1.96SD)
6
8
56
17
27
Outside Box-Plot-Whiskers
44
36
124
70
67
Outside Kaltoft-Moldrup
233
169
207
137
170
Condition Est. Over 99%ile
0
0
13
10
48
Condition Est. Over 95%ile
1
0
24
35
75
Condition Est. Over 90%ile
2
2
34
55
84
Enzymes Over 99%ile
0
0
347
606
957
Enzymes Over 95%ile
7
0
635
970
1145
Enzymes Over 90%ile
24
28
746
1159
1228
Enzymes Under 10%ile
506
515
561
237
245
Enzymes Under 5%ile
378
360
422
143
174
Enzymes Under 1%ile
194
166
120
52
94
Compounds Over 99%ile
0
0
225
215
617
Compounds Over 95%ile
2
0
355
410
732
Compounds Over 90%ile
8
11
441
520
778
Compounds Under 10%ile
1243
986
1105
902
822
Compounds Under 5%ile
1156
926
1032
856
796
Compounds Under 1%ile
1115
875
936
828
767
Next are the percentages by percentile which I noticed tend to have over representation with ME/CFS and Long COVID in the 0-9 percentile. We see this pattern at the start, with improvement and then a bounce back to high numbers.
2-Mar
2-Mar
9-Mar
9-Mar
21-Mar
21-Mar
3-Apr
3-Apr
16-Jun
16-Jun
Percentile
Genus
%
Genus
%
Genus
%
Genus
%
Genus
%
0 – 9
65
40%
51
36%
28
15%
29
19%
35
36%
10-19
13
8%
16
11%
36
19%
23
15%
9
9%
20 – 29
11
7%
16
11%
20
11%
23
15%
14
14%
30 – 39
5
3%
9
6%
17
9%
17
11%
4
4%
40 – 49
13
8%
10
7%
14
8%
11
7%
5
5%
50 – 59
12
7%
8
6%
10
5%
8
5%
3
3%
60 – 69
12
7%
9
6%
6
3%
14
9%
1
1%
70 – 79
12
7%
3
2%
10
5%
6
4%
5
5%
80 – 89
10
6%
10
7%
15
8%
9
6%
7
7%
90 – 99
11
7%
8
6%
30
16%
15
10%
15
15%
Total
164
140
186
155
98
2-Mar
2-Mar
9-Mar
9-Mar
21-Mar
21-Mar
3-Apr
3-Apr
16-Jun
16-Jun
Percentile
%
Species
%
Species
%
Species
%
Species
%
Species
0 – 9
41%
94
43%
79
13%
40
17%
36
21%
31
10-19
6%
14
9%
16
15%
44
13%
28
9%
13
20 – 29
8%
18
9%
16
13%
39
12%
27
15%
22
30 – 39
3%
7
5%
10
10%
29
10%
22
8%
11
40 – 49
7%
17
4%
7
7%
20
8%
17
6%
9
50 – 59
9%
21
5%
9
7%
22
6%
12
5%
7
60 – 69
6%
14
8%
14
3%
10
6%
14
6%
9
70 – 79
8%
18
4%
7
6%
19
7%
15
6%
9
80 – 89
6%
13
8%
15
8%
23
8%
17
10%
14
90 – 99
5%
12
6%
11
19%
57
13%
29
14%
21
Total
228
184
303
217
146
The Events Around the above Samples
2023-03-02 (baseline)
2023-03-09 (during a stomach bug)
2023-03-21 (during a “Level 1” remission while taking Amoxiclav. Level 1 = all symptoms gone. Felt great. Had started Amoxiclav on the morning of 3/20, this sample was taken after 3 doses around 3pm)
2023-04-03 (4 days after stopping Amoxiclav, was on Doxycycline)
2023-06-16 (During 2nd round of Amoxiclav when I felt really bad)
The microbiome results definitely reflected the Level 1 remission on 3-21. The low percentile genus and species percentage almost made it to the target level of 10% from the prior 40%! The Shannon Diversity Index was awesome (the higher the better!).
I have often described correcting the microbiome as being similar to sailing a sailboat along a coast line. Depending on wind and tide, there may be a lot of course changes required. I am curious on the ranking of Amoxiclav[amoxicillin] and Doxycycline with these samples. The numbers below suggests that going on to Doxycycline may have been a poor choice. On the 2nd round of Amoxiclav, it was at just 35% of the highest value recommendation versus 70% on the 1st round.
Note that rifaximin and rifampicin are in the same family and used by some ME/CFS specialists. Imipenem shows up often with ME/CFS samples — but since it is intravenous, not the easiest to get on an ongoing basis.
Take Away and Reflections
This project main purpose was to show that remission can be triggered by antibiotics to another generation of people suffering from ME/CFS. The remission on 21-Mar demonstrates this to be correct both subjectively and objectively (Microbiome data — specifically Shannon Diversity Index and Percentages in different percentiles for Species and Genus). I should emphasis that both of these measures are multi-bacteria measures and do not support the common myth that ME/CFS is caused by a single bacteria.
The critical issue is maintaining remission. How do keep the microbiome where it should be. I often use analogies of cities because we are talking about a city of bacteria. To stop riots and looting in the streets you send in the National Guard (antibiotic). The city is back to normal. The causes of the the riots are still there. Typically lack of opportunities, neglect, etc. in these same ghettos. You must address these other issues. A repeat of sending in the National Guard may have the same effect as the first time OR very different effects – the same can be said for using the same antibiotics.
With bacteria we have two “radical organizations in the ghetto” — The Antibiotic resistant and the Resistors. For example, the bacteria that survive learnt how to avoid the National Guard and proceed to share that skill to other bacteria. Instead of a wall of shields pushing the rioters back, Molotov cocktails rain down on the troops from above.
Another analogy is that the gut is a pendulum. The antibiotics, probiotics and other items pushes the gut towards the equilibrium position! There is great joy! The gut is centered… At this point, many people go down the wrong reasoning path — “Keep doing more of the same to stay in remission!“. Remission is lost and the momentum pushes the guts out to the other side!!! You pushed out one devil and seven more devils return! (Math 12:43-45)
The key is to dampen down the swing so there is less and less swing. My personal opinion is that Cecile Jadin’s protocol using antibiotics for only 7 days each month is a very effective way of dampening the pendulum gained from decades of experience.
My approach with Microbiome Prescription is to try to address the whole city. Before taking action, we get intelligence on the nature of the city and decide on the appropriate action for a period of time (typically 4-10 weeks). We then update our intelligence (i.e. microbiome test) and pick the next course of action. Actions may include “food kitchens”, “safe injection sites”, “training programs”, “home repairs”, “on the beat policing”, etc.
There are many people who will state that antibiotics gave me ME/CFS. I do not disagree. Antibiotics can also trigger remission — the problem is WHICH antibiotics. Since every person’s microbiome is unique, there can be no universal “best antibiotic” for ME/CFS. Antibiotics must be selected based on the individuals microbiome (which is the path that Microbiome Prescription took) for the best odds of making the right choice.
My Suggestions Going Forward
I am working with C.L. Jadin, M.D., on documenting her current protocol from almost 30 years of experience using antibiotics for ME/CFS. It will be out soon. I am hoping to have that available within a month. One key aspect of her protocol has been pulsing antibiotics using two at a time. There are a few studies showing that pulsing is more effective. Pulsing often means 7 days on and 21 days off.
Looking at Tess’s last sample, I would propose the following to be considered (items that I picked from the consensus suggestions):
Take a 3 week break from antibiotics (Ideally at the end take another sample)
A common pattern of people is “Just give me a pill to fix me, I want to keep my current life style and I am not prepared to make significant life style and diet changes”. My impression is that making those changes is often required. Inertia is a real maintainer of ME/CFS, especially the pendulum inertia when trying to heal.
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 can compute items to take, those computations do not provide information on rotations etc.
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.
In 1994, after two years of a high stress job managing and motivating direct sales groups in my own sales company I quit and I spent 6 months very fatigued, without moving my body very much and staring at the void sitting on my sofa. I could barely lift a glass of water. After the six months I regained strength and I commenced in a new job. Doctor said I had the yuppie flu, gave some vitamins and tests showed I had had epstein-barr viruses.
In 2008 I recall being very fatigued again. And again 6 months secluded at home sleeping 14 hours a day (I have no family in Spain). I could work but I was uneasy and the job was stressful at times,. In 2009 I started to undergo tests in a private clinic, cause the public hospital who was cutting edge at CFS has a a waiting list of years. I wanted to know what I had. Blood samples, screening, mutaflor, some other immune system boosters, etc. Diagnosis 2010: CFS (not Fibromyalgia yet). I started also to attend to conferences and read a lot about my illness (which I don’t do anymore).
In 2016, after years working with fatigue and pain I decided I couldn’t stand it anymore and thought I should care about myself so I went on sick leave for one year. Afterwards I solicited voluntarily leave of absence.
CFS/EM slowly shifted more to Fibromyalgia. I was diagnosed in one of the best public Hospitals in Barcelona (the renowned Hospital Clínic). They gave me advice on doing exercise, not much more.
Now I say I have moderate EM and moderate to severe Fibromyalgia. Depends on the day. I stay at home mainly. IBS, Psoriasis, Costocondritis sometimes, eye problems, dizziness. muscular problems and stiffness, etc. I am going to a Quiropractic for many years. With an electric bike I can do some miles.
I see there are a lot of supplements in Biomesight, It would be highly appreciated if you could give some insight of my Biomesight results and how to get started changing my gut’s microbiome (food, supplements, etc).
Clarity on Suggestions from Biomesight
I do not know how Biomesight derive their suggested supplements. Many microbiome providers use nutritionists who often suggest generic “healthy” supplements. In other cases, they have found a study for a supplement that impacts one bacteria and if you are high or low for that bacteria, suggest that (ignoring what that same supplement will do to other bacteria!). I would love to see a detailed blog from Biomesight on how they determine appropriate supplements to suggest.
Microbiome Prescription uses almost 1.9 million facts(i.e. X substance modify Y bacteria) and then consider all interactions that a supplement has on all bacteria of concern.
Analysis
First, we will look for a common fingerprint for ME/CFS and Long COVID: Over representation of bacteria in the 0-9%ile. We have a very strong match shown below. The numbers in each range should be about the same number for a healthy microbiome.
Looking at Dr. Jason Hawrelak Recommendations we find it at 75.3%ile, indicating issues with the following being most concerning:
Faecalibacterium prausnitzii well below his low limit. This bacteria is deemed anti-inflammatory [2008] and thus a contributor
The Potential Medical Conditions Detected using the US Library of Medicine studies show what you reported and a few other items of concern (Asthma, Colorectal Cancer [possible false positive], etc)
Fibromyalgia 96%ile
Chronic Fatigue Syndrome 96%ile
Inflammatory Bowel Disease 94%ile
Gastroesophageal reflux disease (Gerd) including Barrett’s esophagus – 97%ile
Going Forward
First a quick video on the process
I did the “Just give me suggestions” followed by individual sets of suggestions for the four above item resulting in 8 sets of suggestions done with different criteria to select critical bacteria (See video). We then use consensus to identify the items most likely to help. This is a way to improve results in the face of many unknowns.
Probiotics (usually I suggest take 1 probiotic for 2 weeks at sufficient dosage (see this supplement dosages link) and then rotate to the next one on the short list, then repeat.
Antibiotics (if you have a willing MD) — one course then 3 weeks off, then a course of a different one. All of the ones below has been used by specialists for ME/CFS or FM
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.
This is a follow up to the January 2022 post, IBS + BioNTech COVID Vaccine -> ME/CFS? For discussion on vaccination changing the microbiome see that post (ANY thing that changes the microbiome has a risk of cascading into ME/CFS — an innocent kiss could result in result in the kissing disease( Infectious mononucleosis) which is usually Epstein-Barr virus and well associated with ME/CFS!).
[Revised: Jul 27th,2023 There was a mix up on the sample for some analysis]
The Request
One biomesight test failed and then I got Covid again, so I had to wait.
There are some improvements since last time: I can listen to music again. I can play cards with my brother a little bit in the night when it’s quiet. I was also able to breathe freely again while doing most things, but in January I had an exhausting doctors appointment and some improvements were lost.
A few specific questions:
Are the “mold bacteria” you mentioned last time still a problem?
Have there been any important/significant new treatments or scientific findings recently that you are aware of that would help me with my issue (CFS from biontech vaccination)?
Things I am taking continuously right now: Magnesium malate, Coenzyme Q10, Acetyl-L-carnitine, Vit. D+K2, Piracetam.
Analysis
“In one study researchers were able to classify 83% of the ME/CFS patients correctly based on their dysbiosis in gut and increased inflammatory markers in blood as a consequence of microbial translocation”
We have three samples, the first one was at the start (and used in the above post). I mentioned in the earlier post that he had not had the symptoms long enough to be deemed ME/CFS. The table below seems to show that the typical ME/CFS and Long COVID pattern is not an immediate result but is cascaded into over time. The pattern of over representation of the percentage in the 0-9 percentile showed up in subsequent samples. We see agreement with his subjective opinion of improvement and then loss of progress in the numbers below.
Nov 2021
Nov 2021
May 2022
May 2022
Jun 2023
Jun 2023
Percentile
Genus
Species
Genus
Species
Genus
Species
0 – 9
11
10
56
81
43
54
10-19
12
16
15
14
13
16
20 – 29
12
13
15
21
17
11
30 – 39
16
19
12
11
8
18
40 – 49
9
13
21
17
9
13
50 – 59
19
24
15
26
14
14
60 – 69
13
19
15
17
17
19
70 – 79
23
20
12
21
11
11
80 – 89
14
18
14
16
12
12
90 – 99
12
12
9
12
5
14
Shannon Diversity Index
79%ile
83%ile
42%ile
Jason Hawrelak
96%ile
95%ile
56%ile
COVID %ile
83%ile
71%ile
83%ile
The “mold bacteria” is a reference to Prevotella. This often grows excessively when there is mold or fungi. His latest sample had a low percentile, so unlikely to be an issue.
Going Forward
Doing “Just Give Me Suggestions” executes the following four individual approaches:
On the simplified summary (intended for those with severe cognitive impairment) there is a button that takes you to the full details (the consensus report)
This gives a list of 1800+ different items that were evaluated. I am not a medical professional and do not have clinical experience. My choices from this tend to arbitrary but with the following guidance:
To take items should be at least 50% of the highest value (in this case, 553 /2 =277)
To Avoid items should be below 50% of the lowest value (in this case, -541/2 = – 270)
If the person has ME/CFS or Long COVID, and I know from reading the literature that studies found that it helps people, I will tend to pick those items
In general, I will not suggest prescription items because most patients will be stonewalled by their MDs on doing prescription items off label. If I do (because the patient reported having a cooperative MD), I will tend to keep to items documented to help ME/CFS patients.
I then checked what is he taking against the results:
Because the reader is in the “Land of Mutaflor” (Germany), I checked that explicitly in two ways:
Using KEGG Data — it was the top probiotic (but the value was lower than usual)
Using Consensus Data — it was very slightly positive (0.3).
So it does no apparent harm (except on pocket book), and I would consider trying it after the above bifidobacterium because low E.Coli has been reported in studies (16s does not provide data).
Checking KEGG suggested supplements against the consensus, we have the following in agreement:
Remember we are dealing “fuzzy data on sparse data” and use the consensus approach to improve odds of picking things that will actually do positive changes. By comparing KEGG identification of metabolites that appear to be at low level (and thus starving some bacteria) with the same items that will improve the bacteria balance, we add another layer to consensus building for suggestions. One more layer is taking substances shown to help ME/CFS which are not in our database. He appears to be making use of my CfsRemission site for that purpose. Consensus and layered is the most likely to produce good results.
Antibiotics
This person reports a friendly medical professional. So:
There are many antibiotics commonly used with ME/CFS that are over 270, which would be my personal preference.
I would do the first one only. I have a pending post with a video with Cecile Jadin which may be helpful.
To Avoid
This is usually selecting items that are likely to be taken by some. If it is below -270, it should be consider to reduce of eliminate. We have a long list, my arbitrary selections are:
vitamin d – -263, close enough and with feedback on current levels, likely a stop
Q: “Vit D is negative”: My vitamin D is in fact over 150 nmol/l already should I stop?
A: Yes. If a value is negative it is likely that taking it will be shifting things in the wrong direction.
Q: “Grapefruit daily”: I quickly develop food intolerances. Would every 3 days be reasonable?
A: Start with every 3 days, if issues arise, try the supplements. Remember these are just suggestions to be considered and may need to be filtered by your tolerance and costs. This applies to your next question too “The same problem for the herbs: Would every 3 days be enough? Also can I just add multiple herbs to my food or are these also “One thing at a time, no juggling”?“
Q: This might be a dumb question: Is the suggestion all three bifidobacterium in a row, or just pick one of them and then Mutaflor?
A: There are never dumb questions. The sequence is arbitrary. Proceed as you feel comfortable. Bifidobacteria is likely to have a greater effect.
Q: B Vitamins and Amino acids: Also one thing at a time? I know I’m asking this question again, but I am really unsure because if I do all the suggestions in a row it seems it might take like a year..
A: Do them all at once or in groups. The reason for doing things in rotation are for items that bacteria are likely to adapt to (i.e. bacteria resistance). These items are typically probiotics (which produce natural antibiotics), antibiotics and a herbs/spices with significant antibiotic like effects. These are not such items.
Q: My mom suggested me N-Acetyl-L-Cysteine which helped her a lot, and I want to look that up.
Feel free to inspect that list and create your own set of suggestions. These are suggestions only based on your microbiome and computation. For ME/CFS, I try to highlight items seen to have positive effects in studied. You may wish to search CFSRemission for literature on items you decide to try.
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 can compute items to take, those computations do not provide information on rotations etc.
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.
This person gave an extensive history – the microbiome reflects recent events in general so I have skipped most of it because of that.
An analogy may help, bacteria can be viewed as a city, say London or New York. An “event” happens, for example the Irish Potato Famine, or a shortage of labor causing the import of people from the colonies. The culture of the city is challenged. People are displaced and will often push back; fight back. Eventually a new status quo is established — it does not happen overnight, but over years; over decades. Returning to the old ways (London full of Saxons; New York full of tribal Indians) may be dreamt of, but never happens. An infection is a new wave of immigrants into the city. The impact does not always reflect the numbers. A small number of drug traffickers can have a huge impact on a city. This is how I think about the microbiome — a dynamic living city of bacteria that keeps changes over time. Ghettos develop where once stately manors of well-to-do people were.
Recent Back Story
In September of 2022, I had a COVID infection and fever, which caused a significant “crash”. I have been mainly bedridden ever since. Though the severity of symptoms I experience has waxed and waned from then until now, there has not been any significant differences in ability since. My symptoms are varied, and I’ve noted the ones experienced the week I took my sample on Microbiome Prescription. Positively, I have recently experienced a lowering of resting heart rate with regular electrolyte consumption, HR based pacing, NSDR, and diaphragmatic breathing. Starting Low Dose Naltrexone has helped with pain management, and I’ve needed to take less naproxen as a result.
I’ve tried oxaloacetate and pregabalin to no effect, had some significant side effects with duloxetine, and had a severe reaction with no benefits when I tried CBD/THC oil.
An interesting point is that my microbiome seems more similar to those Covid19 “Longhaulers” than to those with ME/CFS. I wonder why that may be, given that I had ME/CFS before my Covid infection?
I view both Long COVID and ME/CFS to be the same condition with one key difference. Long COVID is a recent major disruption of the microbiome. ME/CFS is often an ancient disruption that has evolved into a more stable state. Long COVID is typically an unstable microbiome that has a high rate of change. See this post on ME/CFS outbreak traced to a specific community infection. Some microbiome return to a stable normal state over time (a.k.a. remission). Going back to the cities examples above, Long COVID is akin to the mass migration of African Americans to Chicago after the civil war. ME/CFS is the state of Chicago today.
This person’s back history included:
“Chronically anxious child with perfectionism tendencies” this pattern has been associated with ME/CFS by many. In terms of the microbiome, the stress would have significant impact on the microbiome.
Severe constipation that required hospitalization, again know microbiome shifts. She has taken Polyethylene Glycol regularly. This is known to cause microbiome shifts.
Taking fludrocortisone (fludrocortisone) and duloxetine for several years.
Crohn’s disease, though the biopsies from the digestive tract were inconclusive. Again known microbiome shifts.
What does this mean? There is a massive amount of “microbiome noise” from these medical conditions and significant drugs. This could be classified as a hodge-podge of a microbiome.
Other questions I have regarding my sample:
Based on my sample, is it possible to tell the likelihood I have (or eliminate the possibility I have)…
poor gut motility
MCAS/Histamine issues
Specific intolerances such as gluten or dairy
SIBO
Leaky Gut
Celiac
Basically, can I extrapolate from the data if I may have issues to fix regarding one of the above or if I can say with some certainty that these don’t affect my gut health?
No, it is not really possible to tell the likelihood. The best that you can do is whether you have bacteriaassociated with those conditions. Association main purpose is to augment or suggest additional medical tests. Some examples:
Special Studies:
12 % matchPoor gut motility (your highest was 30% for Long COVID)
Postural orthostatic tachycardia syndrome (0 %ile) 0 of 6
The PubMed one that you are highest in is Colorectal Cancer (with 9 of 38 matches). This some some resemblance to her recent medical history.
Around August 2020, I started experiencing rectal bleeding, abdominal cramping, mouth sores, and rectal prolapse. I had a colonoscopy and endoscopy in Dec. 2020 with general anaesthetic, and it was as if I had been “hit by a truck”. I could barely get out of bed for the next 5 months. I was diagnosed with Crohn’s disease, though the biopsies from my digestive tract were inconclusive…. Some other anomalies found include a potential cyst on my right ovary and a tender and enlarged lymph node near my right armpit. The cyst and fluid sac may just be “the more you look, the more you find”.
I seem to be intolerant to (or not digest very well) dairy products (with or without lactose), processed foods, acidic fruits (such as raspberries, oranges, lemon or pineapple), starchier foods, oils and fats, lentils, onion, garlic, asparagus, almonds, cucumbers, broccoli, tomatoes, chai, rice crackers, etc. With some foods, such as gluten or eggs, it seems to vary as to whether I tolerate it well.
My medications at the time of the sample were:
Low Dose Naltrexone 3mg
Nadolol 40mg
Multivitamin
Vitamin D 2000iu
Vitamin C 500g
Naproxen as needed for menstrual and joint pain
Since then, I’ve added these supplements:
Magnesium Glycinate 90mg TID (total 270mg)
Inulin 1tsp
Align Probiotic 1 capsule
Probiotic 3 1 capsule TID (total 3 capsules)
Tributyrin-x 3 capsules
D-Ribose 5mg
Analysis
Unlike most Long COVID and ME/CFS microbiomes, the percentage in each percentile is well balanced in the percentages in each percentile. This may be due to items like Low Dose Naltrexone and other medication, or her complex medical history. In terms of Shannon Diversity Index, it was high 2.07 / 97.1%ile.
Switching over to Bacteria Deemed Unhealthy, we see a very long list. Some of these are associated with MCAS and allergies. This is a much better signature than the above ones.
Going over to KEGG AI Computed Supplements, we see a long list, much longer than typical. Items over a Z-Score of 2 are strong candidates for taking as supplements. These are chemicals consumed by bacteria or the body and thus suggests starvation of bacteria (with misbehavior likely).
Looking at AI computer probiotics, nothing stood out strongly. Enterogermina (Bacillus Clausii) is the strongest suggestion.
Analysis of What Is Currently Being Taken
The following times were listed above, I did the “just give me suggestions” and the looked at the full detail via the consensus report. Usually the consensus report highest value is around 400; her report went up to 753 and down to -1064. This is far more variation than I usually see!
Low Dose Naltrexone 3mg – GOOD, 496.4 (max was 753.
Nadolol 40mg – GOOD, 496.4
Multivitamin
Vitamin D 2000iu – so so, -15
Vitamin C 500g – positive: 400
Naproxen as needed for menstrual and joint pain — Good 496.4
Magnesium Glycinate 90mg TID (total 270mg) – negative -355
AOR Probiotic 3 – 1 capsule TID (total 3 capsules)
Enterococcus Faecium – so so (-22, -172), to negative
Clostridium Butyricum – negative – 306
Bacillus Subtilis – so so (-19,-48, -315) to negative
Tributyrin-x 3 capsules – so so -12
D-Ribose 5mg – negative -200
Remember: these are fuzzy logic computation based on fragmentary data available from existing studies. In general, readers have reported improvement from the suggestions – but the suggestions are plotting courses in a fog bank… so do not become dogmatic about doing or not doing.
So what is suggested instead?
Well, all of the prescription items above are big thumbs up! 🙂
496 – Acetaminophen, Paracetamol in UK one with each meal for a week and then one a day? Discuss with your MD. The purpose is altering the microbiome, not headache (i.e. off label use)
584 – sucralose – most other sugars are low or negative value
Questions and Answers
Q: It seems that my microbiome is very well balanced, but has many unhealthy bacteria and a much more varied consensus report than usual. With other similar results from others, do you see a common reason or cause for this being the case?
A: I would not call it well balanced. Several measuring sticks show no strong pattern, but given the large number of microbiome affecting things that have happened to you, those events have likely added a lot of noise. The abnormally large number of bacteria deemed unhealthy is the signature thru this noise. This is not a common situation. Most people have just one microbiome affecting thing.
Q: Being in the 0% percentile for POTS seems interesting for me, given that my POTS is still not quite stable. What are the usual reasons for a microbiome not matching the symptoms and diagnosis of a particular condition (especially that I’m only a 12% match for MECFS with/out IBS)?
A: Similar to above, compounding conditions and treatments that alters the microbiome is a multitude of ways. Ideally, we want to see patterns but patterns usually arise from “pure cases”, you are not a pure case, but a highly compounded case.
Q:Given I have the highest association to Colorectal Cancer, how important is this? Is this something I should be looking to screen for or is it of low enough significance to ignore somewhat?
A: In the abundance of caution, I would ask for screening, you have one recognized risk factor with a hint also from your microbiome. Per CDC guidelines (helps persuade MDs) “However, you may need to be tested earlier than 45, or more often than other people, if you have— Inflammatory bowel disease such as Crohn’s disease or ulcerative colitis.” [CDC]
Q.I’m currently taking magnesium mainly as a tool to manage muscle spasms and twitches. Is there a supplement with similar effects that has a better consensus value?
Lactobacillus paracasei is cited [2004] “Lactobacillus paracasei, but not Lactobacillus johnsonii, Bifidobacterium lactis, or Bifidobacterium longum, attenuated muscle hypercontractility.” Unfortunately a negative.
Streptococcus thermophilus and Lactococcus lactis [2022] “Spasm reductions were accompanied by specific gut microbial alterations, including increases in Streptococcus thermophilus and Lactococcus lactis. Mimicking the fecal microbial alterations in a targeted probiotic, we administered these species in a 5:1 ratio. Targeted probiotic administration reduced seizures and improved locomotor activities in control diet-fed animal” – No information, so these two would be my first preference.
From other articles, there appear to be associations of spasm and twitches with mineral imbalances. For example, hypokalemia(low potassium) [2023] – I would suggest explicit testing for mineral balances
If you have a willing MD, I would ask for amoxicillin which is a common antibiotics and has the second highest confidence of having an impact. The top one, Imipenem, is an intravenous β-lactam antibiotic and it’s impact on the microbiome is less certain. Remember, most MDs will only prescribe for acute active infection and a microbiome dysfunction/issues may not be sufficient for them. My next choice would be thyme oil and hesperidin supplements. With the thyme oil — definitely start with a low dosage and expect bacteria to be protesting strongly (often they protest by massive dumping of toxins into the body… they do not go out quietly).
If you try these suggestions and notice changes, I would suggest another test in 8-10 weeks to see what changed and what your next course correction will be.
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.
Microbiome Prescription uses over a million rules to generate suggestions on improving the microbiome and hopefully reduce or moderate autism behavior. All of the sources of the rules are studies on the US National Library of Medicine. Microbiome Prescription also can provide the complete evidence trail for every suggestion! That is, where — precisely– is all of the information coming from — none of it is private personal opinion or speculation.
Cross validation is the process of taking one set of information to generate forecasts or suggestions and then look at a totally independent source of information to see if the forecasts and suggestions are valid, reasonable, and appear to help individuals with the condition. I have done that for several conditions with very good results. NOTE: Everything is generated by code — code that I prefer to improve or correct. I have no personal stake in the suggestion, nothing to defend.
The process is simple: some items may have been tests in trials for autism, some have not. If it has been tried, we see what the result in and provide a link to the study (open data!! no “trust me, I am an expert” hype)
“Binding studies show that both the B. subtilis and human ASLs bind up to 4 mol of APBADP per mole of enzyme tetramer and that both enzymes exhibit cooperativity: negative for B. subtilis ASL and positive for human ASL.” [2008]
Randomized controlled trial of sulforaphane and metabolite discovery in children with Autism Spectrum Disorder [2021] “Sulforaphane (SF), an isothiocyanate from broccoli, is a multifunctional phytochemical that has several demonstrated benefits on cellular processes relevant to ASD, including cytoprotective, antioxidant and anti-inflammatory responses, mitochondrial and synaptic function, neuroinflammation and neuroprotective mechanisms, as previously reviewed”
One item that is complex/questionable – depends on the child’s DNA
The goal / objective of Microbiome Prescription is to make suggestions that are more likely to help than to hurt. That goal seems to be accompanied. A secondary goal is to suggest items that have not been studied but modelling suggests that it may be of benefit to try. We have 5 such items above.
Remember these are GENERIC Suggestions for GENERIC Autism
The results of an individuals microbiome will be different — there are many variants and subsets for Autism. Each variant will tend towards their own set of variations for the microbiome. Using an individual’s microbiome sample will get suggestions unique for them.
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.
The KEGG: Kyoto Encyclopedia of Genes and Genomes provides detail information on the enzymes by strains. These enzymes determine what is produced and consumed. Not 100% guaranteed (enzyme activation depends on multiple item), but sufficient to use Fuzzy Logic on it.
I had taken a first crack at using this information a few years ago without outstanding results, and had marked the option as being deprecated.
This last week, I got this email from a reader
Another experiment , taking 500mg of tyrosine. Old test showed low dopamine and noriepinephrine . Man I feel so much better. My ADD symptoms went away and i can lock in and get so much done. Energy is better. The question is, why does that work so well , I eat meat all the time and protein powder? Why was my dopamine/noriepinephrine low to begin with , what is the cause and how do I fix it so I don’t need to supplement
Open to ideas, thanks!!
My first step was to find the old menu item where estimates for compound produced and consumed are calculated. His level for tyrosine net was very very low. Hence, connecting the dots — we see why the supplement improved things for him.
The second part was more interesting. How to avoid a need to supplement? His levels being very low means looking at the bacteria that consumes and produces it with a goal of changing them.
Update Menu Item
This is on the Changing Microbiome Tab
Clicking it will show the estimates for your microbiome.
As with most things microbiome, the distributions are never normal. To facilitate picking the best items to focus on for experiments. You want a low percentile and a large negative z-score. A positive z-score indicates that the number is above the average (mean) and likely not to be concerned above.
There are 4 items listed that I would suggest experimenting with — by experiment I mean, try taking supplements (one at a time) for 2 weeks each and see if there are any subjective changes. For me the items are:
Phenylalanine
Leucine
Valine
Isoleucine
Clicking on too few will show which bacteria. This may be a blank table.
Clicking too many will show the consumers
You can then hand-picked bacteria that you are interested in altering.
Bottom Line
This is intended to be used experimentally — that is, the suggested supplements should be tested. Ideally with objective measurement, but with the reality of time delays and costs, subjective measurements may be the best that is practical.
If the supplement helps, then (and only then), you should try to alter your microbiome to correct the microbiome imbalance.
For more analysis of ME/CFS and Long COVID see this list.
Percentile’s Percentage
Below are my numbers during a flare — I had the typical over-representation of 0-9%ile seen in most ME/CFS and Long-COVID samples.
After going into Remission, the low percentile counts dropped massively
Alpha Diversity
During Flare
After going into Remission, the two Diversity Index increases significantly. Common belief is that the higher the diversity indices, the better it is for a person. Diversity index typically decreases with age as age related conditions increase.
Dr. Jason Hawrelak Recommendations did not reflect the change. At 98.8%ile during the flare and dropping to 89%ile with remission.
Seeing the Rickettsia spike reminds me of Cecile Jadin’s work from the 1990’s where this bacteria was very frequently identified in ME/CFS patients using specialized tests.
Bottom Line
We have some clear patterns associated with ME/CFS and Long COVID. It is my belief that the microbiome is a very significant player in this condition and that by correcting abnormal shifts by diet, supplements, antibiotics, etc, remission is probable for many. How to correct is very specific to an individual’s microbiome. There is no universal protocol.
Alpha Diversity Indices are not useful in determining how to improve your microbiome. They can be useful to see if your microbiome is improving. Below, I have a table from on long time user of the site below. There was COVID around Jan 2023 and other issues too.
We can see that all of the three indices are moving towards 50%ile, that is typical, overtime. What is ideal for each index is poorly defined. As you can see below — indices averages changes by age so an goal would be to have an index associated with a age younger than you are.
How do we get to this table? Go to Multiple Samples tab and then select Multiple Samples Comparison as shown below.
Then just pick the desired samples. They must all be from the same lab.
Enhancement
On the Research Features tab, we have our new panel. The numbers are now lab specific. The Diversity numbers can be very dissimilar between labs. We have also added information on diversity seen for different self-reported symptoms.
This page can be very interesting to explore. For example Some indices decreases as you age, and other increases. If you want to slow aging (and thus age related medical conditions), you want to work at changing the indices a bit (how is not clear).
For a condition like Long COVID we see that the Shannon Percentile is at 32%ile, i.e. a drop in different species. This matches what is seen with ME/CFS
The Literature
We find some of the above results reflected in study
“age was negatively correlated with .. the Chao index, ” [2018] – which we see above
Bottom Line
None of these indices lead to treatment suggestions. They will be cited in studies on occasion. The lab breakdown by symptoms is likely better data then what will be found in studies — because the distribution is dependent on the lab, i.e. part of The taxonomy nightmare before Christmas…
I think my case is unique and interesting. I have had CFS/ME for 37 years since age 15, but I have been very functional for the most part. I had been worsening over the past 8-10 years and discovered high mold levels 3 years ago in my house. I developed MCAS and related symptoms from the mold. But with treatment I was improving ( See Pre-COVID Thryve sample which is quite good.)
Then contracted COVID in Nov 2021. I had a moderately severe acute COVID illness and did not recover fully, developed Long COVID. Shortness of breath, low o2 sat, palpitations, dysautonomia, insomnia, irritable bladder, cognitive issues much worse than CFS/ME. My GI issues were not too bad though. Diarrhea on and off for several weeks. Gas and bloating that aligned with my MCAS fluctuations. I did have a GI Effects test done during this time (Feb 2022) and it wasn’t too bad (5 score on dysbiosis 0 or 1 on other markers, 2 on inflammation. I know the limitations of that test.
My health steadily improved and as of 2 months ago I was 85% from my pre-COVID health. But contracted respiratory illness, most likely COVID again. Sore throat, congestion, GI issues. Took 3 weeks to resolve sore throat and congestion but GI issues have worsened over the last 5 weeks. Alternate between diarrhea and constipation, gas, cramping, MCAS worse. Passed out earlier this week when experiencing cramping. Had strange derealization experience at that time, kind of like a flashback or deja vu. Fatigue and cognitive issues are getting worse as well.
Analysis
My tell-tale test for ME/CFS and Long COVID is massive over-representation of the 0-9%ile. The number in each percentile range should be around the same in a normal microbiome. These are often different from patient to patient. For other ME/CFS or Long COVID analysis, see this page.
Percentile
Genus
Species
0 – 9
51
72
10 – 19
12
18
20 – 29
18
18
30 – 39
14
18
40 – 49
16
20
50 – 59
19
20
60 – 69
13
19
70 – 79
26
18
80 – 89
17
18
90 – 99
17
22
Looking at Dr. Jason Hawrelak Recommendations, we see a lot of items out of position.
The Bacteria deemed Unhealthy list had some interesting items:
Rickettsia at 99%ile and Ehrlichia at 96%ile — this genus was the focus of Dr. Cecile Jadin work with ME/CFS over the last 3 decades. I recently did another post on these High Tick-borne Bacteria Counts (P.S. Dr. Jadin is working on a draft of her current protocol for this site — stay tune)
Faecalibacterium prausnitzii species at 17%ile, Reduced Ability to handle inflammation
As with another person who had ME/CFS and then Long COVID, let us look at the matches to published literature:
Other matches were interesting, Insomnia (0 %ile) 0 of 26, which implies that sleep issues are likely atypical. These are very rough estimates (the studies were done with different lab processes, so the data is fuzzy).
Going Forward
I started with the “Just give me Suggestions” and then manually did the 5 items above. Why? To give emphasis to the likely bacteria that may be of main concerns. So we see:
The highest (and lowest) priority were 466 and -453. So our emphasis would be items over 233 and below 227 to give us the best odds. Yes, odds — everything is done by fuzzy logic and probability.
Nicotine (not smoking, but a nicotine patch — I got an email from a user that had a major recovery using it)
rifaximin (antibiotic)s — which is often used by ME/CFS specialists [Src] and Rifaximin and CFS and often for Irritable Bowel Syndrome (297 citations on PubMed). My suggestion is to read up on how MDs diagnosis IBS and emphasis those symptoms. Then suggest this antibiotic (if the MD does not). My experience is that you want to craft your meeting with MD, so they will go where you want to go. Do not just do verbal diarrhea of symptoms, you will randomize (and perhaps frustrate) the MD. When you want the MD to go down a particular path, tune your story to their thinking.
Flipping over to Food Menu Planner we see a short list of high priority items. The top one: inulin and fiber cited above are a convergence… but what about the other oddities?
As a reminder, many studies use the above nutrients (and the food it comes from may not have been studied). The Food Menu attempt to resolve this disconnect. So Artichokes of different types should be regularly on your supper menu — perhaps with pea soup or just boiled peas.
Questions
My current diet (low carb, higher saturated fat, high red meat) is a poor choice according to these results. The low carb approach works well for my blood sugar and for keeping my weight down, but I do crave good carbs. I eat a lot of vegetables but it is impossible to get enough fiber that way. I had been supplementing with a rotation of psyllium, flax and chia. I will slowly adjust my diet to a higher carb, lower fat one and see how I respond. I have done well with oats in the past. I think as long as I combine the starches with lean protein I will do fine.
I used inulin during my first Covid infection and seemed to do well with it.
With regard to probiotics, bacillus subtilis looks to be a great choice, but different strains are used in the studies and most are not available commercially. The one commercially available microbiome labs /hu58 is marginally “likely safe”.
I am going to try Yakult. What would be your second choice?
Nicotine is interesting. This was talked about early on as being protected for Covid. Now it is gaining popularity as many are trying for Long Covid.
It is disappointing there are no strong consensus herbs or spices.
Feedback.
A: Concerning Probiotics, there is a second approach — looking at the genes you have in your bacteria and what they are not producing enough of.
The top 1 is Escherichia coli — available in two products: Mutaflor and Symbioflor-2. The next ones that are relatively easy to obtain are Bacillus subtilis and a specific species: Bacillus subtilis subsp. natto. This later item is available in many Japanese food sections of some grocery stores. It is just called Natto. It is made using soy which is also on your positive list. It also is a fibrinolytic (unthickens thick blood).
Q: “Should I consider rosemary stronger because of ursolic acid?”
A: No, the numbers indicated confidence of the item having a positive or negative effect. They are not “better” or “stronger” numbers, just more likely to have some effect (may be minor). We are using fuzzy logic, hence odds and the odds are on causing shifts and NOT the amount of shift. That is all that we can get from the studies usually. Bacillus subtilis subsp. natto
Bottom Line
This microbiome matches the pattern for ME/CFS and Long COVID. Most of the suggests have been studied with ME/CFS with positive results. Now it is just a matter of doing. After 6-10 weeks do another microbiome sample so you may make the next course adjustment. Most people cascade into ME/CFS, getting out is a dog-legged journey.
Addendum Exploration
I decided to look how the indices change with age. As you can see below, in general they decrease or increase significantly with age as I would expect. For more information see this earlier post.
.
Symptom Name
Shannon
Simpson
Chao
Shannon Rank
Simpson Rank
Chao Rank
Obs
Age: 0-10
1.576
0.118
8788
33.1
65.2
44.8
21
Age: 20-30
1.599
0.065
11592
32.2
49.7
52.6
57
Age: 30-40
1.579
0.06
11119
31.9
43.5
52.9
153
Age: 40-50
1.62
0.067
10433
34.8
47.1
50.5
106
Age: 50-60
1.605
0.045
11728
32.8
34.1
55.3
47
Age: 60-70
1.488
0.033
13580
28
26
60.7
22
Alpha Diversity Indices:
For a general introduction.. Personally, they are unlikely to be useful in an individual context and are complex to fully understand. I include this as an exploration
Closest to: DePaul University Fatigue Questionnaire : Does physical activity make you feel better; Age: 60-70; Comorbid: Restless Leg; Onset: less than 08 years since onset; DePaul University Fatigue Questionnaire : Chemical sensitivity
Recent Comments