Recent Updates

lassesen 4:29 pm on June 12, 2019  

Quick start to 2 blogs and an analysis site

My primary concern for the last 20 years was been the condition known as Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). I deduced some seven+ years ago that the simplest explanation of the multitude of symptoms and abnormalities reported was a stable microbiome dysfunction. This explanation can also be applied to many other conditions. My focus is still on ME/CFS but I wish to make the data and algorithms available to people with any conditions. My old home page is here (dry technical).

The basic model that is supported by studies is:

  • DNA Snps that results in increased risk
  • Environmental changes of DNA (epigenetics) that further increase risk
  • Microbiome function that acts as a catalyst to the risk.

The microbiome is the simplest to alter technically — but very complex to alter because there are thousands of bacteria that interact with each other in the human body. DNA can also encourage some bacteria and discourage others. Example: Typhoid Mary is an excellent example of some one whose DNA and a nasty bacterial infection co-existed nicely.

Does changing the microbiome work for ME/CFS?

Answer is yes:

Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndrome: neuropsychological symptoms and sex comparisons , 2018
Ep. 49 Interview Ken Lassesen: Using AI to Improve the Gut Microbiome

Recommended Site For Testing

With ME/CFS, there is always a nasty cost factor for testing. My usual recommendation is for the cheapest, high quality provider that provides information for upload to my analysis site. Some sites provide a mountain more of information — but the benefit from that extra information is almost nothing (and it adds $$$$ and complexity).

  • uBiome.com is shutting down. This had been my personal usual site because using a variety of techniques, the cost was $25/sample. Don’t order from there.
  • BiomeSight.com (EU based but serves the world) – discount code “MICRO” has integrated with my analysis site with automatic data transfer. For most people it is likely the best deal.
  • Thryve (US Based) is what I have used. Their reports may be processed here for independent suggestions. I would also recommend

Who am I?

I am a citizen-scientist with reasonable scientist credentials: taught Chemistry and Physics at College Level; Master of Science, accepted for the PhD program, certified data scientist with R, one of the top mathematics and physics competition students in Canada during my university years, etc.

I am a closet academic — so I give links to my source of information everywhere and usually keep them to the highest quality sources (PubMed, professional journals). I have even had a letter of mine published in the Lancet.

The Sites

  • This site — over 1200 blog posts published over the last 5 years. This is where I publish most. You can subscribe to get new posts by email.
  • Microbiome Prescription site – started in 2018. This is a massive data store with a variety of artificial intelligence algorithms applied to it. Almost 800 people have uploaded their microbiome results to it and many annotated it with their symptoms.
  • Microbiome Prescription Word Press – started recently. This is intended as a reference to the above site. Just essential pages and a bunch of homemade videos taking you through some features.
  • Facebook Site: Where I usually post new blog entries and the occasional odd note that is not worth a blog post. Make sure that you like it so you get notices of new posts.

Findings to Date

The assumption that bacteria shifts connect to symptoms appears confirmed using the upload microbiomes.

  • We have found statistically significant patterns of some bacteria to symptoms, see this post
  • We appear to have a high probability of correctly predicting symptoms from a microbiome report. See this post.

These findings can be independently confirmed by using the public shared data at: http://lassesen.com/ubiome/

Tools to Help

The Microbiome Prescription site is a theoretical site, that is, it works from the logical application of data and is not based on actual human experience. It does have the ability to create suggestions of things to take and to avoid to try reducing abnormalities in your microbiome. It supports multiple models and algorithms because we do not know which actually works best.

The site states that the suggestions should be reviewed by a medical professional. The source of the information is provided by links (hundreds of articles are cited).

Evolving Story

As more data comes in, and more insight happens, there will be more posts and more features (some labelled experimental — because I am unsure of their accuracy) will be added. This is citizen science.

Video to kickstart using your microbiome use

lassesen 1:22 pm on October 8, 2017  

Overview of this Blog and the Microbiome

My ideas on this blog have evolved, as more and more information becomes available. This post is an attempt to bring readers up to date with my current thinking. I am striving to be transparent in my logic — showing the evidence I am working from, and my thought processes.

Notes to Treating Physicians     Quick Self Start on treating CFS

Analysis of Microbiome/stool with recommendations

Site: has moved to http://microbiomeprescription.azurewebsites.net

The data is available in an online collaborative python workbook for analysis. See this post.

Microbiome Definition of CFS/FM/IBS

A coarse condition that results from:

  • Low or no Lactobacillus, AND/OR
  • Low or no Bifidobacteria , AND/OR
  • Low or no E.Coli , AND/OR
  • A marked increase in number of bacteria genus (as measured by uBiome) to the top range
    • Most of these genus are hostile to/suppress Lactobacillus, Bifidobacteria, E.Coli
    • Several are two or more times higher than normally seen
    • The number of bacteria genus goes very high (using uBiome results), but most of them are low amounts.
      (“Death by a thousand microbiome cuts” and not “Death by a single bacteria blow”)
  • The appearance of rarely seen bacteria genus in uBiome Samples.

A finer definition would be a condition with a significant number of abnormalities in the ‘Autoimmune profiles see this page for the current criteria (i.e. over 25%).

The specific genus and their interactions determine the symptoms seen — likely due to the over- or under-production of metabolites (chemicals). Other autoimmune conditions may share these core shifts. The specific high and low bacteria determine the symptoms if the person was the DNA/SNP associated with the symptoms.

Replace the metabolites produced by the missing bacteria

Replacing the metabolites should result in the reduction of symptoms associated with a deficiency of these metabolites.

See this post for the study references. These items should/could be done continuously.

Other Supplements Reported to Help

Bootstrapping Bifidobacterium and Lactobacillus

The items below were found in studies to increase bifidobacterium and lactobacillus:

Unless the bifidobacterium and lactobacillus (B&L) are human sourced, there is almost zero chance of taking up residency. Taking probiotics will not allow B&L to get established. In fact, there are grounds to believe that most commercial probiotics actually reduce your  native B&L. You want to encourage your native B&L. See this post for citations.

Bootstrapping E.Coli

The E.Coli probiotics below are human sourced and known to take up residency in the human gut.

  • Core: D-Ribose a preferred food that it uses
  • Mutaflor probiotics — E.Coli Nissle 1917
  • Symbioflor 2 — multiple strains

Dealing with the other microbiome shifts

The other microbiome shifts appear to be in different clusters of microbiome shifts. This 2017 paper by Peterson, Klimas, Komaroff, Lipkin (and a stack of other CFS researchers) makes that clear in its title: “Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome”.

The best way at present to proceed is to order an analysis from uBiome. (Disclosure: I have no financial interest in this company.) When your get your results back, log in, click on the “Compare” tab, then go to “Genus,” and click on “ratio” twice, so the results are in descending order.

This is the “hit list” of what you are trying to reduce. DataPunk provides a nice summary of what we know about these. See, for example, Alistipes:

At this point, we run into a logistical challenge.  You want to avoid items that are “Enhanced By” (which is in common across all of the high items) and take the items that are “Inhibited By” (which are not on any of the “Enhanced By” lists).  You may also wish to reduce foods that are high in items listed in “Nutrients/Substrates.”  It becomes a jig-saw puzzle! I have done this exercise for many readers’ uBiome results:

I have discovered that DataPunk is not absolutely current, and have started creating posts based on its data, and then added studies from 2016 and 2017 to the page. Past pages are below, for current list MicrobiomePrescription site.

nihms-731256-f0001

Src: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4754147/

General Suggestions (no uBiome results)

Some of these items are contraindicated with a few uBiomes that I have reviewed. This likely is why person B reports no results while person A reports improvement. Example: Magnesium is usually very helpful — but there are a few cases where it encourages overgrowth of undesired  bacteria.

Probiotics

Most probiotics do not take up residency. They are “here today, gone tomorrow”. Their primary role in my model is producing natural antibiotics against other bacteria. For example:

Probiotics should be rotated: 2 weeks on a specific one, then several weeks off. As a general rule, you want about  6-12 B CFU taken three times a day (or 2-3 times the recommended dosage) — but work up slowly because you may get be a major herx! In general, do not take Lactobacillus with Bifidobacteria or with E.Coli etc. Keep to one family per cycle. You do not want them to kill off one another!

Why 3x per day? Because almost none of them are detected after 12-24 hrs. So to keep them — and the production of natural antibiotics — going, you need to keep taking them during the day. See this post for citations.

The following probiotics commonly seem to help people with CFS/Lyme/Fibro:

Some probiotics, however, may make your symptoms worse! And, unfortunately, most commercial probiotics contains some of these. At the moment Bifidobacterium animalis, Saccharomyces boulardii and Lactobacillus acidophilus are on my best to totally avoid list.

  • “. The findings show that the six species of Bifidobacterium differed in their ability to relieve constipation. B. longum, B. infantis and B. bifidum were the most effective in relieving constipation, B. adolescentis and B. breve were partially effective and B. animalis was not effective. Furthermore, edible Bifidobacterium treated constipation by increasing the abundance of Lactobacillus and decreasing the abundance of Alistipes, Odoribacter and Clostridium. .” [2017]

On my neutral list (no clear benefit) is Lactobacillus Plantarum.

Teas

Some teas can also be antibiotics (among other roles). There are two teas that seem to produce significant results quickly:

Again, rotate and, if practical, change brands too. Their antibiotic compounds are different from different sources.

Herbs and Spices

The best choice needs examination of your microbiome (i.e. uBiome results) and doing the work cited above.  Survey results found:

  1. Neem and Oregano with 80% improving
  2. Olive Leaf and Licorice with 56% improving
  3. Thyme with 50% improving
  4. Wormwood and Tulsi with 33% improving

Other things

If you do not know your microbiome, then see https://cfsremission.com/reader-surveys-of-probiotics-herbs-etc/  for suggestions. Your results will vary because your microbiome vary.

Thick blood is an issue also — but here things gets more complicated and not suitable for this recap.

Antibiotics can have a role — but getting prescriptions for the right ones can be a major challenge.

Metabolism Shifts

From volunteered data, we can identify some distinctive shifts, see Metabolism Explorer Summary

Bottom Line

Working with the microbiome and autoimmune is like working with fragments of the dead sea scrolls. For many bacteria we can identify it — what inhibits or encourages it is not known to modern medical science.  We have extremely thin slices of knowledge –Almonds enhances Bifidobacterium, Lactobacillus (B&L)  as do sesame seeds. What about sunflower seeds? Peanuts? Cashews? We find that Walnuts help the bacteria that inhibits B&L — so we cannot safely generalize to “all seeds/nuts are helpful”.

In many cases, we find that healthy diet or supplements demonstrated to work for normal people have the opposite effect on CFS and other altered microbiome conditions. This is made even worst because most of the studies were done on males and most people with CFS are females. We end up having to swim up-stream thru good and valid suggestions — that are just wrong for us.

My model is simple to understand and allows us to filter many suggestions and candidates. With the availability of uBiome testing (without needing a prescription!) we have entered the age of explicit treatment based on your unique microbiome. We do not know the role of many bacteria involved. We do not know what will inhibit or enhanced all of these bacteria. Frustrating little knowledge!

On the flip side, many readers have reported significant improvement, reduction of prescription medication, etc. so the model and suggestions have potential and thus hope of remission! Microbiome studies are exploding on PubMed, a lot of research is being done and we can often borrow their results.

This is an education post to facilitate discussing this approach with your medical professionals. It is not medical advice for the treatment of any medical condition. Always consult with your medical professional before doing any  changes of diet, supplements or activity. Some items cites may interfere with prescription medicines.

lassesen 6:31 am on April 30, 2021  

CFS/ME Research and the microbiome

A reader forwarded a new study from March, 2021. Unfortunately, ME/CFS seems to be in an infinite loop of similar hypotheses that keep repeating with a preliminary investigation and recommendations that are not followed up. I have seen this pattern over the decades that I have followed CFS/ME research.

Potential role of microbiome in Chronic Fatigue Syndrome/Myalgic Encephalomyelits (CFS/ME)

The present research explored the composition of the intestinal and oral microbiota in CFS/ME patients as compared to healthy controls. The fecal metabolomic profile of a subgroup of CFS/ME patients was also compared with the one of healthy controls. The fecal and salivary bacterial composition in CFS/ME patients was investigated by Illumina sequencing of 16S rRNA gene amplicons. The metabolomic analysis was performed by an UHPLC-MS. The fecal microbiota of CFS/ME patients showed a reduction of Lachnospiraceae, particularly Anaerostipes, and an increased abundance of genera Bacteroides and Phascolarctobacterium compared to the non-CFS/ME groups. The oral microbiota of CFS/ME patients showed an increase of Rothia dentocariosa. The fecal metabolomic profile of CFS/ME patients revealed high levels of glutamic acid and argininosuccinic acid, together with a decrease of alpha-tocopherol. Our results reveal microbial signatures of dysbiosis in the intestinal microbiota of CFS/ME patients. Further studies are needed to better understand if the microbial composition changes are cause or consequence of the onset of CFS/ME and if they are related to any of the several secondary symptoms.

Abstract

This is not a new finding. Similar have been reported — dating back to 1998. For prior studies see these links:

Going thru the article and the methodology, I was disappointed on the use of ancient data-analysis (Principal Component Analysis, Canonical correspondence analysis) instead of Random Forest. Moving over to the good news.

The Microbiome of the ME/CFS mouth is a factor!

The study illustrated a clear pattern between controls, patients and the patients’ relatives


This suggests that there is a pre-disposition via the salivary microbiome for ME/CFS. The salivary microbiome is formed by kisses, and just being in the same living space (this was demonstrated in a recent study where the microbiome of family pets were transferred to the children [2021] [2021])

It is nice to see this clearly demonstrated. This has been reported prior Chronic fatigue syndrome patients have alterations in their oral microbiome composition and function. [Sep 2018]

In prior posts, over the last 7 years, I have flagged this issue:

What are the changes in the mouth bacteria (with links to what modifies these bacteria)

Bottom Line

The authors asked “if they are related to any of the several secondary symptoms“, the answer is yes. For several years we have demonstrated that on Microbiome Prescription with citizen science.

https://microbiomeprescription.com/Library/CitizenScience?pvalue=0.01&symptomIds=289

Similarly, “if the microbial composition changes are cause or consequence of the onset of CFS/ME” can be answered as: Some transitory event (i.e. infection, stress, vaccination) causes a change of the microbiome composition. This altered composition takes on a life of its own and cascade into ME/CFS.

My own experience, and some others, are that by altering the microbiome composition back towards normal, ME/CFS improves or disappears.

The unfortunate aspect is that it cannot be handled in ‘one drug solves it’ or a pro-forma cookbook by medical professionals. Every individual has a different microbiome shift with items suggested for one ME/CFS person being contraindicated for a different ME/CFS person based on their 16s determined microbiome and using the artificial intelligence used for suggestions on Microbiome Prescription.

My expectations are that they will be no traction towards treating ME/CFS by conventional researchers. The reason is simple — the ground rules for studies and processes will send them into cascading challenges which required “stepping outside” of establish processes to get traction. This has been described as the “Dogma of Conformity”.

lassesen 11:28 am on April 25, 2021  

A review of a new CFS/ME Hypothesis

A reader asked for my thoughts on “Pathophysiology of skeletal muscle disturbances in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)” 21 Apr 2021. With over 20 years of reading many many hypothesis of ME/CFS, I have learnt to look for earlier indicators that it will be unlikely.

First, “skeletal muscle disturbances” applies to a subset of ME/CFS only. The second item is simple – is this a new hypothesis or an old one-recycled? What I found was:

What is the new hypothesis?

The author’s earlier title was “A Unifying Hypothesis of the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): Recognitions from the finding of autoantibodies against ß2-adrenergic receptors” [2020] There is no reference to acylcarnitine in the document – this is a red flag for an under-researched paper. You want to cite and discuss prior papers on the same topic.

“sympathetic overactivity in the presence of vascular dysregulation by ß2AdR dysfunction causes predominance of vasoconstrictor influences in brain and skeletal muscles,”

The conclusion is below and amounts (IMHO) to a bunch of hand-waving. The key factor is that the hypothesis is really not testable (hence authors get credit for a publication, suffers of ME/CFS gets nothing).

Considering all the potential predisposing factors we think that in the presence of a high sympathetic tone dysfunction of the ß2AdR could play an essential role (conditio sine qua non) in the etiology of ME/CFS although secondary and rather complex mechanisms have to get involved and to interact, particularly in the chronification of the disease (Figs. 4 and 5). Dysfunction of the ß2AdR by autoantibodies, mutations and desensitization by chronic stress would favor vascular dysfunction and cause insufficient stimulation of the Na+/K+-ATPase at least as a risk factor together with other precipitating factors. There may be numbers of different, still unknown predispositions.

According to our hypothesis dysfunctions of the ß2AdR or post-receptor mechanisms, of the NHE1, the Na+/K+ATPase, the NCX, the RAAS and the KKS could be causally involved in ME/CFS and should therefore be further investigated. This concept offers potential novel strategies for the treatment of this debilitating disease.

The only use of the word “treatment” is in the last sentence.

Going to the earlier study by the same author, I read “Metabolic changes in ME/CFS are also in line with a concept of hypoxia and ischemia.” — that echoes the old hypercoagulation hypothesis from Dave Berg [1999, 2000]. The key difference is that Berg’s hypothesis was testable (via the ISAC Panel) and a variety of treatments (depending on the results). For myself, it worked and I went into full remission. This was confirmed in a trial but then a series of poorly done studies faded away. I recall one study that tested using baby-aspirin on ME/CFS patients and reported no results, thus dismissing the coagulation hypothesis.

A major factor in Berg’s hypothesis fading was the complexity of multiple treatment plans was more than most ME/CFS physicians wanted to deal with (give me one magic bullet please!) , patients referred to hematologists were tossed back because low grade chronic coagulation was not of interest to them.

How well studied is ß2-adrenergic receptors?

I checked PubMed and found there is only 16 results. Several deal with asthma, and thus I would expect an association to asthma to be in the ME/CFS literature – which I was unable to find

Bottom Line

I would drop this concept into the circular filing cabinet. It lacks any direct test results on ME/CFS patients to support it, offers no treatments. It is full of speculation and “reasoning”, i.e. “Therefore, QTc shortening can be explained only by ß2AdR dysfunction in the presence of intact ß1-adrenergic receptors and a high sympathetic tone.” The use of the phrase “can be explained only” instead of ” could be explained” signals spin-doctoring and salesmanship to me, not careful science.

‘

lassesen 6:56 am on April 20, 2021  

Piracetam for ME/CFS, Long Haul COVID brain fog

This morning I dropped a note to my physician about immune system activation symptoms from getting my 2nd covid shot. One item cited was suspected activation of coagulation resulting in brain fog. I mention that it disappears for half of the day with 300 mg of Piracetam. I expect an email back asking what is Piracetam?

From Wikipedia, you can get general background. It is NOT to be confused with paracetamol (acetaminophen). It’s sits in a murky space in the US, so while legal, without prescription, it can be hard to find.

It improves brain function for many conditions

  • [2020] After treatment, the quality of life scores was significantly higher than the control group, and the difference was statistically significant (P<0.05). For patients with vascular dementia after cerebral infarction, piracetam combined with nimodipine can improve the cognitive function, improve the quality of life, and have a significant clinical effect.
  • [2021] Although Piracetam is officially recognized as a nootropic, its enhancing effects in the healthy individual’s brain are moderate [104,54]. The racetam molecules are being used across a range of brain disorders, including Alzheimer’s disease, narcolepsy, ADHD, Parkinson’s disease and brain aging [105,106].
  • [2020] Piracetam shifted the balance of mitochondrial fission or fusion toward fusion, which is more favorable for ATP production, which would indirectly benefit synaptic function because of the energy requirements of synapses. 43 A review indicated favorable effects on neurotransmission and neuroplasticity. 44 Another report showed that the increased neurite length after piracetam treatment was accompanied by increased expression of the synaptic marker GAP43, thus improving neural plasticity. 45

In days long ago when I often fly between Seattle and India for work, I used a heparin-piracetam cocktail to reduce risk of DVT. As a side effect, I never experienced jet-lag.

  • [1998] ” The heparin-piracetam complex had a more pronounced anticoagulant and fibrinolytic activities than the individual components.”
  • [1993] “The particular efficacy of 8 g piracetam daily in 3 divided doses at 8-hourly intervals can be attributed to its unique dual mode of action; inhibition of platelet function by inhibition of thromboxane A2 synthetase or antagonism of thromboxane A2 and increased formation of prostaglandin I2, together with a rheological effect involving reduction in blood and plasma viscosity through an increase in cell membrane deformability and a reduction of 30-40% in the plasma concentrations of fibrinogen and von Willebrand’s factor”

This last study is why it is my go to when brain fog occurs. I have a mutation that results in higher levels of fibrinogen.

Coagulation in various forms in ME/CFS was demonstrated in the late 1990’s by David Berg. [Other Berg Links: [A,B, *] .

COVID Coagulation

Doing a search on PubMed for “covid coagulopathy“, we find over 1100 citations. For long haul covid to include persistent coagulation is very probable. It may be due to microbiome alterations or other mechanisms.

Bottom Line

Trying piracetam for brain fog is something to discuss with your MD. You may need to educate him about the contents of this article. The [1993] study was on humans and thus showed safety and also dosage (8 grams/day in 3 dosages).

lassesen 10:20 am on April 16, 2021  

Looking beyond bacteria

An Exploration of the microbiome economy using Microbiome Prescription and a 16s report.

Small intestinal bacterial overgrowth (SIBO)

This is detected by end products produced: Hydrogen and Methane and not specific bacteria.

We can explore for associations of different products of bacteria to symptoms

The challenge – Looking at almost 10,000 items for patterns. This is automated, so let us jump to results.

Predicted Symptoms

Support for multiple samples

Summary

The purpose is to discover associations. Association does not prove causality; but association often reflect severity of symptoms. This gives leads to explore…. Not canned answers…