Recap of this Journey

For new readers: I have had Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) three times in my life and recovered each time. As a result of work stress, I am currently in a ‘flare’, because it was sudden onset and I realized what it was on day one and took aggressive action it did not become established. Established usually means six months of tests ruling out all of the possible alternative causes for the symptoms!

The model foe ME/CFS that I use is a microbiome dysfunction. I reached this conclusion long before mainstream research started to investigate and confirm that it does appear to be that, Some recent literature:

• Does the microbiome and virome contribute to myalgic encephalomyelitis/chronic fatigue syndrome? [2018]
• Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome. [2017]
• A Pair of Identical Twins Discordant for Myalgic Encephalomyelitis/Chronic Fatigue SyndromeDiffer in Physiological Parameters and Gut Microbiome Composition. [2016]
• Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome. [2016]

Instead of the usual 6 months of testing for what is not there, I proceeded to get my ubiome done. I had two earlier ones done from when I was in remission. I have an actual base line to compare to. This makes interpreting data a lot simpler. It also mean that I could quickly confirm ‘my gut feeling’ that is was ME flaring.

My earlier posts on the progression are below

• Sudden Onset ME Flare – uBiome One Week Later
• uBiome progression in ME Flare
• ubiome followup

First, let us review my perceived changes

Following suggestions from my last microbiome results

I had an interesting experience with a morning bowel of barley (β-Glucan) with unpasteurized yogurt with beet sugar. The first two days, felt good, day 3 & 4 sore throat appeared. Missed a day and sore throat disappear. Back on barley and day 2, sore throat re-appear, more mild than before. Disappeared a couple of days later.

I am assuming that the barley and beet sugar feeds bacteria that are attacking other bacteria significantly. The wife was surprised when she tasted the beet sugar — it was not as sweet as cane sugar. I must admit to be confused by the sugar industry saying they are identical, and do find some support for them being different, like in this article.

Oats or barley for β-glucan

 This study compares in the same experiment the β-glucan content of nine barley and 10 oat genotypes grown at two locations in each of two years (i.e., four environments) in North Dakota. Averaged across genotypes, total β-glucan content of barley and oat groat was similar.

Comparisons of β-Glucan Content of Barley and Oat , 1999

Symptom Changes

• Night sweats have largely disappeared.
• Longer periods of mild physical activity before warning signs of two much activity (hiccups — a family trait that my kids always have when they are over tired. Sweats (even on a cold morning with no jacket), lisp in speech appears. By longer, I mean has increased from about 11 minutes until just under 20 minutes.
  • I can handle a 20 minute drive fine and keep to that distance bound. When I have gone longer, suddenly a ton of bricks hits, no gradual tiring.
• Longer periods of sleep at night and more sleep. In the past it was short periods only (90-120 minute) then I was awake for a while. Now, I may get up to 6 hrs in a stretch.
• Much more refreshed at waking in the morning.
• Weight loss — some 20 lbs. Little appetite.
• Still experiencing some Multiple Chemical Sensitivity issues, minor — but my work location is toxic with them, so it’s working remotely or leave as the only viable options.

UBiome Results

In my last post I gave the history of my readings for Lactobacillus, Bifidobacterium and Akkermansia. There was a little improvement in two of them,. but they are still magnitudes below my past normals.

Other Good News

Old News – Ubiome Edition

On the image below, the 2018 values are from remission, 2019 are during the flare.

In terms of the rare/elusive bacteria, we see many of them disappear as the flare progresses, and strangers appear. The strangers are disappearing and some old friends, like Caldicoprobacter are returning. The high Bacillus count was likely from taking Bacillus coagulans as a probiotic.

Old News – MicrobiomePrescription Edition

In terms of symptoms associated with bacteria, there was a significant drop in the number of Condition Matches. We must be careful not to read too much into that, because a microbiome in the process of changing (which we see above) will not match the patterns of people who are stable.

Bottom Line

The direction is improving. The improvement can be seen in both the microbiome and the symptoms moving closer to my pre-flare state. Recovery is fragile and in one sense, I am likely in the most dangerous time — significant symptom improvement and one could stop being diligent in keeping to a treatment plan. Over the decades, I have seen too many people make a good solid recovery and then crash because they pushed themselves too far in recovery.

My criteria is simple and objective: Microbiome must return to the older state, especially the levels of lactobacillus and bifidobacteria; but also for other genus that either waxed or waned during the flare. Being disciplined and objective is essential.

I am still “living in a plastic bubble” of restrictions. The bubble is slowly expanding.

I just got my ubiome results today. The sample was taken after one month on Seed Probiotics. I believe that the Seed Probiotics have made a significant positive impact on me, but the impact that I was most hoping for was seeing more lactobacillus AND bifidobacterium being reported.

See this update on the results after 2 months on Seed.

The answer is, it may.

For new readers, a ME/CFS flare was triggered by work stress around the 12 of March, 2019 — dramatic changes seen across my microbiome (separate posts on these). I am still recovering.

Sample readings

From the last sample (where I had stopped things that I should not have – sampled 04-30) until this time, we see a 10 fold increase in Lactobacillus, but not a single bifidobacterium has appeared. Akkermansia is often associated with these two, so I include it.

I will be continuing on with Seed Probiotic and plan to do my next sample in 8 days. I am feeling better and ME/CFS symptoms are reducing — whether that is a natural recovery or impacted by Seed, is a matter for speculation.

Bottom Line

The evidence for Seed persisting is weak. Good evidence would have been both Lactobacillus and Bifidobacterium to make significant improvement.

Personally, I am happy with it for the bacteriocins (natural antibiotics) appears to be in it. I discovered this the hard way. One night I forgot that I had taken 2 capsules an hour before and took a second dose. It was a rough night.

Some Comments from Facebook on this Post

We will see what next month’s numbers are like.

Some readers have asked me to explain my view of what causes a wide range of conditions – from diabetes to autism, from myalgic encephalomyelitis to parkinson’s.

At a high level, there are three dominant factors:

• DNA – every autoimmune condition has SNP variations associated. This does not mean you will get the condition — just have greater odds of getting it. (1151 articles on PubMed)
• Epigenetic changes to DNA. This means that some environment influence has caused DNA functions to be turn off or on (or scale).
  • Classic examples are stress (5556 articles on PubMed),
  • “The mothers have eaten unripe grapes and the children’s teeth are set on edge”: the potential inter-generational effects of the Holocaust on chronic morbidity in Holocaust survivors’ offspring. [2014]
• Microbiome – every condition has microbiome shifts associated with it with more being reported every year
  • 1134 articles on PubMed
  • Microbiota regulate the development and function of the immune cells. [2018]

And genetics to microbiome:

• The effect of host genetics on the gut microbiome. [2016]
• The effect of heritability and host genetics on the gut microbiota and metabolic syndrome. [2017]

And last, is consequences of infection and even immunization which can alter the microbiome — often in a long lasting way. The best study example occurred in Bergen Norway. 60% of CFS suffers developed the condition after a flu (or ‘flu-like’) illness.

Each factor interacts with the other factors and if you are unlucky, you have a struggle ahead of you. Of the above factors, the microbiome is the simplest to adjust.

Modifying epigenetic changes is more challenging – with stress being likely the only exception. Stress induced epigenetic changes may be reduced or reversed with full removal of stress (speculation) — which is not a trivial path. We may need almost 100% removal of stress, not just reducing it. We know that diet can invoke epigenetic changes – just do not know how. Science is still working on just detecting epigenetic, modification may be decades away.

This perspective is highlighted in this article:

The genetics of human longevity: an intricacy of genes, environment, culture and microbiome [2017].

At what microbiome level may we need to go down to?

Twins with identical DNA with one having a condition and another not, is the classic way of controlling for DNA variation.

” We collected fecal samples and clinical metadata from 20 monozygotic Korean twins … Finally, our unique study design allowed us to examine the strain similarity between twins, and we found that twins demonstrate strain-level differences in composition despite species-level similarities. “

Sub-clinical detection of gut microbial biomarkers of obesity and type 2 diabetes. 2016]

Bottom Line

The microbiome is the easiest factor to address. It is not an easy to do. Just the easiest of the available choices. It is made more comlex by different diets, life style (yes, exercising regularly alters the microbiome) and even age (diversity decreases with age).

Doing a few more hours of reviewing PubMed studies, I came across “Fecal metagenomic profiles in subgroups of patients with myalgic encephalomyelitis/chronic fatigue syndrome” [2017] There were some interesting findings.

Increased abundance of unclassified Alistipes and decreased Faecalibacterium emerged as the top biomarkers of ME/CFS with IBS; while increased unclassified Bacteroides abundance and decreased Bacteroides vulgatus were the top biomarkers of ME/CFS without IBS. Despite findings of differences in bacterial taxa and metabolic pathways defining ME/CFS subgroups, decreased metabolic pathways associated with unsaturated fatty acid biosynthesis and increased atrazine degradation pathways were independent of IBS co-morbidity. Increased vitamin B6 biosynthesis/salvage and pyrimidine ribonucleoside degradation were the top metabolic pathways in ME/CFS without IBS as well as in the total ME/CFS cohort. In ME/CFS subgroups, symptom severity measures including pain, fatigue, and reduced motivation were correlated with the abundance of distinct bacterial taxa and metabolic pathways.

The differences in ME/CFS without IBS were driven by the increased abundance of members of Pseudomonadales order, the Clostridiaceae and Pseudomonadaceae family, and the Clostridium, Pseudomonas, Pseudoflavonifractor, Eggerthella, and Coprobacillus genera and the decreased abundance of members of the Dorea genus. The 13 bacterial species driving the differences between the ME/CFS without IBS and control groups were D. formicigenerans, C. catus, and P. distasonis, (all decreased in ME/CFS without IBS) and unclassified Bacteroides, R. gnavus, D. longicatena, P. capillosus, E. lenta, C. symbiosum and scindens, C. bacterium, and Clostridium cf. (all increased in ME/CFS without IBS).

From the prior study (that did not separate with and without IBS), we have:

We observed reduced levels of members of the dominant phylum Firmicutes, also noted repeatedly in Crohn’s disease patients [13, 37, 38]. Proteobacteria were more abundant in ME/CFS patients than in controls, observed as well in inflammatory bowel disease (IBD) patients [39, 40]. 
significantly lower levels of the genus Faecalibacterium, a member of the Ruminococcaceae in the ME/CFS population. For example, Faecalibacterium prausnitzii, which produces an anti-inflammatory protein [45], is reduced in ME/CFS cases relative to controls. ….  found a decrease in Bifidobacterium, previously observed in IBS [53–57], IBD [58], and type II diabetes [59]. Bifidobacteria are a group of lactic acid-producing bacteria that are widely used as probiotics and as targets for prebiosis [60]. Treatment with Bifidobacterium infantis 35624 was reported to reduce CRP levels in a cohort of ME/CFS patients [61].

Reduced diversity and altered composition of the gut microbiome in individuals with myalgic encephalomyelitis/chronic fatigue syndrome [2016]

Bottom Line

This reinforced my hypothesis that symptoms (and perhaps official diagnosis) are strongly associated with microbiome dysfunction. It reinforces the 1998 study from Australia of microbiome dysfunction.

These reports will be incorporated into the condition profiles which need to be updated to the more sensitive Box-Plot code base.

A reader forwarded a patent application ( 16701. (WO2019025573) TREATMENT OR PREVENTION OF GASTROINTESTINAL DYSBIOSIS ) to me and asked me to look at it. Patents are always interesting read because they often refer to unpublished studies and may include speculation.

This patent described the use of Methylococcus capsulatus or a lysate of Methylococcus capsulatus and “provides a method for the treatment or prevention of a disease or condition selected from small intestine bacterial overgrowth (SIBO), small intestine fungal overgrowth syndrome (SIFO), Gl tract cancers, breast cancer, neurological disorders, malnutrition, chronic fatigue syndrome, autism, cardiovascular diseases and Gl tract infections in a subject with Gl tract dysbiosis “.

Medical patents are interesting because while you can get them in a few countries, if there is no equipment involved with it somehow — the patent will not be enforced (see this post). For example, you can patent how you kill (lysate) this bacteria, but you can’t patent the use of it in a capsule.

What do we know about Methylococcus capsulatus

Wikipedia provides an image and it’s hierarchy. It is usually used industrially to produce animal feed.

Kingdom:	Bacteria
Phylum:	Proteobacteria
Class:	Gammaproteobacteria
Order:	Methylococcales
Family:	Methylococcaceae
Genus:	Methylococcus
Species:	M. capsulatus

What PubMed says

A good start is this comparison to something like Mutaflor (E.Coli Nissle 1917) and Culturelle.

we showed that a bacterial meal of a non-commensal, non-pathogenic methanotrophic soil bacterium, Methylococcus capsulatus Bath prevents experimentally induced colitis in a murine model of IBD.  ….  we show that M. capsulatus, a soil bacterium adheres specifically to human dendritic cells, influencing DC maturation, cytokine production, and subsequent T cell activation, proliferation and differentiation. We characterize the immune modulatory properties of M. capsulatus and compare its immunological properties to those of another Gram-negative gammaproteobacterium, the commensal Escherichia coli K12, and the immune modulatory Gram-positive probiotic bacterium, Lactobacillus rhamnosus GG in vitro. M. capsulatus induces intermediate phenotypic and functional DC maturation. In a mixed lymphocyte reaction M. capsulatus-primed monocyte-derived dendritic cells (MoDCs) enhance T cell expression of CD25, the γ-chain of the high affinity IL-2 receptor, supports cell proliferation, and induce a T cell cytokine profile different from both E. coli K12 and Lactobacillus rhamnosus GG. M. capsulatus Bath thus interacts specifically with MoDC, affecting MoDC maturation, cytokine profile, and subsequent MoDC directed T cell polarization.

The Soil Bacterium Methylococcus capsulatus Bath Interacts with Human Dendritic Cells to Modulate Immune Function. [2017]

 M. capsulatus Bath induced the highest levels of IL-6, IL-10 and IL-12 secretion from dendritic cells, suggesting that this strain generally the post potent inducer of cytokine secretion. These results show that M. capsulatus Bath exhibit immunogenic properties in mammalian in vitro systems which diverge from that of E. coli Nissle 1917. This may provide clues to how M. capsulatus Bath influence the adaptive immune system in vivo. However, further in vivo experiments are required for a complete understanding of how this strain ameliorates intestinal inflammation in animal models.

Effects of the non-commensal Methylococcus capsulatus Bath on mammalian immune cells. [2015]

• ” significant production of hydrogen peroxide is observed” [2019]
• “Our results show that a bacterial meal of the noncommensal bacterium M. capsulatus (Bath) has the potential to attenuate DSS-induced colitis in mice by enhancing colonic barrier function, as judged by increased epithelial proliferation and increased Muc2 transcription. [2013]
• ”  Previous studies show that bacterial meal (BM) containing mainly Methylococcus capsulatus grown on natural gas is a suitable protein source for salmonids. The BM is rich in nucleotides, phospholipids, and small peptides that might be beneficial for intestinal homeostasis…. can be used to prevent SBM-induced enteritis in Atlantic salmon. ” [2011]

Bottom Line

It’s interesting that it appears that it is available today as fish meal.

Methylococcus capsulatus is a methanotroph, a bacterium that metabolises methane. Salmon will consume pelletised protein made from these bacteria. And that could be handy for fish farmers.
Calysta, a biotechnology firm in Menlo Park, California, proposes to take advantage of the rock-bottom price of methane, a consequence of the spread of natural-gas fracking, to breed Methylococci en masse as a substitute for the fish-meal such farmers now feed to their charges.
The EU and Norway have already approved the use of Methylococcus-based fish food. Though America has yet to follow suit, this means there is a large available market for the stuff.

Natural Gas Fracked bacterial fishmeal can save the worlds fish and enable a lot more farmed fish [2015]

This creates an interesting roadblock for getting it to the human market — it is uber-cheap, easy to produce, and not patentable. FeedKind™ Protein is the trade name, manufactured by http://calysta.com/