In this post, I am going to represent my model as a series of diagram with the typical reported path “CFS after a flu-like illness” — which may actually be the flu!

• Metagenomics: A New Way to Illustrate the Crosstalk between Infectious Diseases and Host Microbiome [2015]. ” In particular, Firmicutes andProteobacteria phylum, as well as the Moraxellaceae family could be identified as the predominated bacteria in the patients with H1N1 influenza in both reports. It suggested the potential correlation between these bacteria and influenza infection.”
  
• Regulation of lung immunity and host defense by the intestinal microbiota. [2015]

The Stuck Microbiome

The microbiome normally returns to it’s prior state, this post looks at the evidence that a percentage does not return – and is often called post-infection fatigue (because the infection triggering it was known and was successfully treated).

The evidence from changing the microbiome (via a fecal transplant) results in remission strongly suggests that the microbiome is the source of the CFS symptoms.

The number of lines increases greatly as you move from the left to the right, and I have omitted many on the right side.

Items like stress and environmental chemicals, also alters the microbiome. There are DNA differences between people with CFS, FM and IBS. The set of symptoms that manifest appears to be a combination of microbiome shift and DNA of the person.

The research challenge is picking the item that is the origin, the one that arrows lead from. To me, the repeated remission reported by fecal transplants within days(although not all stay in remission) leads me to believe this is the root cause and the target for creating a true remission. Every study try to address the other areas have resulted in eventual symptom improvement but not remission.  For an approach to deem superior, it must:

• result in full remission within 3 days.
• persist for several months at least.

None of the many many protocols, except fecal transplants have reached this level.  Fecal transplants is not available to everyone — and unfortunately do not persist always.

My Thinking Evolution

One of the key understanding that I came to was that the trigger of CFS was not the maintainer of CFS. Think of smoking and lung cancer. If you get lung cancer and stop smoking, the lung cancer does not go away. The same applies to viruses that cause cancer — eliminating the virus does not eliminate the cancer. My focus went from looking for this mystical infection that have eluded researchers for decades to how this condition kept going.

The second stage was seeing that there are sets of “Post-Infection Syndromes”, especially one in Norway where the infection that caused it was known in a population and treatment was successful — but the symptoms kept going and going (with the percentage every few months going down). After two years, a percentage became stuck in the symptoms. Symptoms that would be CFS if the MD did not know about the triggering infection (but because it was known, it was not technically CFS by formal definition!). 

The third item was that fecal transplant result in immediate (for several months at least) remission for a high percentage of CFS patients. Yes, the transplant will impact the immune system — because the bacteria that the immune system is exposed to have been changed. When I looked at Jadin’s antibiotics and the gut bacteria analysis from Australia, we see that her antibiotics reduce the overgrowths (she believed she was treating occult ricketessia infection — but the same prescription also reduced the overgrowth).

The last item was that studies found that several diseases can be identified solely from a microbiome sample with 90% accuracy. There appears to be two relationshipd:

• a disease –> microbiome change AND
• a microbiome change –> SUPPORTS the disease.

Chicken and the egg — so I concluded that we need to break the egg.

Breaking the Eggs

You can break eggs by dropping them on the floor, using a sledge hammer, squeezing them in your hand until they break. We need to break the egg appropriately.

There is complexity because there are (at least) three families of bacteria with overgrowth and three with undergrowth and a drop of diversity. For all three of the undergrowth there are probiotics available (somewhere in the world).  But just taking them blindly does not result in a nice omelette.

Lactobacillus bacteria/probiotics (in general) reduces/kill Bifidobacterium and E.Coli (also undergrowth). Bifidobacterium probiotics increases lactobacillus.

My recommended recipe for our broken eggs is:

• Bifidobacterium probiotics containing many different bifidobacterium species and NO Lactobacillus. 5+ Billion CFU/day
  • See Commercial Bifidobacteria Probiotics post
  • and Bifidbacteria probiotics — best bang for the buck post
• E.Coli Probiotics (both are made in Germany):
  • Symbioflor-2 (6 species)  – appears best because one of the species appear to take up residency – can buy on Amazon.de ( 30 drops/ day for 43 days was used in a study to reduce IBS symptoms)
  • Mutaflor (1 Species, E.Coli Nissle 1917)
• Increase Variety of species (these do not contain any E.Coli, Lactobacillus or bifidobacterium)
  • Prescript Assist
  • General Biotic’s Equilibrium

My logic should be apparent. The overgrowth is more complicated because of antibiotic resistance. See Antibiotic Analysis and Herb Analysis.

Whether a positive only approach (probiotics) or a rotating (ant-bacteria + probiotics (which are also bacteria) is best varies between people.

I have just finished reading “Viruses, A very Short Introduction” by D.H. Crawford, Oxford University Press, 2011. It has been 30 years since I taught biology classes in high school and thought it would be good to get current.

Many virus are associated with CFS, and there have been no success in finding any specific one responsible. I found this table very interesting because it lists many of the virus associated with CFS — actually, to be clearer. Most of these viruses are in a latent state in the normal population and CFS patients have a far greater percentage in an active state.

So the question is: does the virus cause CFS or is the virus activation a result of the CFS, that is a side effect.

The author writes “The trigger for .. activation in an individual carrier are often quite clear and recognizable: decrease immunity due to drugs or illness, fever, increased levels of ultraviolet light (classically precipitated by a skiing trip), or menstruation and stress, but the molecular mechanisms involved are not understood.”

Probiotics and Viruses

We find that some bacteria (probiotics) inhibits viruses. If there are not there, then virus reactivation becomes more likely. A microbiome shift may result in latent viruses becoming active.

“Based on experimental studies, probiotics may exert antiviral effects directly in probiotic-virus interaction or via stimulation of the immune system.” [2014]

” probiotics decreased the presence of picornaviruses after 3 months, which may imply that probiotics play a role against viruses causing common cold.” [2014]

• Antiviral activity of Bifidobacterium adolescentis SPM 0214 against herpes simplex virus type 1.[2012]
• In vitro study of the effect of a probiotic bacterium Lactobacillus rhamnosus against herpes simplex virus type 1.[2012]
• [Inhibition of herpes simplex virus type 1 reproduction by probiotic bacteria in vitro]. [2010]
• [Effect of probiotic lactic acid bacteria strains on virus infection]. [2007]

I expanded my post on low dose naltrexone  and SED came up — I thought that it is time to look at SED and the microbiome — is there a relationship?

According to Dave Berg, Hemex (hypercoagulation theory):
“The ESR (erythrocyte sedimentation rate – red blood cell sed rate) is called SED RATE for short. We are close to having enough data to publish that the normal range for SED RATES should start above 3 or 4. Values below this are correlated with high SFM values. As the Soluble Fibrin Monomer (SFM) goes up in the plasma, these molecules form dimers (2 stuck together). This physically blocks the RBCs from settling out of the plasma, thus a low sed rate.” [Townhall]

That is, if your SED rate is 0,1,2 you have a high probability of having excessive soluble fibrin monomer. This results in one (of several types) of  hypercoagulation (thick blood). It can be treated. SED rates are common taken (with MDs focused on high SED rates instead of low — just like they are focused on high temperature and not low temperatures)

So, to PubMed, as usual.

• “Clumping reaction, using standard suspension of Staphylococcal aureus Newman D-2-C strain and various substrates, was quantitatively tested. It has been shown that clumping occurs in fibrin lysate containing soluble fibrin monomer complexes unclottable by thrombin.” [1967]
• ” One hundred eleven strains of S. haemolyticus, 10 strains of viridans group Streptococcus, … were clumped by human plasma.” [1979]
• ” Purified fibronectin was capable of clumping Staphylococcus aureus strains in concentrations identical with concentrations of fibronectin in human plasma” [1981]

It is interesting that Staphylococcus aureus which I covered in an earlier post showed up so often (there could be others bacteria also). A vaccine against this resulted in significant remission of CFS.

“Staphylococcus aureus is notorious for its ability to become resistant to antibiotics. Infections caused by antibiotic-resistant strains often occur in epidemic waves initiated by one or a few successful clones.” [2010]

“Staphylococcus aureus can exemplify better than any other human pathogen the adaptive evolution of bacteria in the antibiotic era, as it has demonstrated a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin and methicillin, until the most recent, linezolid and daptomycin. Resistance mechanisms include enzymatic inactivation of the antibiotic (penicillinase and aminoglycoside-modification enzymes), alteration of the target with decreased affinity for the antibiotic (notable examples being penicillin-binding protein 2a of methicillin-resistant S. aureus and D-Ala-D-Lac of peptidoglycan precursors of vancomycin-resistant strains), trapping of the antibiotic (for vancomycin and possibly daptomycin) and efflux pumps (fluoroquinolones and tetracycline). Complex genetic arrays (staphylococcal chromosomal cassette mec elements or thevanA operon) have been acquired by S. aureus through horizontal gene transfer, while resistance to other antibiotics, including some of the most recent ones (e.g., fluoroquinolones, linezolid and daptomycin) have developed through spontaneous mutations and positive selection. Detection of the resistance mechanisms and their genetic basis is an important support to antibiotic susceptibility surveillance in S. aureus.” [2007]

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The joy (and bane) of having a model is that when new information arrives, you can see if it supports or disagrees with the model. In some cases, it become a neutral — not sufficient information to make a determination.

The National ME/FM Action Network did an announcement of three bio markers, from Australia, Canada and the United Kingdom (i.e. the British Commonwealth!)

• Canada: “These preliminary results suggest that IL-1α, 6 and 8 adjusted for illness duration may serve as robust biomarkers, independent of age, in screening for ME/CFS.”
• London: “Natural killer cells demonstrated the greatest changes in miRNA expression with up regulation of hsa-miR-99b and hsa-miR-330-3p. These findings are functionally consistent with current understanding of the pathogenesis of CFS/ME.” MicroRNAs hsa-miR-99b, hsa-miR-330, hsa-miR-126 and hsa-miR-30c: Potential Diagnostic Biomarkers in Natural Killer (NK) Cells of Patients with Chronic Fatigue Syndrome (CFS)/ Myalgic Encephalomyelitis (ME) [2016].
• Australia: ” the first to identify circulating miRNAs from ME/CFS patients. They found three distinct miRNAs that might serve as biomarkers.”

Testing against the model

• IL-1 alpha, IL-6, IL-8  – all of these are documented to be effected by probiotics
  • “but a combination of infections followed by cell damage leads to release of the intracellular cytokine interleukin (IL)-1 alpha from endometrial cells, which then acts to scale inflammatory responses.” [2016]
  • “, feeding maize fibre and soyabean fibre raised IL-1α and TNF-α mRNA levels.” [2013]
  • “Lactobacillus rhamnosus GG (LGG).. inhibits activation of …interleukin-1alpha, or gamma-interferon.” [2002]
  • ” mechanism of probiotics by testing effects of IL-α, which is upregulated in the peripheral blood mononuclear cells of Enterococcus  faecium-supplemented piglets,” [2013]
  • ” lactobacillus [Reuteri] inhibited the ETEC-induced expression of proinflammatory transcripts (IL-6 and TNF-α) and protein (IL-6),” [2016]
  • “L. salivarius PS2 intake led to a reduction in milk bacterial counts, milk and blood leukocyte counts and interleukin (IL)-8 level in milk,” [2016]
• hsa-miR-99b and hsa-miR-330-3p
  • Only 4 articles:
    • The hsa-miR-125a/hsa-let-7e/hsa-miR-99b cluster is potentially implicated in Cystic Fibrosis pathogenesis.
    • Differential expression of miRNAs in esophageal cancer tissue [2013].
    • Microrna profiling analysis of differences between the melanoma of young adults and older adults.
    • All of the above are conditions associated with low Vitamin D levels, as is CFS.

Looking at miRNA

• “Our results suggest that 68 bacterial RNAs predicted from 37 different bacterial genomes have predicted secondary structures potentially able to generate putative microRNAs that may interact with messenger RNAs of genes involved in 47 different human diseases.” [2014] i.e. bacteria DNA is adopted into the human cells, producing miRNA.
• “a third mycobacterial species, M. marinum, did express an ∼23-nt small RNA that was bound by RISC and derived from an RNA stem-loop with the characteristics expected for a pre-microRNA.” [2014]

Bottom Line

One set of markers is strongly associated with microbiome shifts. The second with Vitamin D levels.  miRNA can cross from bacteria (including gut bacteria) into human cells. All of these tests appear consistent with the microbiome model

While the tests may help with getting a faster diagnosis, they do not appear to lead to treatments.

I have a friend in the 80’s who for years have been eating using food banks, a lot of prepared/microwaveable meals. Recently a change of circumstance resulted in him moving into a place where food is all made from scratch, often organic.  A lot of his lab tests went from concerning to healthy over 6 months. He does not have CFS, but this does illustrate that diet can have a very major impact. I know that many CFSers survive on food banks in various countries around the world.

Often, one of compounding problems is that a CFS patient is so tired, that all they can do is put a package into the microwave (which can reduce the vitamin and other good content by 50%). Even boiling vegetables in soft water, strips remove nutrients. Overcooked, does the same.

One of the irony that I see is that people will spend money on Inulin capsules, instead of using natural sources (and often bringing other minerals and vitamins with it), for example: Banana, Garlic, Chicory root, Globe artichoke, Jerusalem artichole, Jicama, Onion, wild yam [wiki]

I have posted individually in the past and will attempt to reduce this to a simple reference page without citation (see links below for citations)

What is my daily diet?

I do not keep religiously to it, but this is my ideal pattern

• Breakfast: Either rye bread with butter/ cheese/ and eggs OR porridge with bran added (Not pasturized milk or goat milk)
• Lunch: Crisp break or rye bread with cheese, a banana or other fruit
• Supper: 4 oz of fish or meat, salad (I like Kale) with nuts, one or two of the greens above
• Snacks: Mixed Nuts

References:

• “Compared with milk intake, cheese consumption significantly reduced urinary citrate, creatine, and creatinine levels and significantly increased the microbiota-related metabolites butyrate, hippurate, and malonate.” [2015]
• How do I get there from here!!!???!! — Part Two
• Sorbitol / Glucitol
• Diet Impact on Microbiome
• E.Coli and Green Vegetables
• Migraines, diet and the microbiome
• Roundup and food grown with Roundup
• Peanuts – A recommend part of diet
• Wikipedia FODDMAR list is in the right general direction but their target is different and their reported results to date has been less than ideal.