This last weekend our shipment of Symbioflor-2 (6 strain E.Coli probiotic) arrived. As was the case with Mutaflor (E.Coli Nissle 1917) there was a package insert warning of some side effects. This does not happen with most probiotics — inserts with warnings! A local friend also message me, she has started Mutaflor and had a massive herx for three days and with it passed, she is feeling significantly better. Side effects include:

• ” At commencement of treatment distension of the abdomen, release of wind or upper abdominal pain may occur occasionally.”
• “After the beginning of administration, flatulence is common. Very rarely, undesired effects of the gastrointestinal tract such as abdominal pain, gut noises, meteorism, loose stools or diarrhea, nausea and vomitting may occur. Again very rarely, cases of headache may occur.”

Typically studies start with low dosages and work up

“Symbioflor 2 was administered in standard dosage starting with two times five drops daily and a daily increase by two times one drop until 15 drops daily were reached. Fourteen drops are 1 ml containing 1.5–4.510⁷ viable bacterial counts. The total duration of treatment was 21 days.” [2009]

And yes this probiotic does not come in capsules, but in a droplet bottle! Symbioflor 2 is preferred over Mutaflor (2 capsules = 1 day vs 15 drop = 1 day) because it is easier to slowly increase the dosage.

Why E.Coli Probiotics?

The first question is always why go thru the side effects!!!! The answers are:

• “Escherichia coli (E. coli) bacteria normally live in the intestines of people and animals. Most E. coli are harmless and actually are an important part of a healthy human intestinal tract.” [cdc]
• ” The harmless strains of E.Coli are part of the normal flora of the gut, and can benefit their hosts by producing vitamin K₂,^[5] and preventing colonization of the intestine with pathogenic bacteria.^{[6][7]” [Wikipedia]}
• “In 1885, the German-Austrian pediatrician Theodor Escherich discovered this organism in the feces of healthy individuals.” [Wikipedia]
• Often CFS patients will have ZERO E.Coli in their system
• It is suspected that the bacteria replacing E.Coli are heavy d-lactate acid producers, thus E. Coli probiotics will lower d-lactate levels
• ” E. coli can synthesize all 20 amino acids, all vitamins, all nucleotides, and all fatty acids that it uses during growth and metabolism.” [Course]
• “We pretty much depend upon E. coli in our intestines for our source of Vitamin K and B-complex vitamins.” [Kansas University]
  • Niacin [1954] and NADH – which may be why CFS responds to NADH.

So, the absence of E.Coli result in low levels of Vitamin B (B12, Niacin, etc) and Vitamin K. More important, it has a major role of keeping pathogenic bacteria controlled.

If you stop and think about it — a lot of the abnormal lab results could be caused by the lack of E.Coli…. (speculation!)

Feeding of E.Coli

In earlier posts we saw that sulphur in food (dark green vegetables) encourages the growth of E.Coli or / and MSM. Also d-ribose sugar encourages  the growth of E.Coli (which may be why it helps CFS patients). E.Coli grows best at…. 98.6F (37C)… [Course]

Per earlier posts, it should be taken before meals with some fat. My wife is trying drops of Symbioflor-2 into warm 2% milk (i.e. close to 37C) with a little d-ribose in it.

Do NOT take with C. butyricum MIYAIRISAN Probiotics

“1.1 C. butyricum MIYAIRI antagonistic effects on toxinogenic Escherichia coli and 20 E. coli strains isolated from live stocks (cows, pigs and chickens) were evaluated by the plating method. C. butyricum MIYAIRI inhibited the growth of all E. coli strains tested” [Source]

See also this post on feeding E.Coli with baking soda.

CFS is a disease that is stress sensitive. Stress produces chemicals that appear to increase the population of disruptive bacteria in the gut.

There are potential attitude problems because it implies (to some) that CFS is a psychological condition

• Meditative movement for depression and anxiety. [2013] Qigong (Chi Kung), Taijiquan (Tai Chi) and Yoga ” Results suggest that MM may be at least as effective as conventional exercise or other interventions in ameliorating anxiety and depression; however, study quality is generally poor and there are many confounding factors. This makes it difficult to draw definitive conclusions at this time.”
• “the results suggest that lifestyle (Yoga) intervention may improve clinical condition and personality in patients with CFS.” [2015]
• Isometric yoga improves the fatigue and pain of patients with chronic fatigue syndrome who are resistant to conventional therapy: a randomized, controlled trial. [2014]
• Iyengar yoga for adolescents and young adults with irritable bowel syndrome. [2014] ” a brief IY intervention is a feasible and safe adjunctive treatment for young people with IBS, leading to benefits in a number of IBS-specific and general functioning domains for YA.”
• Efficacy and safety of meditative movement therapies in fibromyalgia syndrome: a systematic review and meta-analysis of randomized controlled trials. [2013] “. Yoga had short-term beneficial effects on some key domains of FMS.”

So for symptom mitigation, it can definitely help — exactly what would be expected from the model. Meditative movement reduces stress and thus the production of chemicals produced by stress.

For remission, zero indication that it would result in any remissions.

Stress Impact

• The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.[2016]
• The gut microbiome and the brain. [2014]
• Acclimatisation-induced stress influenced host metabolic and gut microbial composition change. [2015] “We also observed a strong influence of stress on the host metabolism and commensal compositional variability.”
• The effect of stress on microbial growth. [2014] “. The ability of microorganisms to recognize and produce neurochemicals that can influence the host, known as microbial endocrinology, provides for a mechanistic basis with which to examine the ability of stress to influence health and susceptibility to disease.”
• Does stress induce bowel dysfunction? [2014]

Bottom Line

Most CFS patients need to lower their stress levels, especially those who onset were connected to stressful jobs.  This may be done by adaptogens (Ashwagandha, etc) [See Mother Earth News], adjusting self-expectations and/or ignoring other expectations on you, or by some form of meditative movement. This will not, by itself, cause remission but it should lessen the time to remission and reduce the risk of future relapse once remission is obtained.  If you were an adrenaline junkie, you have a LOT of behavior modification to do.

On the flip side, disability issues, financial issues, non-supportive spouses and families represent severe challenges of sources of stress that can keep a person locked into the CFS cycle — especially with brain fog.

Of course, one of my favorite “medicines” shows up… see my earlier post on this special medicine (which also encourages the growth of bifidobacterium probiotics)

• “Dark chocolate reduced the urinary excretion of the stress hormone cortisol and catecholamines and partially normalized stress-related differences in energy metabolism (glycine, citrate, trans-aconitate, proline, beta-alanine) and gut microbial activities (hippurate and p-cresol sulfate).” [2009]
  • Specific dietary preferences are linked to differing gut microbial metabolic activity in response to dark chocolate intake. [2012]
  • “The milk chocolate snack resulted in the decrease of anxiety in high anxiety trait subjects, whereas dark chocolate and cheese and crackers respectively improved the anxiety level and the energetic state of low anxiety trait participants.” [2012]

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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