This post examines four conditions that can be co-morbid, which fits the microbiome model. The differences may  be a combination microbiome strains and DNA SNPs. I have already posted about SNPs associated with MCS in this page (which I just updated).

• MCS – Multiple Chemcial Sensitivity
• EHS – electro-hypersensitivity
• IEI – idiopathic environmental intolerances
• MDAS –  multiple-drug allergy syndrome
  • hyper sensitivity to drugs is common with CFS/IBS/FM
• NS – noise-hypersensitivity (hyperacusis)  – prevalence ~ 3.7% in general population [2016]
  • Associated to Lyme [2002]

“Diagnosis of MCS can be difficult because of the inability to assess the causal relationship between exposure and symptoms. No standardized objective measures for the identification of MCS and no precise definition of this disorder have been established.” [2016]

• MCS affects middle-aged women with comorbidities (chronic pain, fibromyalgia and chronic fatigue)[2016]
  • “relation between noise and odor sensitivity reflects a general environmental sensitivity.” [2013]
  • “The estimated prevalence of MCS was higher among allergic patients than non-allergic participants. People with experience of dwelling in a new house and atopic dermatitis were more at risk of being intolerant to chemicals” [2014]
    • “Chemical Sensitivity Factor was associated with allergies and alcohol use.” [2012]
• “Much of the controversy over the causes of electro-hypersensitivity (EHS) and multiple chemical sensitivity (MCS) lies in the absence of both recognized clinical criteria and objective biomarkers for widely accepted diagnosis…” [2015]
  • “Near 40% had a increase in histaminemia (especially when both conditions were present),”
  • “. Both disorders were associated with hypoperfusion in the capsulothalamic area, suggesting that the inflammatory process involve the limbic system and the thalamus. Our data strongly suggest that EHS and MCS can be objectively characterized and routinely diagnosed by commercially available simple tests”

• ” Positron emission tomography activation studies with several different odorants showed in patients with odor-associated symptoms an odorant-related increase in activation of the anterior cingulate cortex and cuneus-precuneus in comparison with a control group.” [2008]

• “confirming MCS altered (P < 0.05-0.0001) glutathione-(GSH), GSH-peroxidase/S-transferase, and catalase erythrocyte activities.. Severe depletion of erythrocyte membrane polyunsaturated fatty acids with increased ω 6/ ω 3 ratio was confirmed in MCS, but not in EHS…. identified significantly altered distribution-versus-control of the CYP2C19∗1/∗2 SNP variants in EHS, ” [2014] – i..e. this has a DNA component
  • ” high chemical sensitive individuals diagnosed by using Japanese criteria as MCS patients were more significantly associated with SOD2 polymorphisms.” [2013]
  • ” Interestingly, the NOS3 -786TT genotype was associated with increased nitrite/nitrate levels only in IEI patients… the (CCTTT)16 allele discriminates MCS..Here, we first demonstrate that NOS3 -786T>C variant affects nitrite/nitrate levels in IEI patients and that screening for NOS2A -2.5 kb (CCTTT) n polymorphism may be useful for differential diagnosis of various IEI. “[2015]
• ” We identified 183 substances whose levels were beyond the normal detection limit. The most prominent differences included significant increases in the levels of both hexanoic acid and pelargonic acid, and also a significant decrease in the level of acetylcarnitine in patients with MCS.” [2016]
  • “suggest that acetyl L-carnitine 1500 mg/day (500 mg t.i.d.) is also efficacious in improving depressive symptoms, pain, and the quality of life of FMS patients.” [2015]
  • ” these results indicate that LAC may be of benefit in patients with FMS, providing improvement in pain as well as the general and mental health of these patients.” [2007]
  • “. Our data show that administering ALC may reduce both physical and mental fatigue in elderly and improves both the cognitive status and physical functions.” [2008]
  • ” Preliminary evidence of a relation between post-infectious fatigue and mitochondrial dysfunction indicates a complex response involving acetylcarnitine”[2006]
  • “Significant differences in plasma acetylcarnitine [41,42] were reported in CFS, while others found no difference [43,44]. There are several explanations for this discrepancy. One explanation could be that the selection of CFS patients differed. The patients of Kuratsune et al. [41,42] were selected according to the CDC criteria, but Jones et al [43] used the Oxford and CDC criteria.” — bacteria determines symptoms, symptoms determine selection. [2006]
    • “Of the 99 [CFS] patients investigated, 58 reported a decrease in the symptoms by the use of azithromycin. These responding patients had lower levels of plasma acetylcarnitine.”  [2006]
• “Plasma levels of substance P, vasoactive intestinal peptide and nerve growth factor, but not histamine, were elevated in patients with self-reported multiple chemical sensitivity (sMCS). Exposure to volatile organic compounds (VOC) increased plasma levels of all parameters in these patients, while it had no effect in normal subjects or patients with atopic eczema/dermatitis syndrome (AEDS).” [2004]
• ” The phenomenon of electromagnetic hypersensitivity in the form of dermatological disease is associated with mastocytosis. The biopsies taken from skin lesions of patients with EHS indicated on infiltration of the skin layers of the epidermis with mastocytes and their degranulation, as well as on release anaphylactic reaction mediators such as histamine, chymase and tryptase.” [2015]
• “Our data show an increased prevalence of metal allergy and elevation of mercury levels in bio-indicators among patients with MCS.” [2013]
• ” the histamine-releasing activity of plasma from patients with MDAS was significantly increased and correlated with [Hyper coagulation] F(1+ 2) levels (r = 0.68; P = .04).” [2008]

Discussion

Some of the studies suggest (speculate) that the section of the brain that is over activated in a MCS/EHS reaction has become “hard-wired” to over react. This smells of “it’s all in your head and not real” view. Other areas of the brain alteration have been associated with microbiome shifts, so the hard wired aspect or psychological aspect is not probable.

My own experience is that I had mild MCS during one episode which disappeared afterwards. Not 100% disappear, I do notice some reaction to various chemicals in sufficient concentration — but I then remove myself quickly, and the reaction disappear quickly. From this experience, I infer that MCS/EHS may have a significant microbiome dimension. I prefer this view, because it gives hope for treatment and improvement.

I personally deal with two individuals that have MCS and hyperacusis; they also have severe problems with histamine. One of them had a full coagulation panel done just before a bad MCS exposure. Two weeks after the exposure, a second panel was done on this person and the indicator for active coagulation jumped extremely high (i.e. 6 Standard Deviation higher than it was before). Both went through the antibiotic rotations of Jadin without any change of THIS symptoms. Hence, those antibiotics are not good candidates for treating MCS.

Interesting Case

“Immediately after taking 2-3 bites of cooked salmon, a clerical worker developed oral burning, urticaria, and asthma. In the emergency department, she was diagnosed with “allergies”; scombrotoxinism was never considered. She then developed wide-ranging symptoms (e.g., chronic fatigue, asthma, anxiety, multiple chemical sensitivity, and paresthesiae) and saw many specialists (in pulmonology, otorhinolaryngology, allergy, toxicology, neurology, psychology, and immunology). During the next 500+ days, she had extensive testing (allergy screens, brain MRI, electroencephalogram, electromyogram, nerve conduction velocity, heavy metal screen, and blood chemistry) with essentially normal results. She filed a workers’ compensation claim since this injury occurred following a business meal. She was evaluated by a Qualified Medical Evaluator (GL) on day 504, who diagnosed scombrotoxinism.” [2015] [Full Text]

Normally, “Symptoms typically occur within 10–30 minutes of ingesting the fish and generally are self-limited. …. However, symptoms may show over two hours after consumption of a spoiled dish. They usually last for about 10 to 14 hours, and rarely exceed one to two days.”[Wikipedia] In this case, it persisted for over 500 days… with antihistamines being ineffectual.  Morganella morganii is one bacteria that is associated with this condition. ” some M. morganii strains are resistant to penicillin, ampicillin/sublactam, oxacillin, first-generation and second-generation cephalosporins, macrolides, lincosamides, fosfomycin, colistin, and polymyxin B” [Wikipedia]

“Others, especially the Enterobacteriaceae, are contaminants that are introduced post-harvest. It is this second group that is considered most important in the development of histamine.” [Food Safety Watch] Enterobacteriaceae are one family of bacteria that are reported as major overgrowth in CFS.

Treatment Speculations

If you have low acetylcarnitine, then the antibiotic azithromycin (a macrolide) and  acetyl L-carnitine 1500 mg/day (500 mg t.i.d.) may help. Rotation to different macrolides  see macrolide page for a list of them), with Telithromycin and Solithromycin being interesting because they are not widely used (and thus more unlikely to be resistant).

Enterobacteriaceae and M. morganii are suspects. With the high degree of antibiotic resistance, the benefits of doing rounds of (different) antibiotic resistance is questionable. There were no published studies on antibiotics and MCS that I could locate. I could not find any studies using fecal transplants for MCS or EHS — positive results of such studies would likely confirm a microbiome aspect.

Bottom Line

All of these conditions appear to be connected to excessive release of histamine into the body and possibly link back to Enterobacteriaceae overgrowth . This could be normal release coupled with an excessive background level of histamine due to overgrowth of some bacteria, or a mis-signalling for histamine release. Often the body has a Ying/Yang aspect. The signal to release is combined with a signal to constraint. If the signal to constrain is inhibited, excessive histamine may be released.

Hexanoic acid  and pelargonic acid being high may lead to identification of the bacteria because these chemicals  tend to be used as antibacterials against many species. This hints that the bacteria(s) causing this condition produces them against other bacteria.

• “some natural microorganisms have been screened and evolved to produce hexanoic acid,” [2014]

 
An experience
A reader wrote that after a bad MCS exposure,
  she took a full dosage of Mutaflor and Symbioflor-2. She slept hard and almost all of the symptoms were gone afterwards.

Lactobacillus sporogenes is a name that is often incorrectly used when discussing Bacillus coagulans. It is part of a long standing trend to hide the actual ingredients in products by using latin names, former names and other obtuse references. Often you need to get the help of a librarian to actually find out what something is.

• “B. coagulans SL5 produced the maximum amount of histamine” [2013] this a risk for the subset of CFS patients who have histamine issues.

IBS

• Bacillus coagulans significantly improved abdominal pain and bloating in patients with IBS. [2009]
• “There was a significant decrease in the clinical symptoms like bloating, vomiting, diarrhea, abdominal pain and stool frequency in a patient group receiving B. coagulans MTCC 5856 when compared to placebo group (p < 0.01). Similarly, disease severity also decreased and the quality of life increased in the patient group receiving B. coagulans MTCC 5856 when compared to placebo group.” [2016]
• “Bacillus Coagulans improves abdominal pain and diarrhea in IBS patients.” [2014]

Fibromyalgia and CFS – No studies

And nothing on coagulation

• Is killed by oregano [2009], turmeric [1999]

Bottom line

It provides symptom relief for IBS only and is easily killed by herbs and spices. It is unlikely to be a good use of limited funds.

A reader forward this pdf — at first, I suspected a joke — because it was dated April 1,2016. It is not. Symbioflor has been reported effective for improving IBS and also causing patients with ZERO E.Coli to establish an E.Coli population.

There are actually two risks:

• The claims of effectiveness are not sufficient and it is taken off the market in Europe
• The claims of effectiveness are validated, this now makes it a medical drug and thus FDA may attempt to control access to it (for example, preventing shipments to the US — which is what happened with Mutaflor, E.Coli Nissle 1917).

The best outcome is that it is not deemed sufficiently documented (and thus not of interest to the FDA) but is not taken off the market — pending further studies.

If you on sitting on the fence about this probiotic, the opportunity could disappear quickly.

IF YOU HAVE TRIED IT — please post as comments, your response and observations.

A reader asked, what probiotics can I take while taking minocycline. Minocycline and tetracyclines are members of the same family — so the same general rules apply. The good news is that not all probiotics will be killed, the bad new is we do not know which strains will be killed or survive.. Some brands may be 100% kill, other brands perhaps 25-35% will survive.

Bifidobacterium

As many species as possible since most will be killed, but 14% is expected to survive.

• “Bifidobacterium breve, which appeared to be generally more resistant. Potentially acquired resistance was only observed against tetracycline and minocycline, in 14% of the strains.” http://jac.oxfordjournals.org/content/55/1/38.long

• “Susceptibility to trimethoprim, trimethoprim/sulfamethoxazole, ciprofloxacin, clindamycin, tetracycline and minocycline was variable. Thetet gene was responsible for tetracycline resistance in 15 strains including 7 probiotic isolates belonging to the taxa Bifidobacterium animalis subsp. lactis and Bifidobacterium bifidum. ” http://jac.oxfordjournals.org/content/58/1/85.long

Lactobacillus Reuteri

Note: Some commercial L.Reuteri are very sensitive to minocycline according to FDA filings…. being sensitive is a PLUS for the FDA.

• “Acquired resistance percentages to these antibiotics( tetracycline and minocycline) were extremely high for L. crispatus, L. reuteri, L. gallinarum, and L. salivarius subsp. salivarius (75%-100%). L. amylovorus on the contrary, displayed lower resistance percentages (25%) toward minocycline and tetracycline. In several strains, resistance against the tetracycline antibiotics was associated with the presence of the resistance genes tet(K), tet(L), tet(M), tet(W), and tet(Z).” [2006]
• “93 Lactobacillus strains isolated from domestic geese raised on Polish farms… strains were resistant to… 23.6% to tetracycline (MIC ≥ 32 μg/ml), …. 18.3% to doxycycline (MIC ≥ 32 μg/ml),
• “Antimicrobial activity and antibiotic susceptibility were tested for 23 Lactobacillus and three Bifidobacterium strains isolated from different ecological niches… All strains were susceptible to ampicillin, gentamicin, erythromycin and tetracycline.” [2015]

E. Coli

I could not find anything specific for Mutaflor or Symbioflor-2

• “We conducted a study of Escherichia coliisolates obtained from human and food samples to assess the prevalence of antimicrobial resistance and to determine the genotype and clonal relationship of 84 E. coli isolates (48 from humans and 36 from foods). An antimicrobial susceptibility test was performed using the disk diffusion method.All isolates were susceptible to ceftriaxone. Overall, 26%, 20.2%, 15.4% and 6% of the isolates were resistant to tetracycline, ampicillin, sulfamethoxazole/trimethoprim and cephalotin, respectively. [2015]

Prescript Assist and GeneralBiotics Equilibrium

Both of these are very heavy species (150 in combination) so resistance of many species would be expected.

I have been asked this question several times, today on facebook a CFS suffer shared her experience and an article. The two pieces of information resulted in my researching this post.

Experience: “Hi Ken, I’ve been using cannabis for pain and neuroinflamation management for some years now. After feeling a lot better in these aspects I’ve stopped using it and I’m missing some gut relieve I got from it so I decided to check its antibiotic properties as I remembered some traditional uses of cannabis (much less psichoactive in the past) were mostly because of them.”

Research: “showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance.” [2008]

Staphylococcus aureus keeps showing up in connection with CFS and I view it as a probable maintainer of CFS. It also has many antibiotic resistant species. See this blog post.

There are reports of it being effective for Lyme from user groups, but no published studies on PubMed.

PubMed

Antibacterial

• “The latter [cannabis] compound showed moderate anti-MRSa (IC50 10.0 μg/mL), moderate antileishmanial (IC50 14.0 μg/mL) and mild antimalarial activity against Plasmodium falciparum (D6 clone) and P. falciparum (W2 clone) with IC50 values of 3.4 and 2.3 μg/mL, respectively.” [2015]
• ” CBD also displayed powerful activity against methicillin-resistant Staphylococcus aureus (MRSA), with a minimum inhibitory concentration (MIC) of 0.5–2 µg·mL⁻¹ (Appendino et al., 2008)…. CBN demonstrated anticonvulsant (Turner et al., 1980), anti-inflammatory (Evans, 1991) and potent effects against MRSA (MIC 1 µg·mL⁻¹). Pinene is a major component of Sideritis spp. (Kose et al., 2010) and Salvia spp. EOs (Ozek et al., 2010), both with prominent activity against MRSA (vide infra)…. Amongst terpenoids, pinene was a major component of Sideritis erythrantha EO that was as effective against MRSA and other antibiotic-resistant bacterial strains as vancomycin and other agents (Kose et al., 2010). ” [2011]

Coagulation

Coagulation is the suspected cause of much of the neurological symptoms of CFS

• ” The study thus shows that Cannabis sativa and the cannabinoids, THC and CBN, display anticoagulant activity and may be useful in the treatment of diseases such as type 2 diabetes in which a hypercoagulable state exists.”
• “Blood glucose and fibrinolytic activity were significantly increased [by hashish].” [1975]

Bottom Line

There are no suitable studies on PubMed,which means that I cannot clearly recommend it. There is evidence that it could theoretically help because of it’s impact on MRSA and other bacteria as well as coagulation thus I do not have grounds to question it’s use. The CFS suffer experience is consistent with the PubMed studies above.

Talking with a CFS user that have used cannabis, I would suggest using a juicer and making a smoothie out of the leaves. The logic is simple, this will likely result in the best delivery to the gut.

Side-effects of positive results

The obvious ones are to try to get a full coagulation workup, especially for inherited factors. There may be better treatments.

Check for what Staphylococcus species  that are in your system (mouth, bowel) – again, there may be better treatments, possibly ones that could lead to remission.