In my last post, I looked at a variety of herbs and spices to correct the shift of the microbiome (gut bacteria) seen with CFS. In this post, I am attempting to do a similar summary for probiotics.

Why is this important? Consider Bifidobacterium which is very low in CFS patients. It has been found to “synthesize at least 19 amino acids and (…) all of the enzymes that are needed for the biosynthesis of pyrimidine and purine nucleotides” [2015]  The question of why CFSers are low in various amino acids appears to have an answer.

Similarly, “Lactobacilli and bifidobacteria strains from VSL#3 and Lactobacillus GG did not induce interleukin 8, whereas both cell debris and cell extracts from E. coli Nissle 1917 [Mutaflor] induced interleukin 8 production in a dose-dependent way.”[2002]. E.Coli is extremely low in most CFS patients.

Not just CFS – but likely most autoimmune conditions

This does not apply only to CFS but also Rheumatoid Arthritis[RA] “The signs of 3rd degree dysbiosis [in RA], by reducing the concentration of Bacteroides spp., Bifidobacterium spp., Lactobacillus spp. populations, typical strain E. coli. with [high levels of] Enterococcus (Hly+), Klebsiella spp., Proteus spp., Staphylococcus spp., lactosonegative and E.coli (Hly+) ” [2014]

Persistance

When taking probiotics, you need to be aware that some are “flow thru” and others may take up residence.

“After oral consumption of probiotics, E. coli [Mutaflor] and enterococci [Bioflorin] could be detected in stool samples (57% and 67%, respectively). In contrast, with only one exception, ingested lactobacilli and bifidobacteria could not be detected in human feces.” [2007]

The results for lactobacilli and bifidobacteria may be heavily influence on when and how the later two probiotics are taken as reported in this earlier post.

Strain differences

“In children, L. casei rhamnosus Lcr35, but not L. rhamnosus GG, showed a beneficial effect.” [2010] The literature is very sparse on this information. 😦

Finding PubMed (reliable) literature of probiotic interactions is more time consuming  and difficult then with herbs and spices. I have constructed a table below based on my current findings. Feel free to forward any solid PubMed articles to me that you find to fill in the gaps.

Should I continue with Bifidobacterium and Lactobacilli

The simple answer is yes! But selectively!!!!

• Bifidobacterium probiotics are often mis-identified, so unless it is a single strain, don’t worry about it and change brands regularly. See this post. We want their transitory benefits until the dysfunction is corrected.
• For Lactobacilli — only a few families and strains should be considered. L. Reuteri is one of those. L. Acidophilus should be totally avoided.

Bifiform

During my research, I came across this probiotic shown above. It is available in Denmark, Sweden and eastern European countries. It contains:

• Lactobacillus rhamnosus GG (LGG^®) 100 million cfu**
• Bifidobacterium BB-12® 100 million cfu**
• Thiamin (B1) 0.4 mg
• Vitamin B6 0.5 mg

A reader wrote a comment and link on my Rifaximin post,

“Herbal therapy is equivalent to rifaximin for the treatment of small intestinal bacterial overgrowth”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4030608/

The link has a table of 4 different capsules, each with different herbs.  I have a working model that CFS/FM/IBS is a overgrowth of (Klebsiella, Enterobacteria, Enterococcus,Streptococcus) and very low levels of (E.Coli, Bifidobacterium, Lactobacillus) reported first in 1998.

The advantage of having a model is the ability to estimate probable impact from different herbs, spices, antibiotics etc.

Below, I took each of the herbs and attempt to cross-reference them to their impact on the above bacteria families to see if there are specific ones that are really well suited for CFS. The score is done as follow:

• Overgrowth
  • Effective 1
  • No Info/Weak 0
  • Resistant 0
• Undergrowth
  • Effective -2
  • No Info/Weak -1
  • Resistant 0

Feel free to use your own formula if you disagree.

Undergrowth is more important because those bacterias as they increase will reduce the overgrowth. Killing the overgrowth will leave a vacuum which may well be repopulated with dysfunctional bacteria. The Ideal Herb or spice would be a THREE (3). The best found was a Zero (0)

You must rotate herbs, I have seen this reported in multiple studies:

“In general, the development of adaptation varied according to the bacterial strain and the essential oil … it is important to use essential oils at efficient bactericidal doses in animal feed, food, and sanitizers, since bacteria can rapidly develop adaptation when exposed to sub-lethal concentrations of these oils.” [2015]

There is a single candidate “super” herb/spice (1) . Has any one tried Thyme oil or Thyme mouth wash? Please comment.

• Thyme (Thymus vulgaris)

The best ones (0) are:

• Mastic Gum (Chios Mastic Mastiha) – ideally chewed in the mouth

• Neem (Azadirachta indica)
• Oregano (Origanum compactum/vulgare) – used by the person in the letter I published.
• Olive Leaf (Olea europaea)
• Pau D’Arco (Tabebuia spp)

• Tulsi (Ocimum tenuiflorum)

The second best ones (-1) are:

• Cinnamon ( Cinnamomum verum)
• Ginger (Zingiber Officinale)
• Licorice (Glycyrrhiza glabra)
• Rhubarb (Rheum rhabarbarum)
• Sage (Salvia officinalis)
• Thyme (Thymus vulgaris)
• Wormwood (Artemisia)

The chart is based on whatever could be found. In some cases, some strains were killed and others were resistant. Your response will likely vary to each of the above.

For CLARITY to the brain fogged

• 3 VERY VERY GOOD
• 1 Unusually Good
• 0 Recommended
• -1 Acceptable
• -2 You may be doing more harm than good
• -3 You are shooting craps — we have no solid information on what will happen
• -4 You are probably harming yourself
• -5 You are making yourself worst!

There is an excellent article on more unusual Indian herbs. “The millenarian use of these plants in folk medicine suggests that they represent an economic and safe alternative for treatment of Urinary Tract Infections.” As well as this article.

The Image:

The Table

Lactobacillus Casei is in two specialized probiotic drinks: Yakult and DanActive (Actimel) and is also found in fermented green olives and cheddar cheese. There are over 5000 articles on PubMed.

“Administration of lactobacillus casei prior to an inflammatory insult to the bowel prevents the development of increased intestinal permeability.^{[10][11]” that is, it appears to reduce leaky git.}

Lactobacillus casei Shirota Supplementation Does Not Restore Gut Microbiota Composition and Gut Barrier in Metabolic Syndrome: A Randomized Pilot Study[2015].

“We found a significant rise in both Lactobacillus and Bifidobacteria in those taking the LcS, and there was also a significant decrease in anxiety symptoms among those[CFS Patients] taking the probiotic vs controls” [2009] – dosage was 24 Billion CFU, i.e. 4 bottles per day.

Fermented milk containing Lactobacillus casei strain Shirota prevents the onset of physical symptoms in medical students under academic examination stress [2015].

“Lactobacillus casei strain GG alone did not significantly improve symptoms in this irritable bowel syndrome” [2000] Note this is a different strain than above.

The anti-obesity effects of Lactobacillus casei strain Shirota versus Orlistat on high fat diet-induced obese rats[2015].

I recommend Yakult(click for a post on PubMed articles on this strain) because it has been demonstrated to reduce Anxiety levels in CFS. I know CFSers who can notice in a day or two of forgetting to take it that anxieties start building. Stress and anxiety are associated with relapse in CFS, thus reducing the same may decrease the risk of flares.

If you are using a mixture with L.Casei in it, be wary that it may be a “token amount” and far less than the 40 Billion CFU/day used in the above study.

CFS patients have been reported to be dominantly “Type A” personalities, that is:

• “The theory describes Type A individuals as ambitious, rigidly organized, highly status-conscious, sensitive, impatient, take on more than they can handle, want other people to get to the point, anxious, proactive, and concerned with time management. People with Type A personalities are often high-achieving “workaholics“, push themselves with deadlines, and hate both delays and ambivalence.^[4]“

Later this wikipedia article states

• “An analysis of the literature suggests the possible role of Mg deficiency in the susceptibility to cardiovascular diseases, observed among subjects displaying a type A behavior pattern. Experimental data which support this hypothesis are reviewed. Type A subjects are more sensitive to stress and produce more catecholamines than type B subjects. This, in turn, seems to induce an intracellular Mg loss. In the long run, type A individuals would develop a state of Mg deficiency, which may promote a greater sensitivity to stress and, ultimately, lead to the development of cardiovascular problems.^[23]“

Looking at the literature for CFS we find 48 articles on PubMed dealing with Magnesium and CFS. As far back as 1991 (25 years ago), magnesium supplementation was found to have significant impact on CFS patients.

• “20 patients with CFS had lower red cell magnesium concentrations than did 20 healthy control subjects matched for age, sex, and social class (difference 0.1 mmol/l, 95% confidence interval [CI] 0.05 to 0.15). In the clinical trial, 32 patients with CFS were randomly allocated either to intramuscular magnesium sulphate every week for 6 weeks (15 patients) or to placebo (17). Patients treated with magnesium claimed to have improved energy levels, better emotional state, and less pain, as judged by changes in the Nottingham health profile. 12 of the 15 treated patients said that they had benefited from treatment, and in 7 patients energy score improved” [1991]

There has been two studies

• “Type A behaviour, coping strategies …between chronic fatigue and irritable bowel syndrome patients prior to illness and between these groups and healthy controls.”
• “CFS patients’ mean score on the JAS[A test for Type A Personality] was 5 points higher than that of the general population (healthy controls)” [2009]

As well as similar results:

• “For 57 Chinese American individuals initially diagnosed with CFS, those who recovered after one year reported lower levels of life stress than those who did not recover.” [2003]

Hypothesis: Stress behavior is Microbiome Related

This includes Type A Personality. There is actually some literature that seems to support it:

• Gut microbiome composition is associated with temperament during early childhood[2015].
• “Understanding microbiota-brain interactions is an exciting area of research which may contribute new insights into individual variations in cognition, personality, mood, sleep, and eating behavior, and how they contribute to a range of neuropsychiatric diseases ranging from affective disorders to autism and schizophrenia.” [2015]
• “there is now expanding evidence for the view that commensal organisms within the gut play a role in early programming and later responsivity of the stress system.” [2014]
• “suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain.” [2012]

Treating Stress And Anxiety

If we assume that the above hypothesis is true, then we should find studies where taking probiotics etc. measurably reduces stress. We do.

• “these results suggest that consumption of fermented foods that contain probiotics may serve as a low-risk intervention for reducing social anxiety.” [2015]
• Yakult – 4 bottles/day – “Decrease in Anxiety symptoms [Score reduced by 50%] for CFS patients[2015] [2009]
  • Fermented milk containing Lactobacillus casei strain Shirota prevents the onset of physical symptoms in medical students under academic examination stress[2015].
• “These results suggest that chronic ingestion of L. Plantarum PS128 could ameliorate anxiety– and depression-like behaviors and modulate neurochemicals related to affective disorders.”[2015]
• “Lactobacillus rhamnosus (JB-1) … promotes consistent changes in GABA-A and -B receptor sub-types in specific brain regions, accompanied by reductions in anxiety and depression-related behaviors.”[2016] [2011]

Similarly, supplements that are known to reduce stress would also exhibit some antibacterial impacts. The most common ones are the Adaptogens:

• Ashwagandha
  • An alternative treatment for anxiety: a systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera)[2014].
  • Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence[2013].
  • A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults[2012].
  • “W. somnifera exhibited significant antibacterial activities against Gram-negative bacteria, particularly S. typhi.”[2012]
• Rhodiola Rosea Root (Rosavin)
  • Decrease in the level of psychic fatigue and situational anxiety, [The effect of the preparation rodakson on the psychophysiological and physical adaptation of students to an academic load]. [2000]
  • “concluded that repeated administration of R. ROSEA extract SHR-5 exerts an anti-fatigue effect that increases mental performance, particularly the ability to concentrate, and decreases cortisol response to awakening stress in burnout patients with fatigue syndrome.” A randomised, double-blind, placebo-controlled, parallel-group study of the standardised extract shr-5 of the roots of Rhodiola rosea in the treatment of subjects with stress-related fatigue.[2009]
• Magnolia Bark [honokiol]
  • “It has therapeutic potential in anxiety, pain, cerebrovascular injury, epilepsy, and cognitive disorders including Alzheimer’s disease.”[2013]
  • Antimicrobial effect of Magnolia officinalis extract against Staphylococcus aureus.[2011]
  • Antifungal activity of magnolol and honokiol[2000]
• Jujube Fruit
  • “Investigation of the antimicrobial activities of Snakin-Z, a new cationic peptide derived from Zizyphus jujuba fruits[2013].
  • “[Effects of Semen Ziziphi Spinosae on the anxiety behavior of the yin deficiency mice] [2008].

Personal observation: Clostridium butyricum(Miyarisan probiotic) has been reported to reduce stress levels considerably. While there are no studies on it and anxiety, I would advocate it in addition to the above. This effect may be unique to CFS patients because of their specific dysfunctions.

The reason is simple, it produces butyrate / butyric acid which is a GABA analogue:

• “Benzodiazepines (BZDs) are a class of drug that is presumed to indirectly promote gamma-amino butyric acid (GABA) activity and rapidly control the core symptoms associated with Generalized Anxiety Disorder.”[2014]

“Recently, an increased intake of highly processed, low-fibre food products rich in simple sugars has been observed, resulting in low levels of butyrate production in the intestinal lumen.” [2013] This shift may account for multiple increases of conditions and also suggests that high-fibre food is essential.

Bottom Line

It is well known that stress and anxiety triggers CFS flares. Reducing anxiety with probiotics and selected herbs is beneficial and may contribute towards a microbiome shift that could lead to remission.

Rifaximin is an antibiotic that does not enter the body. Rifaximin is used in the treatment of traveler’s diarrhea (which is also the use of Mutaflor, Myrisan and other probiotics) and would have significant potential with CFS. While there has been no PubMed studies with CFS, there has been some for IBS which I view as a different manifestation of the same condition.

• “Although rifaximin had significant improvement in symptoms of IBS over placebo, it is notable that only 40.7% patients had a response to treatment with a small incremental benefit compared with 31.7% improvement in placebo group.[2] Treatment for IBS with rifaximin should be prudent.” [2014]
• “Clinical studies have demonstrated that rifaximin improves symptoms associated with IBS, such as bloating, flatulence, stool consistency, and abdominal pain, and has a side-effect profile similar to placebo..additional investigation into optimal dosing, treatment duration, and potential resistance is required”[2015]

The above article summaries results. It results in improvement and not remission.

The model that I use for CFS/FM/IBS is overgrowth of (Klebsiella, Enterobacteria, Enterococcus,Streptococcus) and very low levels of (E.Coli, Bifidobacterium, Lactobacillus) reported first in 1998. Looking at the profile reported in a 2013 article, rifaximin inhibited in vitro:

• 85.4% of Escherichia coli (BAD)
• 43.6% of Klebsiellaspp., (Good – but too little)
• 34.8% of Enterobacter spp (Good – but too little)
• 54.5% of other Enterobacteriaceae spp., (Good – but too little)

A 2014 study reported

• Active against 96.9% diverse Enterobacteriaceae and
• 90% of Campylobacter spp. were resistant

This appears consistent with the results reported above– some improvement would be expected but the core shifts would not be corrected.

Checking the general web, I find in this post:

“Usage amongst ME/CFS Specialists

Dr. De Meirleir uses Rifaximin on patients based on test results, including this dysbiosis test. He sometimes combines it with other antibiotics depending on test results and recommends the Rifaximin be followed by a 23 day course of the probiotic VSL#3

Dr. Teitelbaum believes that all ME/CFS patients be at least tested for SIBO. He writes about his theories of SIBO here.

Dr. Peterson seems to prescribe Rifaximin to a number of his patients with some taking the probiotic VSL#3 after the Rifaximin course.

Dr. Myhill recommends Rifaximin to some patients. Although she has a different dosing strategy to most, involving 200mg 3x a day for 3 days followed by a maintenance dose of 200mg daily. She also incorporates a hydrogen sulphide urine test to monitor progress.  She elaborates on this here.”

Benefit/Risk Odds

For rifaximin, “The overall eradication rate according to intention-to-treat analysis was 70.8%…The overall rate of adverse events was 4.6%… improvement or resolution of symptoms in patients with eradicated SIBO was found to be 67.7%”[2017]

• “Although the rifaximin group showed a greater percentage of global symptom improvement, this was limited to bloating, as scores for abdominal pain, diarrhea, and constipation did not improve significantly.”[2007]

Bottom Line

In my ranking of antibiotics, it is reasonable but still not ideal as shown below. It is not part of a cure but looks like a reasonable compliment to tetracyclines and macrolides to be given concurrently.