Enterogermina – Four Bacillus clausii Strains

A niece happen to be vacationing in Italy and every time that a friend or family goes to a different country, I start looking for established probiotics that may be marketed only in that country which has PubMed studies. Enterogermina in Italy is one such treasure (in theory). Originally, the species was classified as Bacillus subtilis, which was later corrected to Bacillus clausii [“Bacillus clausii sporulated strains are actually used in the treatment of gastrointestinal illnesses to restore intestinal flora because of their antibiotic resistance and ability to stimulate immune activity…They have shown that B. clausii in Enterogermina can in fact colonize for brief periods of time on the intestinal wall of the gut, and provoke immune response in mice to rid of pathogenic bacteria. “]

https://www.enterogermina.it/ is their site. It does not require refrigeration, thus nice for mailing around the world. (As a FYI, back in 2000, I arranged with a CFS patient in the Czech republic to buy and send my Piracetam tablets — they were over the counter there and not obtainable in the US. I paid her 2x her cost for the effort. We were both happy!)
There are 9 studies on PubMed on this specific brand and 83 studies on Bacillus clausii (B. clausii strains (OC, NR, SIN, T) typically)
  • Bacillus clausii treatment showed a significant decrease of IL4 levels (p=0.004) and a significant increase of IFNgamma (p=0.038), TGFbeta (p=0.039), and IL10 (p=0.009) levels. In conclusion, this study shows that the Bacillus clausii may exert immuno-modulating activity by affecting cytokine pattern in allergic subjects and confirms previous study conducted in allergic children. [2005]
  • “In conclusion, this study shows that the B. clausii may exert immunomodulating activity by affecting cytokine pattern at nasal level in allergic children with recurrent respiratory infections.” [2004]
  • “DNA led to the finding that all of the Enterogermina strains belong to a unique genospecies, which is unequivocally identified as the alkalitolerant species Bacillus clausii…in contrast to several reference strains of B. clausii, the strains constituting Enterogermina are characterized by a notable low level of intraspecific genome diversity and that each strain has remained the same for the last 25 years.” [2001]
  • “This review describes the therapeutic activity of Bacillus subtilis spores (Enterogermina) in the treatment of intestinal disorders associated with alterations in the qualitative and quantitative composition of the normal human intestinal flora.” [1994]
  • “The immunomodulatory and stabilizing effect of Bacillus subtilis spores on the intestinal flora is probably responsible for this improvement.” [1985]
  • “We examined two commercial B. subtilis probiotic preparations, Enterogermina and Biosubtyl. Surprisingly, physiological and genetic characterization of the bacteria contained in each of these preparations has shown that neither contains B. subtilis.” [1999]
  • Bacillus clausii spores survive transit through the human gastrointestinal tract. They can undergo germination, outgrowth and multiplication as vegetative forms. Bacillus clausii strains can have different ability to survive in the intestinal environment.” [2015]
  • “B. clausii strains release antimicrobial substances in the medium. Moreover, the release of these antimicrobial substances was observed during stationary growth phase and coincided with sporulation. These substances were active against Gram-positive bacteria, in particular against Staphylococcus aureus, Enterococcus faecium, and Clostridium difficile.” [2004]
  • Bacillus clausii as a treatment of small intestinal bacterial overgrowth [2009].

Bioflorin – Enterococcus faecium SF 68

This is the latest discovery of an unusual probiotic, it is used for acute adult diarrhea. Availability is in Germany (unfortunately Amazon.de does not carry it). On line German pharmacies do,  for example at this site.

What do we know about it? There are 13 PubMed articles:

  • “Probiotic enterococci a widely used by pediatricians and infection diseases doctors in Russia as means for the treatment of dysbiosis, irritated bowel syndrome and in the treatment and prevention of different functional and chronic intestinal diseases. Strains E. faecium M74 and E. faecium SF-68 are included in several probiotic drugs and have been proved as effective and safe.” [2013]
  • “Enterococcus faecium SF 68 (sensitive to penicillin, tetracycline, virginiamicin and tylosin, but resistant to streptomycin)” [1994]
  • “An antagonistic activity of Enterococcus faecium SF 68 towards Plesiomonas shigelloides, Aeromonas sp., enteropathogenic Escherichia coli and Yersinia enterocolitica has been studied and demonstrated.’ [1990]
  • Efficacy of SF 68 in the treatment of acute diarrhea. A placebo-controlled trial.[1996]

  • “All treatments were continued for 7 days. Enterococcus SF 68 was shown to be effective in reducing the incidence of antibiotic-associated diarrhoea in comparison with placebo (8.7% compared with 27.2%, respectively). Patients with acute enteritis showed a significantly faster resolution of bowel abnormalities during treatment with Enterococcus SF68 compared with placebo.” [1989]

NOTE: It appears to be available in the US as a probiotic for dogs — “FORTIFLORA® CANINE NUTRITIONAL SUPPLEMENT”


Miyarisan (Clostridium butyricum) – Revisited

When I last looked at Miyarisan, it was available in Japan only. In the last month I discovered that it is now available in the US and EU — thus it is a good time to revisit it.

2020 Update

One of the characteristics that is connected with a lot of the stuff that my model suggests, is that they are often used for diarrhea and other digestive discomfort. In other words, been show effective against common disruptive bugs in the gut. Mutaflor (E.Coli Nissle 1917) and Miyarisan are both traditionally used for that — not as regular daily probiotics, but as probiotics when symptoms require the gut to be fixed. The interesting aspect is this:

  • Mutaflor — the only E.Coli probiotic (and many E.Coli are nasty)
  • Clostridium butyricum – the only Clostridium probiotic that I am aware of (and many Clostridium are Difficult (i.e. difficile))

Clostridium butyricum MIYAIRI 588® (CBM 588®), an anaerobic spore-forming bacterium, has been developed as a probiotic for use by humans and food animals.

Do NOT take with E.Coli 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]


  • “Reduced anxiety levels from 19.8 to 10.2 in the HAMA Attenuated the increase in CRF and HR pre op” [2015] [2014]


This probiotic produces butyric acid (BTA) which is a histamine antagonist [source].

“An important mechanism by which butyrate causes biological effects in colon carcinoma cells is the hyperacetylation of histones by inhibiting histone deacetylase” [2011]

“In humans, the effects of BA can be subdivided into intestinal and extra-intestinal. Intestinal effects include: regulating transepithelial transport, improving the inflammatory and oxidative states of the intestinal mucosa, reinforcing the mucosal barrier, modulating visceral sensitivity and motility, and preventing and inhibiting colon carcinoma. Extraintestinal effects are less well known; they have been studied in vitro and in animal models and sometimes even in humans. Currently investigated effects include: haemoglobinopathies, hypercholesterolaemia, reducing resistance to insulin (in animal studies), and reducing ischemic stroke (in animal studies).” [2012][2011]

Butyrate Studies with IBS

Butyrate is produced by Miyarisan.

“Butyrates represent a potential new IBS therapy. To date, a few trials have been performed to evaluate the effectiveness of sodium butyrate on clinical symptoms and quality of life in patients with IBS. Banasiewicz et al. performed a double-blind, randomized, placebo-controlled study in which 66 adult patients with IBS received microcapsulated butyric acid at a dose of 300 mg per day or placebo as an adjunct to standard therapy. At four weeks, there was a statistically significant decrease in the frequency of abdominal pain during defecation in the butyric acid group (p = 0.0032). At 12 weeks, decreases in the frequency of spontaneous abdominal pain (p = 0.0132), postprandial abdominal pain (p = 0.0031), abdominal pain during defecation (p = 0.0002) and urge after defecation (p = 0.0100) were observed [9, 10]. In a preliminary report, Tarnowski et al. demonstrated an improvement of abdominal pain, abdominal discomfort and defecation rhythm in patients with IBS treated with microcapsulated sodium butyrate for 6 weeks, compared to those treated with placebo. In the same study, higher quality of life was noted in patients treated with butyrate [11].” [2013]

Addendum on Brain Injury

Personal Observations

Both my wife and I found we slept hard when we started taking this. By hard, I mean sleeping thru four(4) alarm clocks. For myself, I woke with less adrenalin than usual, more relaxed. As usual, your experience may be different due to different microbiome.

An unusual probiotic: Advanced Orthomolecular Research Probiotic-3

Finding probiotics free of lactobacillus is a challenge. This probiotic is not available in Canada, but fortunately most Canadians live close to the border with the US.

Probiotic-3 contains:

So what do we know about these species/strains? (My earlier notes are here)

Clostridium butyricum

Bacillus mesentericus

A lot of this literature comes out of Russia/East Europe.

Streptococcus (Enterococcus) faecalis

Bottom Line

While there have not been studies for it’s effect on CFS, there is one study showing that it improves IBS (co-morbid with CFS often), and very good results for UC.

Vivomixx Probiotic – A review

Update – Feb 2016

A reader raised the issue if Vivomixx and VSL#3 are actually the same. She was unable to clarify this via Mr. Google. On VSL#3, see this 2017 review — it does not have any evidence of being beneficial for CFS/FM/Etc.

According to this site VSL#3 was renamed Vivomixx in New Zealand.

Vivomixx Clinical Trial NCT02508844Vivomixx Clinical Trial NCT02508844

Vivomixx® 112.5 Billion CFU / Capsule

  • Bifidobacterium breve,
  • Bifidobacterium longum,
  • Bifidobacterium infantis,
  • Lactobacillus acidophilus,
  • Lactobacillus plantarum,
  • Lactobacillus paracasei,
  • Lactobacillus bulgaricus and
  • Streptococcus thermophilus

According to the VSL#3 site. 8 strains of live freeze dried bacteria [112.5 billion CFU] containing

  • Bifidobacterium breve,
  • Bifidobacterium longum,
  • Bifidobacterium infantis,
  • Lactobacillus acidophilus,
  • Lactobacillus plantarum,
  • Lactobacillus paracasei,
  • Lactobacillus bulgaricus and
  • Streptococcus thermophilus.

They are the same product under two different names.


A user asked about a specific (expensive) probiotic for histamine issues. It is produce in Switzerland and thus available to European readers, in the US it appears to be called VSL#3.

What I am going to do for this review is to decompose this blend into it parts, then research each part.

First, on the good side — the specific strains are listed (if specific strains are not listed, then probiotics are usually high risk and should be avoided until there are studies for the actual product!)

Query #1:

  • Are there any pubmed studies for this specific brand product? The answer is NO.
    Screen Shot 2015-06-14 at 5.23.50 PM
  • Decompose into strains in a table
Strain Pubmed for Histamine
Streptococcus thermophilus DSM 24731,
  • nothing for strain.
  • “a total of 69 Streptococcus thermophilus strains screened, two strains, CHCC1524 and CHCC6483, showed the capacity to produce histamine.” [2010] – likely neutral.
bifidobacteria (B. breve DSM 24732,
  • nothing for strain
  • nothing for species
B. longum DSM 24736,
  • nothing for strain
  • nothing for species
B. infantis DSM 24737
  • nothing for strain
  • nothing for species
Lactobacilli acidophilus DSM 24735,
  • nothing for strain
  • nothing clear for species
L. plantarum DSM 24730,
  • nothing for strain
  • “Lactobacillus plantarum Tensia did not produce potentially harmful biogenic amines, such as histamine”[2012]
  • Appears to be histamine neutral
L. paracasei DSM 24733,
  • nothing for strain
  • Suggestion that some of the species may produce histamine [2011]
L. delbrueckii subsp. bulgaricus DSM 24734
  • nothing for strain
  • nothing for species


VSL#3, the alternative name has a variety of benefits for: Pouchitis, Ulcerative colitis, IBS and Allergy

Bottom line

Nothing suggests that it would produce histamines. Alternatively there is no public published peer-reviewed information on PubMed suggesting any positive impact from any of the strains. Recommendation — you are paying to toss some dice with a real possibility of zero benefit. See https://atomic-temporary-42474220.wpcomstaging.com/2016/07/10/first-survey-results-on-probiotics/ for experience. I will add this in the next survey list.

Post Script

A reader pointed out that Vivomixx is also known as VSL #3.  This lead to just one article being found:

  • “Oral therapeutic administration of VSL#3 to ST-sensitized mice significantly reduces symptom score and histamine release in the faeces following allergen challenge, as well as specific IgE response.” [2011]