Tag Archives: diarrhea

More Butyrate Series, Part 8: Clostridium butyricum to Prevent Pathogenic Infections (C. diff, E. coli, H. pylori, and Candida), Leaky Gut, and Tube Feeding Diarrhea

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When would a person consider adding Clostridium butyricum to their health plan? That’s what I’m exploring as I continue to write up what I discovered from scientific studies about Clostridium butyricum. Today will finish up exploring the gastrointestinal studies. You may read more that I have written about Clostridium butyricum here and here. I try to write in simple terms while still maintaining medical accuracy. If you see a typo or mis-information, please point it out! I really appreciate the opportunity to fix it. If you just don’t understand something and really want to, I enjoy questions and do my best to answer them as thoroughly as I can.

Please remember this is not medical advice. Probiotics are still supplements, and supplements can have deleterious effects on health, either directly, by interactions, or even because of their fillers (and commercial forms of Clostridium butyricum seem to have lactose and/or potato starch). As you search for health, don’t forget certain human health necessities: sleep; movement; sunshine; nature; strong, nurturing relationships; freedom from an unforgiving and hateful heart; and self-acceptance. I feel there are more, but I’ll stop there for now. I’m always floored at how we will search for health in a pill or diet while neglecting these basic requirements.

 

Clostridium butyricum to prevent pathogenic infections from other organisms: Escherichia coli 0157:H7, Helicobacter pylori, and Candida

When given prophylactically, Clostridium butyricum prevented death from enterohemorrhagic Escherichia coli 0157:H7 in 100% of mice. [I’m always fascinated by studies with “100% results.”]

Enterohemorrhagic Escherichia coli 0157:H7 is a dangerous human pathogen which can lead to significant bloody diarrhea, kidney failure, and death. Germ-free mice were inoculated with the virulent bacterial strain Escherichia coli 0157:H7. Mice who received no Clostridium butyricum probiotic ALL died from entrohemorrhagic E. coli complications. When given the probiotic prophylactically before receiving the virulent E. coli strain, 100% of the mice survived. If the Clostridium butyricum was given two days into the infection rather than prophylactically, then 50% died.The probiotic used was Clostridium butyricum MIYAIRI 588 strain.

Source: Takahashi, M., Taguchi, H., Yamaguchi, H., Osaki, T., Komatsu, A. and Kamiya, S. (2004), The effect of probiotic treatment with Clostridium butyricum on enterohemorrhagic Escherichia coli O157:H7 infection in mice. FEMS Immunology & Medical Microbiology, 41: 219–226.

In vitro co-culture and cell-to-cell contact of Clostridium butyricum  MIYAIRI 588 and Clostridium difficile greatly decreased and even negated the cellular toxicity of Clostridium difficile toxin.

Both Clostridium difficile andClostridium butyricum are Gram-positive, spore-forming bacteria, but Clostridium butyricum grows faster and uses a wider range of substrates, while also producing butyric acid (butyrate) and a bacteriocin (a microbial “antibiotic”). Researchers found that Clostridium butyricum diminished the cytotoxicity of Clostridium difficile and explored why:

  • Clostridium butyricum cells themselves needed to be present to prevent the cytotoxicity from Clostridium difficile. Using supernatant (fluid with no actual bacterial cells but still with the substances excreted/secreted from the bacteria) from Clostridium butyricum culture did not reduce cytotoxicity or reduce the growth of Clostridium difficile, neither did simply separating the two bacterial cultures by a permeable membrane (but impermeable by the bacteria themselves–so basically having the cells together in proximity with the same environment, but without the cells themselves being able to touch each other).
  • Clostridium butyricum blocked Clostridium difficile‘s germination, perhaps by increasing the amount of organic acids present, such as butyric acid. Clostridium butyricum cultures produce a pH of about 4.8, while Clostridium difficile cultures exhibit a pH of about 6.2, which is similar to the gut’s pH. Co-cultures of the two bacteria together produced a lower pH, which may affect the growth of C. diff and deteriorate the function of one of its toxins, toxin B.

Source: Woo TD, Oka K, Takahashi M, Hojo F, Osaki T, Hanawa T, Kurata S, Yonezawa H, Kamiya S. Inhibition of the cytotoxic effect of Clostridium difficile in vitro by Clostridium butyricum MIYAIRI 588 strain. J Med Microbiol. 2011;60:1617–1625.

A very small human study reported that patients given antibiotic therapy to eradicate Helicobacter pylori had detectable fecal Clostridium difficile toxin A, BUT double doses of Clostridium butyricum Miyairi 588 strain prevented detection of any fecal Clostridium difficile toxin A, indicating that a higher dose of Clostridium butyricum may help prevent antibiotic associated C. diff colitis.

When antibiotics are given, it disrupts the normal suppression of Clostridium difficile (which can live in a healthy person’s gut) in the GI tract, allowing diarrhea or even C. difficile pseudomembranous colitis to occur. Researchers looked for toxin A from C. difficile bacteria when patients were treated with antibiotics alone to eradicate H. pylori or treated with antibiotics and Clostridium butyricum probiotic. A “regular” dose of Clostridium butyricum probiotic did not prevent Clostridium difficile toxin A detection, although it seemed to decrease when compared to the control using no probiotic.  However, doubling the dose of probiotic prevented C. difficile toxin A detection. Specifically MIYA-BM was used and it has 10^7 colony forming units (CFU) per tablet. A “regular” dose was six tablets and a double dose was 12 tablets.

Source: Microbiology and Immunology. Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota. Kyoto Imase, Motomichi Takahashi, Akifumi Tanaka, Kengo Tokunaga, Hajime Sugano, Mamoru Tanaka, Hitoshi Ishida, Shigeru Kamiya and Shin’ichi Takahashi. Volume 52, Issue 3, Version of Record online: 8 APR 2008

In vivo and in vitro testing indicated that Clostridium butyricum Miyairi 588 strain could inhibit, and often eradicate, Helicobacter pylori growth and presence in germ free mice.

This study suggests an antagonistic relationship between Clostridium butyricum and Helicobacter pylori.

  • In  vitro, the butyric acid produced by C. butyricum inhibited H. pylori growth in a direct manner, no matter what the pH, indicating that butyric acid itself was antibacterial. (In contrast, lactic acid also inhibited H. pylori, but not when the pH was adjusted, indicating the effect was pH induced rather than directly from the lactic acid itself.)
  • Pre-incubation of cells with the probiotic inhibited the binding ability of H. pylori to a gastric-mucosal type line of cells.
  • In mice with persistent H. pylori infection, Clostridium butyricum resulted in a rapid reduction of H. pylori and then eventually after three weeks, elimination.

Source: J Med Microbiol. 2000 Jul;49(7):635-42. Studies of the effect of Clostridium butyricum on Helicobacter pylori in several test models including gnotobiotic mice. Takahashi M, Taguchi H, Yamaguchi H, Osaki T, Kamiya S.

Clostridium butyricum Miyairi 588, when given prophylactically to mice, decreased mortality from systemic Candida albicans. 

The mice were pre-treated for three days intraperitoneally with heat-killed C. butyricum and then inoculated intravenously with a virulent strain of Candida albicans. There was significant increase in survival at all doses of the administered C. butyricum, indicating anti-candidal activity.

Source: Hour-Young, Chen & Kaneda, Satoru & Mikami, Yuzuru & Arai, Tadashi & Igarashi, Kazuei & Saito, Masayoshi & Miyoshi, Takeyoshi & Fuse, Akira. (1987). Protection activity induced by the bacterial vaccine, heat-killed Clostridium butyricum against Candida albicans infections in mice.. Japanese Journal of Medical Mycology. 28. 262-269. 10.3314/jjmm1960.28.262.

Might help to reverse leaky gut (increased gastrointestinal permeability)

Clostridium butyricum use in a mouse model of obesity and insulin resistance showed parameters that might be relevant to improving leaky gut (increased gastrointestinal permeability).

Researchers in China wanted to explore the effect of Clostridium butyricum (strain: CBO313.1) on high fat diet obesity and insulin resistance in mice, speculating that short chain fatty acid production and colon barrier functions contribute to these inflammatory-type conditions. They found that the use of Clostridium butyricum:

  • Reduced colon permeability by upregulating the tight junction (TJ) proteins (claudin-1 and occludin)
  • Contributed to a decreased circulating endotoxin level (LPS)
  • Suppressed adipose inflammation
  • Suppressed high fat diet induced low grade colitis
  • Increased short chain fatty acid production in the colon
  • Restored impaired colon permeability

Source: Shang H, Sun J, Chen YQ (2016) Clostridium Butyricum CGMCC0313.1 Modulates Lipid Profile, Insulin Resistance and Colon Homeostasis in Obese Mice. PLoS ONE 11(4): e0154373. https://doi.org/10.1371/journal.pone.0154373

To prevent tube feeding diarrhea

In elderly patients who developed diarrhea in response to required long-term tube feedings, giving Clostridium butyricum to the patients normalized their stool.

The study is written in Japanese, so I have no further details.

Source: Ito, Hayashi, Iguchi, Endo, Nakao, Nabeshima, Ogura. Effects of administration of Clostridium butyricum to patients receiving long-term tube feeding. Jpn. J. Geriat. 34. 298-304. 1997.

Closing

That’s all for today. Do take care. Do look for things you can change in your life without a pill. Move more. Get outside more. Without squashing your own self, get along better with others. Your thoughts are your “inner stew.” They’re what you eat every single moment. Explore them. They make a HUGE difference to health.

Terri F.

More Butyrate Series, Part 8: Clostridium butyricum and Ulcerative Colitis, Irritable Bowel Syndrome, and Antibiotic Associated Diarrhea

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Clostridium butyricum, a soil-based probiotic used commonly in Asia, colonizes the gastrointestinal (GI) tract of about 10-20% of the human population. Although it does produce butyrate in the GI tract, studies show it creates beneficial effects independently of butyrate too. I do not endorse Clostridium butyricum supplements. I became interested in learning about them because I’m interested in the effect of butyrate on slow colon motility. When I started reading about Clostridium butyricum, it sounded like a nice little probiotic, to the point that I have expanded Part 8 of my Butyrate Series much more than I anticipated in order to elaborate on Clostridium butyricum. (See the first post of Part 8 here.)

I’d like to highlight studies on Clostridium butyricum’s use for GI diseases in this and the next post (or two). Please, remember, I am NOT recommending this probiotic for anyone. I just enjoy reading, researching, and compiling information on niches I am learning about. Do NOT use anything on this blog as medical advice, even if I seem nice, honest, and have certain initials after my name. Anyone on the internet can feed you a line.

By all means, if you think Clostridium butyricum sounds right for you, print off the studies I cite, highlight important points, and hand them to your healthcare provider to see what they think. Although most of the information I have read about Clostridium butyricum, both scientifically and anecdotally, has been positive, I have read tidbits where it made some people worse. (Please pay attention. The Clostridium butyricum probiotics I have found have lactose in them and potato starch, which I know many readers are sensitive to.)

And, as always, please help me with typos or incorrect information. And because it’s more important than anything, be kind and gracious from your heart to all. This world is hurting.  And…now back to science.

Ulcerative colitis

Clostridium butyricum (Bio-Three brand) promoted remission in refractory ulcerative colitis patients, particularly if they started the study with low fecal Bifidobacteria counts.

Twenty refractory ulcerative colitis patients received Bio-Three, nine tablets daily for a month.

  • Nine of the 20 (45%) patients went into remission
  • Two of 20 had a positive response but not full remission
  • In total, 55% had clinical and endoscopic improvement.
  • Nine had no response or worsened. (One of 20 became worse.)
  • 10 of the 20 patients also received 100 grams of “fiber,” which seemed to make no difference in any parameter.
  • Response to the probioitic was not correlated with initial severity of disease symptoms. A person with “terrible” ulcerative colitis symptoms could do–or not do–as well on the probiotic as someone with “mild” symptoms .
  • Patients’ fecal biomes were able to be categorized into three distinct clusters, and those in the clusters with lower Bifidobacteria seemed to respond better to the probiotic and had improved fecal microbiota profiles after therapy.

Source: Clinical effectiveness of probiotics therapy (BIO-THREE) in patients with ulcerative colitis refractory to conventional therapy. Yukiko Tsuda, Yasushi Yoshimatsu, Hiroshi Aoki, Kentaro Nakamura, Masaki Irie, Katsuyuki Fukuda, Nobuo Hosoe, Nobuo Takada, Koji Shirai & Yasuo Suzuki. Scandinavian Journal of Gastroenterology. Vol. 42 , Iss. 11, 2007.

Clostridium butyricum (Bio-Three brand) maintained clinical remission better than placebo did in already controlled ulcerative colitis patients over the course of a year, although the results were not statistically significant.

Of forty-six patients, half received three tablets of Bio-Three three times daily and the other half received placebo doses instead.

  • At three months, the relapse rates in the probiotic therapy group was 0% compared to 17.4% for placebo.
  • At six months, the relapse rate in the probiotic group was 8.7% compared to 26.1% in the placebo group.
  • At 9 months, the relapse rate in the probiotic group was 21.7% compared to 34.8% in the placebo group.
  • At 12 months, the remission rate was 30.5 % in the probiotic group and 43.4% in the placebo group.
  • Fecal flora was analyzed and three clusters of bacterial profiles were identified: cluster I, cluster II, and cluster III. Cluster II has the highest levels of Bididobacteria and benefitted the least from the addition of the probiotic. Cluster I had the lowest level of Bifidobacteria and benefitted the most from the addition of the probiotic, which seems, among other things, to shift the flora to be more consistent with a cluster II bacterial profile. Cluster III was somewhere in the middle for Bifidobacteria.
  • The butyrate to acetate ratio was higher in patients who relapsed. The researchers suggest that the colonic cells are not able to uptake butyrate properly so it persists in the fecal matter.

Source: Yoshimatsu Y, Yamada A, Furukawa R, Sono K, Osamura A, Nakamura K, Aoki H, Tsuda Y, Hosoe N, Takada N, Suzuki Y. Effectiveness of probiotic therapy for the prevention of relapse in patients with inactive ulcerative colitis. World J Gastroenterol. 2015; 21(19): 5985-5994.

[So why not just take Bifido? I think one has to think about the whole climate of the GI tract. Clostridium butyricum would not directly inoculate Bifido. I’d like to think it creates bacteriocins (its own natural antibiotics) and pH changes that can then allow Bifido to properly reproduce and thrive as indicated. Like bringing in hummingbirds by planting geraniums and butterfly bushes. I can put hummingbird food out in winter and bring them, but I haven’t really provided them an environment to prosper. It’s all about cultivating an environment for cure to effect itself–not about taking the magic pill for cure. That’s why food is key.]

Treating ulcerative colitis patients who had food allergies with Clostridium butyricum (420 mg twice daily, brand not mentioned) plus specific immunotherapy for a year reduced the need ulcerative colitis medication.

[Aside: If you have ulcerative colitis, has your healthcare professional suggested food allergy for your consideration?]

Eighty patients with food allergy (diagnosed by skin testing) associated ulcerative colitis were divided into four groups: placebo, Clostridium butyricum only, specific immunotherapy only (SIT), or Clostridium butyricum with specific immunotherapy together. Using Clostridium butyricum alone or specific immunotherapy alone non-significantly reduced the need for ulcerative colitis medication. However, using the treatments together significantly impacted and reduced the need for medication for ulcerative colitis.

The study also investigated the cellular differences and immune response differences among the placebo group, the food allergy ulcerative colitis group, and the non-food allergy ulcerative colitis group. There were marked, significant differences among the groups, reflecting the significance of food allergy on the cellular response of the body. This study found that food allergy associated ulcerative colitis has unique cellular and immune response differences. [It reinforced in my mind the need for inflammatory bowel patients to modify their diets, especially looking at the top 8 allergenic foods.]

Source: Specific immunotherapy plus Clostridium butyricum alleviates ulcerative colitis in patients with food allergy. Bin La. Fan Yan. Dong Lu. & Zhenlv Lin. Scientific Reports 6, Article number: 25587 (2016).

Taking Clostridium butyricum (Miya-BM, three tablets three times daily) after total proctocolectomy with ileal pouch anal anastomosis for ulcerative colitis seemed to decrease the risk of pouchitis compared to placebo over a two-year period.

Nine patients received the probiotic and eight patients received a placebo; however only seven of the probiotic patients completed the study. Only 1 of the probiotic recipients developed pouchitis, whereas 4 of the placebo patients did. The difference was not statistically significant. Miya-BM was the probiotic. It is the same strain and made by the same manufacturer as the Miyarisan Miyairi CBM 588 I mentioned in the last post. However, the label for the Miyarisan Miyairi CBM 588 tablets that I see have 270 mg compared to the 20 mg mentioned for this study. I’m not sure how to compare that for equivalent dosing among Clostridium butyricum probiotics.

As mentioned in the other studies above, Bifidobacteria increased with use of the Clostridium butyricum. (It also increased in the placebo arm, but the placebo was lactose, which the researchers feel may have allowed Bifidobacteria to increase.) It was also found that Escherichia coli also decreased with Clostridium butyricum use. One last interesting parameter to point out is the effect of Clostridium butyricum on AST and ALT values (“liver function tests”). Clostridium butyricum significantly reduced AST and ALT values compared to placebo.

Source: The effect of Clostridium butyricum MIYAIRI on the prevention of pouchitis and alteration of the microbiota profile in patients with ulcerative colitis. Yasueda, A., Mizushima, T., Nezu, R. et al. Surg Today (2016) 46: 939.

Irritable Bowel Syndrome (IBS)

Although Clostridium butyricum is commonly used in Asia for diverse indications, which I assume includes general symptoms of abdominal discomfort, bloating, and diarrhea (aka, irritable bowel syndrome), I did not readily find irritable bowel studies using Clostridium butyricum. I’ll present what I did find.

A new 2018 study on mice concluded that Clostridium butyricum may exert a beneficial action on visceral hypersensitivity of IBS by inhibiting low grade inflammation of colonic mucous through its action on NLRP6.

NLRP6 is thought to help stabilize the intestinal epithelium to allow repair. In this mouse study, Clostridium butyricum (dose: 1.25×10^9 CFU once daily for 7 days) increased NLRP6 while inflammatory IL-18 and IL-1B were decreased. Inflammatory infiltration into the colonic mucosa was decreased in the mice who received the probiotic. Mice who received Clostridium butyricum had less visceral sensitivity.

Source: Kejia Zhao, Leimin Yu, Xi Wang, Yibo He, Bin Lu; Clostridium butyricum regulates visceral hypersensitivity of irritable bowel syndrome by inhibiting colonic mucous low grade inflammation through its action on NLRP6, Acta Biochimica et Biophysica Sinica, Volume 50, Issue 2, 1 February 2018, Pages 216–223.

In a 2013 Chinese study, two groups of irritable bowel patients received the same dietary information and were maintained on common drug treatments. However, in addition, one group received Clostridium butyricum 500 mg twice a day for a month. At the end of the month, the researchers reported a significant improvement in symptoms of the Clostridium butyricum group.

The study is a Chinese study, and I cannot find it any more than I reference.

Source: http://en.cnki.com.cn/Article_en/CJFDTOTAL-GLYZ201303005.htm.
Zhu Ya-bi, Li Hong-guang, Wang Chang-xiong, Wang Wang-yue. Effects of clostridium butyricum in adjuvant treatment of patients with irritable bowel syndrome. The Chinese Journal of Pharmacology. 2013.

To prevent antibiotic associated diarrhea

In children who required antibiotics, Clostridium butyricum (MIYAIRI) decreased the frequency of antibiotic-associated diarrhea. The probiotic was effective in both prophylactic prevention of diarrhea and also in treatment of antibiotic-associated diarrhea.

Study participants were divided into three groups: antibiotic only, antibiotic with Clostridium butyricum started half-way through the duration of antibiotic, and antibiotic with Clostridium butyricum given at the start of antibiotic dosing. The dose of Clostridium butyricum CBM was 1-4 grams daily of 10^7 CFUs in the form of a dissolvable powder. When the dose was higher than 3 grams, the beneficial effect of the Clostridium butyricum on loose stools was statistically significant: 83% versus 49%. Stool studies also showed that a more normal microbial flora was preserved with concomitant use of the probiotic.

Source: SEKI, H., SHIOHARA, M., MATSUMURA, T., MIYAGAWA, N., TANAKA, M., KOMIYAMA, A. and KURATA, S. (2003), Prevention of antibiotic-associated diarrhea in children by Clostridium butyricum MIYAIRI. Pediatrics International, 45: 86–90.

In a small study of 19 patients being treated for Helicobacter pylori with amoxicillin and clarithromycin, Clostridium butyricum (Miyairi CBM 588) at increasing doses eliminated diarrhea and/or soft stools. (A “regular” dose of 6 tablets of 10^7 CFUs showed a decrease in diarrhea, but a double dose of 12 tablets seemed to prevent diarrhea completely.)

Source: Efficacy of Clostridium butyricum preparation concomitantly with Helicobacter pylori eradication therapy in relation to changes in the intestinal microbiota. Kyoto Imase, Motomichi Takahashi, Akifumi Tanaka, Kengo Tokunaga, Hajime Sugano, Mamoru Tanaka, Hitoshi Ishida, Shigeru Kamiya and Shin’ichi Takahashi. Microbiology and Immunology. Volume 52, Issue 3, Version of Record online: 8 APR 2008.

Closing

I’ll have more coming on leaky gut, anxiety, pathogenic gut infections, and more!

Terri