Tag Archives: Clostridium butyricum

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

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. 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

Butyrate Series, Part 8

Hello! I have not stopped working on and constructing butyrate posts (or other posts, like recipes and homeschooling posts), but I haven’t been able to complete them in a very timely manner. Whew! Homeschooling is hard work! However, I’m ready to start posting the next installment of my Butyrate Series. Let’s look at another way to potentially increase butyrate production in the body. . .

Warning: Writing up what I’ve learned about certain topics is simply a hobby of mine. It’s my entertainment and way to unwind from motherhood, homeschooling, and housework. When you read my writing, I’d like you to enter into an agreement with me: you read it to see what I think I’ve learned, but you do not read it with the thought that I am some expert or that I can possibly help you. I can’t help you. Supplements and treatments discussed enthusiastically on the internet can be dangerous. You, however, armed with knowledge and curiosity, can take the initiative to safely and non-ignorantly make a difference for yourself. This site is not medical advice.

Probiotics to (directly) increase butyrate

The Japanese have used a strain of Clostridium butyricum, a direct butyrate-producing bacteria, as a probiotic since about the 1970s. Savvy health professionals know butyrate best for its gut benefits (healing leaky gut, improving the mucous barrier, and improving motility), but it also has positive effects on the kidneys, brain, and metabolism–not to mention colon cancer prevention. Despite its structural simplicity, the little short chain fatty acid called butyrate truly makes a powerful, all-encompassing health difference.

Personally, my favorite way to increase butyrate in the body is NOT to take supplements– but to eat green bananas, leftover boiled cassava root, and/or leftover potatoes. Aiming to eat whole, real food is always best, but it may not be enough for select problems.  I get that. So I’m curious about all the other ways to increase butyrate.

If you have read any of my butyrate posts, you may remember that I outlined and explored four potential ways to increase the body’s butyrate levels:

  1. Eat butyrate-rich foods, like butter from grass-fed cows.
  2. Eat foods that butyrate-producing bacteria like to metabolize, particularly green bananas, green plantains, refrigerated and then reheated potatoes, beans, lentils, cassava root, and/or rice.
  3. Take butyrate supplements directly.
  4. Take probiotics which contain bacteria known to make butyrate.

Since last writing, I’ve expanded my list of potential butyrate-producing methods that I’d maybe eventually like to write about:

5. Take probiotics which support butyrate-producing bacteria in the GI tract.
6.  Consume prebiotic fibers which enhance butyrate production by GI tract bacteria.
7. Maybe we could somehow upregulate our colonic butyrate importers, such as MCT1 and SMCT1. (1, 2)

My other butyrate posts have waded through points one through three. After quite a gap in my writing due to my work raising four wonderful people in the early stages of life, let’s talk about point number four: probiotics which contain bacteria known to directly make butyrate.

Commercially available butyrate-producing probiotics

The only direct butyrate-producing bacteria (that I found) that we have available as a probiotic for human consumption is Clostridium butyricum. Quite a bit of searching turned up only two different probiotic brands to buy with Clostridium butyricum. (Have you seen any others I’ve missed?) Although both probiotics contain spores of the same species, Clostridium butyricum, they are different strains of the species.

When ingested, the bacterial spores germinate and grow in the intestinal tract, making the short chain fatty acids butyrate and acetate (6). Both strains and brands have studies behind them for various health conditions which I’ll try to discuss in this thread of posts (but not in this post today). Both probiotics can be found on Amazon.

  1. MIYAIRI 588 (CBM 588) Miyarisan Tablets
  • A one-strain probiotic of Clostridium butyricum
  • Manufactured in Japan and distributed there as an over-the-counter medicine
  • Commonly available and used in Asia
  • Available in two strengths: standard and strong. If you look at my citation number 4, you’ll find the recommended dose and much, much more about this probiotic.
  • Other listed ingredients are lactose, corn starch, talc, microcrystalline cellulose, and magnesium stearate
  • History: First isolated from feces by Dr. Chikaji Miyairi in Japan in 1933. CBM 588 is the 588th MIYAIRI strain, isolated from a soil sample in Nagano, Japan in 1963.
  • As mentioned, the probiotic is composed of spores of C. butyricum (rather than “live,” active bacteria), which are then activated in the gastrointestinal tract, making the probiotic quite shelf stable with no refrigeration required. (3, 4)

2. Advanced Orthomolecular Research Probiotic-3

  • A three-strain probiotic which includes Clostridium butyricum TO-A, Enterococcus faecium (same as Streptococcus faecalis) T-110, and Bacillus subtilis TO-A (some places I see the label with Bacillus mesentericus)
  • Only the Clostridium butyricum is the direct butyrate-producing bacteria
  • Also contains lactose, potato starch, polyvinyl alcohol, providone, and sodium stearyl fumarate
  • If I understand correctly, it contains Bio-Three probiotic formula. I believe the “TO-A” implies that the strain was produced by the TOA Pharmaceutical company in Japan (inferred from Bio-Three website). The Bio-Three formulation is used in Japan, and has studies behind it.
  • No refrigeration necessary. As with the Miyairi probiotic, the Clostridium butyricum is in the shelf-stable spore form. (5)

About Clostridia and the bacterial species Clostridium butyricum in general

When we are about one month old, different commensal species of Clostridia start to colonize our gastrointestinal (GI) tracts. They are supposed to be there and provide specific and essential benefits to us without causing harm. Since we only typically hear of the toxic Clostridial diseases like botulism, tetanus, and “C. diff.,”  it may sound strange to some of you to know you healthfully have an abundance of clostridium residing in your GI tract! If you think of Clostridia as a “bad” class of bacteria, you might find it even more disturbing and confusing to know that a known pathogen like Clostridium difficile (the culprit in C. diff pseudomembranous colitis) can be part of a normal human gut biome or can actually prevent infection. (6-9)

[Opinionated aside: The fascinating idea that a strain of C. difficile, a bacteria we think of as toxic, can be normal flora supports why I would argue with people that we have to stop oversimplifying health, stop trying to peg things, and start convincing people to do complete overhauls to their modern lifestyles and mindsets to bring the body into rhythm with itself. Don’t just take butyrate supplements and butyrate-enhancing probioitics—investigate your life, eating, habits and make impact changes. Being honest with and scrutinizing oneself often hurts for several months, but if done properly, you move past the pain, and healing and change can begin. Perfection will never be reached in this realm, but progress feels so good to a mind and body.]

Clostridium butyricum is one species of Clostridia bacteria. It is Gram-positive, rod-shaped, and anaerobic. It lives in soil and in the GI tracts of birds and mammals and can be found on the skins of potatoes, Swedes, and even in cream and yoghurt. It ferments starches to produce butyrate. When C. butyricum is exposed to a stressful environment, it can form endospores, an alternative form which allows it to survive the stressful conditions, to later reactivate when exposed to desirable conditions. It is the spores which are used in the probiotic formulation, allowing them to be shelf-stable without refrigeration for several years. (3, 4)

Some of you may have read about the clusters of clostridia and wondered about that. The Clostridia microbiological class (to which C. butyricum belongs) is exceptionally diverse, and even the commonly accepted shared characteristics, such as being rod-shaped (bacillus), anaerobic, and spore forming, have variations and exceptions to the rules. In the attempt to break down, stratify, and classify the types of Clostridia, the species C. butyricum is categorized into what is called “Cluster I Clostridia.” Cluster I Clostridia aren’t common inhabitants of the human gut. Human guts seem to mostly contain butyrate-producing bacteria from Clostridium clusters IV and XIVa rather than cluster I, but some human GI tracts do contain Clostridium butyricum, so clearly it does naturally happen. Fecal studies have found Clostridium butyricum in about 10-20% of its surveys. (6-9)

For all practical purposes, C. butyricum is a non-toxic clostridium species, but there have been reports that it can acquire some of the toxic genes from other clostridia, leading to production of poisonous toxins which may contribute to infant botulism or infant necrotizing enterocolitis. Regarding adults, one case of sepsis from Clostridium butyricum has been reported in an intravenous drug user and one case of antibiotic associated diarrhea has been reported. The complexities of toxin acquisition/production depend on the strain, the host, and interactions with other strains. Some strains of Clostridium butyricum are probiotic and beneficial and other strains show virulence. The probiotic strains mentioned are tested for non-virulence.  (6, 7)

Closing

I’ll cut off this post for today and try to clean up my next writing segment regarding specific uses of the probiotic Clostridium butyricum. I do not have it “polished up” yet, but posting this half will force my hand to get the rest of it tidied up and posted for those interested. I’d like it if you’d point out typos or mis-information to me so I can make corrections. Thanks in advance.

Please keep in mind: I don’t really care about probiotics or bacteria or food. What I really care about is that you grasp your life, your whole life, and tenaciously latch on to the things that are good and real– and that you weed out the things that are bad for you and noxious. I love life. I’ve had my share of challenges, smaller than many, bigger than some. But no matter what, I try to choose to face life HEAD ON with as much transparency as I can. And each new day, each new week, each new stress, shows me how to become more true and real.

The best to you,

Terri F

Citations:

  1. Pedro Gancalves, Fa’tima Martel. Butyrate and Colorectal Cancer: The Role of Butyrate Transport. Current Drug Metabolism. Volume 14, Issue 9, 2013.
  2. Pedro Gonçalves, Fátima Martel. Regulation of colonic epithelial butyrate transport: Focus on colorectal cancer. Biomedical Journal. Volume 1, Issue 3, July–August 2016, Pages 83-91.
  3. Wikipedia site regarding Clostridium butyricumhttps://en.wikipedia.org/wiki/Clostridium_butyricum
  4. Clostridium butyricum Miyairi 588 Novel Food Application, public version: C. butyricum MIYAIRI 588 as a novel food supplement.  Probiotic food supplement. Miyarisan pharmaceutical company, LTD. https://acnfp.food.gov.uk/sites/default/files/mnt/drupal_data/sources/files/multimedia/pdfs/clostridiumbutyricumdossier.pdf
  5. Bio-Three website: http://www.bio-three.com/
  6. N.Cassir, S.Benamar, B.La Scola. Clostridium butyricum: from beneficial to a new emerging pathogen. Clinical Microbiology and Infection. Volume 22, Issue 1, January 2016, Pages 37-45. Review. 
  7. Rousseau, Clotilde & Poilane, Isabelle & De Pontual, Loic & Maherault, Anne-Claire & Le Monnier, Alban & Collignon, Anne. Clostridium difficile Carriage in Healthy Infants in the Community: A Potential Reservoir for Pathogenic Strains. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2012. 55. 1209-15.
  8. CS Cummins and JL Johnson. Taxonomy of the Clostridia : Wall Composition and DNA Homologies in Clostridium butyricum and Other Butyric Acid-producing Clostridia. Journal of General Microbiology.   (197 I), 67,33-46
  9. Lopetuso LR, Scaldaferri F, Petito V, Gasbarrini A. Commensal Clostridia: leading players in the maintenance of gut homeostasis. Gut Pathogens. 2013;5:23. doi:10.1186/1757-4749-5-23.