Tag Archives: increase butyrate

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

12 Replies

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.

Butyrate Series, Part 8

33 Replies

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 butyricum: https://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.