Tag Archives: increased intestinal permeability

More Butyrate Series, Part 8: Clostridium butyricum for the Brain, for Colon and Bladder Cancer, and for Milk Allergy

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I hate disclaimers. I don’t feel like they should be necessary on an internet site, where people should be reluctant to believe anybody or anything. But, sometimes we’re gullible and vulnerable, especially when it comes to our health. So I just want to remind readers that I am not recommending Clostridium butyricum. I am not speaking against it either.  What you put in your mouth is as personal as who you let French kiss you. Have caution.  I do.

Do I think Clostridium butyricum sounds like a decent probiotic? On paper it does. But I’m aware that each person’s gut is unique beyond comprehension. Its function is as varied as each person’s diet, stress level, and sleep pattern. That’s pretty varied. Please never go out and buy or use a supplement because I mention it. I’d feel just horrible about that. Read the studies I reference. Read the internet anecdotes for the good AND THE BAD. Then, talk with your doctor about if he or she sees any harm for you based on what he or she knows about you.

Try hard to make your diet as real and whole as you realistically can. That’s a great start for health! And also try hard to savor each person you love in your life. Our life on Earth really is unpredictable, and each moment counts. For more on Clostridium butyricum on my site, read here, here, and here.  I’ve enjoyed searching for information about it and putting it in one “place.” I hope if you’re reading this far, you find what you’re searching for. If you can’t understand something, please ask.

Clostridium butyricum For Vascular Dementia

In a vascular model of disease, mice with carotid artery occlusion who were given Clostridium butyricum (strain WZMC1016 dosed at 5 x 10 ^6, 5 x 10^7, 5 X 10^8) had improved cognitive test scores.

In humans, this might translate into someone who has vascular dementia from atherosclerosis—“clogged arteries.” The probiotic-treated mice fared significantly better on motor skills testing and cognitive skills testing (numerically significant at the two higher doses). Their brains looked better in the hippocampal region, a region known to be exceptionally sensitive to low blood flow, than the non-treated vascular occlusion subjects. Please notice that dose did affect the outcome!

The specifics, if you’re interested, also indicated that the probiotic treated mice had:

  • Increased levels of BDNF (brain-derived neurotrophic factor)
  • Increased ratio of Bcl-2 to BAX (antiapoptotic to proapoptotic factors)  (10^7, 10^8 doses)
  • Increased ratio of p-Akt/Akt (Akt phosphorylation=p-Akt) (5×10^7, 5×10^8 doses)
  • Structural preservation of the hippocampus with reduced apoptosis of neurons in the hippocampus (dose of 5 x 10^8)
  • Increased butyrate in the feces
  • Increased butyrate in the brain (10^7, 10^8 doses)
  • Increased diversity of GI bacteria (“drastically changed” were the words) (10^7, 10^8 doses).

Source: Liu J, Sun J, Wang F, et al. Neuroprotective Effects of Clostridium butyricum against Vascular Dementia in Mice via Metabolic Butyrate. BioMed Research International. 2015;2015:412946. doi:10.1155/2015/412946.

Clostridium butyricum for Stroke

In a mouse study which simulated cerebral ischemia/reperfusion injuries, such as those which may be found in a stroke in humans, mice who were pretreated with Clostridium butyricum (strain WZMC1018 at 1 x 10^9 dose) had less neurological deficits than the other mice.

In addition, in the probiotic treated mice it was found that:

  • The expression of Caspase-3 and Bax were significantly decreased
  • The Bcl-2/Bax ratio was significantly increased
  • Butyrate content in the brain was significantly increased
  • Apoptosis in the hippocampus was ameliorated
  • Decreased contents of MDA; increased SOD in the brain tissue.

Source: Clostridium butyricum pretreatment attenuates cerebral ischemia/reperfusion injury in mice via anti-oxidation and anti-apoptosis.Sun J, Ling Z, Wang F, Chen W, Li H, Jin J, Zhang H, Pang M, Yu J, Liu J. Neurosci Lett. 2016 Feb 2;613:30-5. doi: 10.1016/j.neulet.2015.12.047. Epub 2015 Dec 28.

Clostridium butyricum in Traumatic Brain Injury

In a traumatic brain injury model, Clostridium butyricum administration in mice resulted in improved outcomes.

Specifically found were:

  • Improved neurological deficits
  • Decreased brain edema
  • Less impairment in the blood brain barrier
  • Increased GLP-1 production in colon and increased GLP-1 receptor protein expression in the brain  (GLP-1 is glucagon-like peptide-1 and is considered a mediator between the gut and the brain.)
  • An improved intestinal barrier, evidenced by decreased serum D-lactate levels.

Source: Neurogastroenterol Motil. 2017 Nov 27. doi: 10.1111/nmo.13260. [Epub ahead of print]Clostridium butyricum exerts a neuroprotective effect in a mouse model of traumatic brain injury via the gut-brain axis.Li H, Sun J, Du J, Wang F, Fang R, Yu C, Xiong J, Chen W, Lu Z, Liu J.

Clostridium butyricum for Prevention of Anxiety

Laryngeal cancer patients who required surgery (laryngectomy) had lower anxiety parameters when they received Clostridium butyricum before surgery.

Human laryngeal cancer patients received Clostridium butyricum (420 mg/capsule, two capsules twice a day) prior to surgery for about 14 days. When compared to placebo-receiving laryngeal cancer surgical patients, they had:

  • Lower corticotropin-releasing factor levels (CRF), a stress-related hormone, also commonly known as corticotropin-releasing hormone (CRH)
  • Lower morning and evening heart rates
  • Lower anxiety test scores.

Source: Yang, Hui & Zhao, Xiaoyun & Tang, Shan & Huang, Hua & Zhao, Xiulan & Ning, Zhuohui & Fu, Xiurong & Zhang, Caihong. (2014). Probiotics reduce psychological stress in patients before laryngeal cancer surgery. Asia-Pacific journal of clinical oncology. 12. 10.1111/ajco.12120.

Clostridium butyricum for Bladder Cancer and Colon Cancer

The association of Clostridia affecting cancer goes back to 1813, when it was noted that patients who acquired gas gangrene (Clostridium perfringens infection) had cancer regression! Because they are anaerobic organisms, they emerge from spore form to vegetative form in the anaerobic, necrotic centers of tumors, where the bacteria can promote tumor destruction. (1)

An in vitro and in vivo mouse study showed that Clostridium butyricum induced bladder cancer tumor cell death (apoptosis). 

Rather than oral administration, Clostridium butyricum (both in the in vitro and in vivo arms) was directly applied to the tumor cells. The study found the administration:

  • Increased TRAIL (tumor necrosis factor-related apoptosis-inducing ligand ) release from polymorphonuclear leukocytes (PMNs), perhaps more effectively and safely than the current therapy, BCG
  • Drastically suppressed growth of bladder cancer cells in vitro and in vivo.

Sources: (1) Mowday AM, Guise CP, Ackerley DF, et al. Advancing Clostridia to Clinical Trial: Past Lessons and Recent Progress. Dachs G, ed. Cancers. 2016;8(7):63. doi:10.3390/cancers8070063.

(2) Clostridium butyricum MIYAIRI 588 shows antitumor effects by enhancing the release of TRAIL from neutrophils through MMP-8. Masahide Shinnoh and Mano Horinaka et al. Journal of Oncology. March 2013. Volume 42 Issue 3. pp 903-911.

In a colon cancer model study, researchers found that Bacillus subtilis and Clostridium butyricum inhibited proliferation of colorectal cancer cells and promoted cancer cell apoptosis in vitro and in vivo.

Mice with induced colon cancer were used for the in vivo study, and human colon cancer cells used for the in vitro study. The researchers noted improved inflammatory markers and immune responses.

  • TLR4 mRNA was decreased with the probiotic administration.
  • NfKb was also decreased with the administration of the probiotics.
  • The probiotic treated cancer-model mice had downregulation of Th17 cells as compared to the non-treated cancer mice.

Source: Chen ZF, Ai LY, Wang JL, Ren LL, Yu YN, Xu J, Chen HY, Yu J, Li M, Qin WX, et al. Probiotics Clostridium butyricum and Bacillus subtilis ameliorate intestinal tumorigenesis. Future Microbiol. 2015;10:1433–1445. doi: 10.2217/fmb.15.66.

Clostridium butyricum to reduce food allergy (milk allergy)

Clostridium butyricum reduced intestinal anaphylaxis to beta-lactoglobulin in mice with induced allergy and the researchers felt the probiotic might have potential as a  supplemental therapy for food allergy.

Mice who had a milk allergy to beta-lactoglobulin were given Clostridium butyricum. When given the probiotic, the treated mice, as compared to the untreated mice, had:

  • Decreased diarrhea
  • Improved villus histological integrity with decreased amount of inflammatory cells [It really was pretty cool if you like histology.]
  • Increased CD4+ CD25+ Foxp3+ Treg cells in the MLN and high levels of TGF-β and IL-10 in the serum
  • High levels of TGF-β and IL-10 in the serum
  • Reversed imbalance of Th1/Th2 andTh17/Treg.

Source: Zhang J, Su H, Li Q, et al. Oral administration of Clostridium butyricum CGMCC0313-1 inhibits β-lactoglobulin-induced intestinal anaphylaxis in a mouse model of food allergy. Gut Pathogens. 2017;9:11. doi:10.1186/s13099-017-0160-6.

Closing and Personal Anecdote

I think that’s all the studies I’ll go through on Clostridium butyricum for a while. My eyes were kind of drooping near the end. Make sure and comment on typos or wrong information so I can address them!

I did try this probiotic several times off and on over the last couple of years at all kinds of doses. I had no major issues from it when I took it, but I did have some minor ones. (But my gut is not your gut.) Despite this probiotic reportedly being used for constipation in Asia, I found that my baseline constipation increased and I had to increase my magnesium laxative use while taking it. I also experienced bloating. I had a good sense of well-being on the probiotic, but I have a tendency to have that much of the time anyhow. I seemed to wake up earlier, but I think that could be anything. Due to the constipation and (painless but pretty significant) bloating, I could never extend my use of this probiotic more than two weeks. I didn’t know if it was the probiotic itself or the lactose in it.

That’s it for today.

Terri F

 

 

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.