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

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 JNeurosci 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

 

 

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

  1. Tim Steele

    You’ve created a nice resource for C. butyricum and butyrate here, thank you. There are definitely lots of studies on C. butyricum probiotic benefits. It makes me wonder, are all these studies designed to monetize C. butyricum? Are food sources better? Where do we get C. butyricum? I looked back through my library of gut tests, and see C. butyricum was found in several reports, and “Clostridium” was found in every report, so I assume that C. butyricum is a normal gut bacteria. Perhaps one day we’ll have this all dialed-in and doctors will test for this specific bacteria, or perhaps we should start eating more foods that contain this particular species (and eat some dirt now and then, lol). Wikipedia says: “C. butyricum is a soil inhabitant in various parts of the world, has been cultured from the stool of healthy children and adults, and is common in soured milk and cheeses.”

    Hope you are surviving winter, almost over!

    Reply
    1. thehomeschoolingdoctor Post author

      Yes, I do think there is a component of monetizing it in some of these studies.

      Where did you see the C. butyricum species on your reports? Was it on uBiome? Under the expandable taxonomy tree?

      It is a normal gut bacteria for some people. (And I think it’s found on potatoes too.) I waver on taking/giving probiotics because my personal experience doesn’t have any significant gains, but the research is commonly so good! Real food, lots of plant-matter, though, and I definitely notice a difference.

      We are surviving winter, even thriving winter! It is almost ready to concede to the sun and warmer air!

      Reply
      1. Tim Steele

        To see species from uBiome, you have to further analyze the raw data with a 3rd party analysis such as MG-Rast (http://www.mg-rast.org/). UBiome only shows down to genus level, but their raw data is quite capable of predicting species.

        If you want to try to analyze a sample, I wrote about it here: http://vegetablepharm.blogspot.com/2015/09/ubiome-data-analysis-using-mg-rast.html

        It’s quite possible that clinical trials on probiotics show such great results because of other factors besides these bacteria living within a gut flora. When you swallow megadoses of bacteria, it certainly has an effect on the immune system. Perhaps some of these probiotic bacteria have a better effect than others. But, we must remember, the only reason there are commercially available probiotics is because all of the bacteria used have some other food/industrial use and the FDA has allowed them to be used as dietary supplements. That’s why there are no probiotics containing the multitude of other studied bacteria, ie. Roseburia, Akkermansia, etc…. Once there are probiotics that can replenish actual human gut flora, then we will probably start to see some real advances in the field, but will definitely require testing and professional oversight.

      2. thehomeschoolingdoctor Post author

        Thanks. That’s a wonderfully technical post. Will have to actually think to read and understand it and the comments. I’m kind of qualitative brained , so a bit tougher.

        Guess we’ll wait and see if all this gut stuff goes anywhere or not medically. I have a sister in med school who is going to do FMT research this summer. So I’m kind of excited for her to share what she learns with me.

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