Tag Archives: dairy allergy

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



Cow’s Milk and Refractory Constipation

Dripped homemade yogurt

Dripped homemade yogurt

Here below, I’ve listed some medical articles that I have read in the last six months regarding chronic constipation and dairy’s potential role in its causation.  No physician, in a professional relationship or friend relationship, ever mentioned to me or my husband that dairy could be causing my daughter’s chronic constipation that required daily Miralax for years.  I just don’t think they knew that constipation could be a nearly sole symptom of milk-intolerance.  I didn’t.  I do now, and so do they  (they’ve been texted, e-mailed, called, and “Christmas card updated”).

As dairy elimination did not take care of my issue with the same problem, I was relieved to find some journal articles on multiple food intolerances leading to chronic constipation.  I am doing this thing called the GAPS diet for my gut, I don’t know if it is working as a “whole regimen” or if going through the diet has allowed me to identify problematic foods.  Regardless, things are better for myself and my daughter, and I am glad I found these articles helping me to look beyond dairy as constipation triggers.  Laxatives were not working for me so well, and I was getting worried.

As I will and must say, it is ever important to make sure that there’s no serious disorder that needs to be evaluated–like cancer, inflammatory bowel disease, or another bad illness.  I’ve seen my doctors, and so must you make sure that nothing is being missed in your own body.  Also, I would like to point out that, although many of these articles are regarding children, my constipation started in early childhood–so I translated the studies to myself and adult studies seem to support this.

  • Chronic constipation and food intolerance: a model of proctitis causing constipation.Carroccio A, Scalici C, Maresi E, Di Prima L, Cavataio F, Noto D, Porcasi R, Averna MR, Iacono G.  Scand J Gastroenterol 2005 Jan; 40(1):33-42.
    A pediatric study finding cow’s milk intolerance manifesting as constipation in 24/52 patients.  Actual pathologic changes were found in the rectal mucosal biopsies of these affected patients, as well as decreased rectal mucus-gel layer.
    (Proctitis is basically the inflammation of the anus and lower rectum, resulting in clinical symptoms of cramping, feeling like you still have to have a bowel movement even after you’ve had one, painful defecation, anal irritation/itching, and pus or blood in bowel movement.  It can be caused by many things, but in this study, they found that dairy intolerant kids had it.)
  • Multiple food hypersensitivity as a cause of refractory chronic constipation in adults.  ANTONIO CARROCCIO, LIDIA DI PRIMA, GIUSEPPE IACONO, ADA M. FLORENA, FRANCESCO D’ARPA, CARMELO SCIUME` , ANGELO B. CEFALU`, DAVIDE NOTO & MAURIZIO R. AVERNA.  Scandinavian Journal of Gastroenterology, 2006; 41: 498/504.   A very small sample of four women was found to have severe, refractory constipation alleviated by initiation of an oligo-antigenic diet (hypoallergenic diet–put simply, the women were put on a limited diet of foods that most people are not allergic to).  Elimination diet eventually allowed each patient to pinpoint multiple food intolerances causing their constipation.  Researchers also found pathologic changes in the rectum, duodenum, and esophagus of the patients as well.

  • Intolerance of Cow’s Milk and Chronic Constipation in Children  Giuseppe Iacono, M.D., Francesca Cavataio, M.D., Giuseppe Montalto, M.D., Ada Florena, M.D., Mario Tumminello, M.D., Maurizio Soresi, M.D., Alberto Notarbartolo, M.D., and Antonio Carroccio, M.D.  N Engl J Med 1998;  339:1100-1104October 15, 1998DOI:  10.1056/NEJM199810153391602.  One of the first larger studies to support milk causing childhood chronic constipation.  Also read the interesting editorials that both try to refute and support the findings.  I believe the first criticism may be concerned about the implications of removing a nutrition-packed food source from children’s diets, especially very young children.

  • Functional constipation in children: does maternal personality matter?  Alireza Farnam, Mandana Rafeey, Sara Farhang* and Saeedeh KhodjastejafariItalian.  Journal of Pediatrics2009, 35:25 doi:10.1186/1824-7288-35    As  my daughter quickly responded to dairy removal, I found this research article quite comical  (but I’m secretly relieved that dairy elimination and low nut intake keeps her regular!  Laugh!).

  • Constipation in childrenNadeem A Afzal1*, Mark P Tighe2 and Mike A Thomson3  Italian Journal of Pediatrics 2011, 37:28 doi:10.1186/1824-7288-37-28.
    A review article in general about childhood constipation.  A brief blurb in there about cow-milk deserving a trial if there’s a family history of cow-milk intolerance, etc.  However, in our family, prior to May, we were completely unaware of “milk-intolerance” presence in our family, as I just did not know that sinusitis, chronic cough, and constipation could be related to dairy intolerance.

  • World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow’s Milk Allergy (DRACMA) Guidelines.  Alessandro Fiocchi, (Chair), Jan Brozek, Holger Schu¨nemann, (Chair), Sami L. Bahna, Andrea von Berg, Kirsten Beyer, Martin Bozzola, Julia Bradsher, Enrico Compalati, Motohiro Ebisawa, Maria Antonieta Guzman, Haiqi Li, Ralf G. Heine, Paul Keith, Gideon Lack, Massimo Landi, Alberto Martelli, Fabienne Rancé, Hugh Sampson, Airton Stein, Luigi Terracciano, and Stefan Vieths.  WAO Journal.  2010.  57-161.  A huge review article.  But buried in there are segments on constipation and dairy.  Also other good information.

If you’re reading this to help yourself or your child, best wishes to you on your endeavors, and I hope you find clues to better GI health soon!
Update:  I have come back through to edit this post a little.  Our constipation has improved significantly with the removal of all dairy products.  We even tried goat’s milk, but we failed the trial.  My daughter occasionally gets ice cream or a cake with some dairy in it at a birthday party or on vacation, and we have noticed that although she may skip a couple of days, her GI tract gets moving again without any Miralax.  Definitely an improvement!
Other constipation posts: