Saccharomyces boulardii improves migration of new epithelial cells

The lifespan of healthy intestinal epithelia is generally accepted to be about 5 days.  These cells, once departed and sloughed off into the fecal stream, are replaced by newer, younger, healthier cells which proceed through the same life-cycle.  In the case of inflammatory bowel diseases (IBDs), in addition to inflammation/ulceration/tissue injury, the migration process of these new epithelial cells is stunted.  Since the replacement cells have trouble reaching their destination, damage to the intestinal lining is exacerbated.

A recent study -- published in PLoS ONE and open access if anyone wants to take a peek -- investigated the capacity of a nonpathogenic yeast to alleviate this stunted migration of new epithelial cells to the tips of intestinal villi (the fingers of tissue that protrude from the intestinal wall to create surface area for absorption).  Saccharomyces boulardii (Sb) is typically used to treat issues such as diarrhea, the idea being that it stimulates growth factors that help restore homeostasis to the gut.

This nigh-rockstar study strikes me because it is targeting a curative mechanism as opposed to a squelching of symptoms.  To achieve actual remission in IBDs, one has to pwn both inflammatory and repair dysfunctions.  The inflammatory component is predominantly targeted by the entourage of immuno-suppressants with which Crohns are so familiar.  Repair is seldom highlighted as it should be -- excepting methods of balancing gut flora.

The team of scientists in France, lead by one Frederic Andre, looked at the beneficial effects of Sb in both mice and an in vitro wound model (this is a strain of cultured epithelial cells which are attacked gently with a toothpick... rather cute).

The first major finding was that mice who were fed Sb for one week doubled new epithelial cell migration.  Only one downer for me in this study was that the mice were all healthy, with no in vivo IBD model for comparison.  Nonetheless quite encouraging, no?

The second conclusion was that the wounded cell line closed its wound (or, repaired its injury) by roughly 70%.  Their video supplement to this end is quite something.

The scientists conclude that Sb improves new epithelial migration both in vivo and in vitro.  Interestingly, the study suggests that increased migration is due to increased motility of cells and not to increased proliferation (the generation of new cells).  Sb may be stimulating this activity by secreting factors that stimulate  a target signaling pathway FAX/paxillin, which leads to several physiological changes in the intestinal epithelial lining that enable motility of new epithelial cells.

The thing about supplement studies such as this one is that they make me want to stop by the grocery and pick some up on my way home...


Canonici A, Siret C, Pellegrino E, Pontier-Bres R, Pouyet L, Montero MP, Colin C, Czerucka D, Rigot V, & André F (2011). Saccharomyces boulardii Improves Intestinal Cell Restitution through Activation of the α2β1 Integrin Collagen Receptor. PloS one, 6 (3) PMID: 21483797

in indirect support of the hygiene hypothesis

A recent study out of the University of Michigan Medical School suggests that the stomach bacterium Helicobacter pylori protects against inflammation caused by Salmonella in a mouse model of Inflammatory Bowel Disease (IBD).

This is surprising for two reasons: 1) IBDs occur primarily in the colon while H. pylori is active in the stomach, and 2) the H. pylori bacterium is regarded as dangerous gut flora and typically treated with antibiotics to avoid the development of stomach ulcers.

The findings of Higgins et al are equally unsurprising given the light that has been shed on helpful bacterial/parasitic gut balance by the Hygiene Hypothesis.  The Hygiene Hypothesis suggests that a modest intestinal hookworm population may stave off the excessive inflammatory response inherent to Crohn's disease, Lyme disease, asthma, rheumatoid arthritis and other conditions.  If this parasite whose reputation is built from its roles in epidemic illnesses in countries where sanitation is poor can, in small doses, help defend inflammatory diseases, then why couldn't the H. pylori bacterium as well?

There are currently no reports of an additive or destructive effect of both H. pylori and hookworm on gastrointestinal inflammation in humans, although it would be quite telling to see the results of their coincidence.  Patients from many H. pylori studies have been excluded from reports because they also shown signs of hookworm-related anemia (Vijayan et al 2007, as an example).  But this scientists wonders, because humans evolved almost symbiotically with both of these flora, if all of our immune systems would be better balanced were we not to wipe them both out completely.

A few thoughts from Dr. Higgins, one of the Salmonella study's researchers, can be found in an interview here.


Higgins PD, Johnson LA, Luther J, Zhang M, Sauder KL, Blanco LP, & Kao JY (2010). Prior Helicobacter pylori infection ameliorates Salmonella typhimurium-induced colitis: Mucosal crosstalk between stomach and distal intestine. Inflammatory bowel diseases PMID: 20976712

an instance of misconstrued media reporting: placebos

A most recent example of the media mis-representing scientific findings is the recent NPR report on placebos being equally effective in IBS patients as "the strongest prescription drugs", even when the patients knew that they were being given the placebo.  This coverage was a translation of a study out of Harvard Medical, and published in PLoS ONE.


The study, termed "honest placebo", didn't actually eliminate the deception for which placebo studies are renowned.  In the methodology, the researchers report telling the patients who received placebo treatment that “placebo pills, something like sugar pills, have been shown in rigorous clinical testing to produce significant mind-body self-healing processes.”  By this design, the patients may have received a similar benefit to what they would have experienced if they had expected that they were being given a strong prescription drug.  The patients were given the impression that the placebo would help them.  What would have contributed even greater meaning to this study is an additional group who were told that they were receiving a placebo drug, but not told that it was expected to help them.


As many of the comments on the NPR report echo, a strong component in placebo studies is the idea of holism and self-healing.  Dr. Ted Kaptchuk, a co-investigator in the Harvard study, states in his interview that the healing factor was assumed to be the "self-healing ritual" of dosing oneself twice daily, even with a placebo.  This scientist would suggest that self-healing is as likely to take place due to the belief that a placebo had been reported helpful as it is to be due to the ritual of pill-taking.


The great value of this study's conclusions is lost in the media translation: there is healing potential in having the expectation that your therapy will work. 
 NPR does the courtesy of acknowledging that "placebos don't shrink tumors or stop multiple sclerosis in its tracks".  However, particularly for conditions such as IBS, which have consistently shown to be negatively effected by stress and proactive treatment, this study's findings are important to treatment development.


Ted J. Kaptchuk, Elizabeth Friedlander, John M. Kelley, M. Norma Sanchez, Efi Kokkotou, Joyce P. Singer, Magda Kowalczykowski, Franklin G. Miller, Irving Kirsch, Anthony J. Lembo (2010). Placebos without Deception: A Randomized Controlled Trial in Irritable Bowel Syndrome PLoS