Diarrhea word cloud concept

Long-time readers of this blog know that my main emphasis has been on gut bacteria and the substrates those bacteria utilize to grow and thrive. Apart from scattered mention of other organisms like Candida albicans (a yeast we all harbor), fungi have never been a focus of my musings. I thought now was a good time to make an exception to that rule.

Sacchoromyces boulardii (S. boulardii) is a probiotic yeast. S. boulardii is a curious probiotic because unlike microbes found in the Lactobacillus and Bifidobacterium families, or a native yeast like Candida, it isn’t a normal constituent of the human gut. In fact, while detectable levels are quite easily discovered in stool while taking probiotics containing S. boulardii, it’s rapidly cleared from the gut a few days after discontinuing use. (1)

So why bother taking it at all? Because a number of animal and human studies have shown it to have a remarkable ability in reducing or stopping diarrhea precipitated by known or unknown causes.

Following are several excerpts from some of these studies:

The objective of the present report is to provide an update on the evidence for the efficacy of S. boulardii CNCM I-745 in different clinical conditions. Saccharomyces boulardii is one of the best-studied probiotics in acute gastroenteritis (AGE) and is shown to be safe and to reduce the duration of diarrhea and hospitalization by about 1 day. Saccharomyces boulardii is one of the recommended probiotics for AGE in children by European Society of Paediatric Infectious Diseases and European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN). Saccharomyces boulardii is also a recommended probiotic for the prevention of antibiotic-associated diarrhea (AAD), and a recent study showed promising results for the treatment of AAD in children...Saccharomyces boulardii could be used in patients needing Helicobacter pylori eradication because the S. boulardii improves compliance, decreases the side effects and moderately increases the eradication rate. There are new promising results (improving feeding tolerance, shorten the course of hyperbilirubinemia), but we do still not recommend the routine use of S. boulardii in newborns. (2)

A 2009 review of S. boulardii for the treatment of Clostridium difficile infection (CDI) found:

The present review of four trials suggests that there may be some benefit in using S. boulardii for treatment and secondary prevention in patients experiencing recurrent CDI in conjunction with a particular concurrent antibiotic treatment. Because only a small number of studies address the primary prevention of CDI, more research is required before any changes in practice can be recommended with regard to using S. boulardii prophylactically. The risks of administering S. boulardii seem to be minimal compared with placebo, but because of case reports of potential morbidity secondary to serious fungemia, the use of this yeast agent should be considered on a case-by-case basis. (3)

From a 2010 meta-analysis:

This article reviews the evidence for efficacy and safety of Saccharomyces boulardii (S. boulardii) for various disease indications in adults based on the peer-reviewed, randomized clinical trials and pre-clinical studies from the published medical literature (Medline, Clinical Trial websites and meeting abstracts) between 1976 and 2009…S. boulardii was found to be significantly efficacious and safe in 84% of those treatment arms. A meta-analysis found a significant therapeutic efficacy for S. boulardii in the prevention of antibiotic-associated diarrhea (AAD) (RR = 0.47, 95% CI: 0.35-0.63, P < 0.001). In adults, S. boulardii can be strongly recommended for the prevention of AAD and the [sic] traveler’s diarrhea. Randomized trials also support the use of this yeast probiotic for prevention of enteral nutrition-related diarrhea and reduction of Helicobacter pylori treatment-related symptoms. S. boulardii shows promise for the prevention of C. difficile disease recurrences; treatment of irritable bowel syndrome, acute adult diarrhea, Crohn’s disease, giardiasis, human immunodeficiency virus-related diarrhea; but more supporting evidence is recommended for these indications. The use of S. boulardii as a therapeutic probiotic is evidence-based for both efficacy and safety for several types of diarrhea. (4)

A 2012 Indian study in children suffering from diarrhea found:

Children aged between 3 mo and 59 mo with acute onset diarrhea (of less than 48 h) admitted in DTTU (diarrhea treatment and training unit) were included and those with clinical evidence of severe malnutrition, systemic infection, encephalopathy and/or convulsion, electrolyte imbalance, invasive diarrhea or previous use of any probiotics were excluded from the study. Those included randomly were given either a placebo or Saccharomyces boullardi (SB) in identical packets mixed with puffed rice powder.

Mean post intervention duration of diarrhea was significantly (95% CI = -28.13 to -5.43) shorter in SB group (52.08 ± 24.57 h) as compared to placebo group (64.04 ± 30.43 h). The time of appearance of first semi formed stool in SB group (39.48 ± 23.09 h) was significantly (95% CI -25.4 to -3.87) shorter than the placebo group (54.13 ± 28.21 h). No statistically significant difference was found in rest of the parameters. (5)

I could continue citing many more studies, but I think you get the point.

Now let me state for the record that the S. boulardii used in most of these clinical trials is freeze-dried (lyophilized) as opposed to heat-dried. So if you plan on using S. boulardii to treat gut dysbiosis, I highly recommend you seek out lyophilized S. boulardii.

This yeast is particularly helpful during antibiotic treatment. I’ve always recommended taking probiotics during such treatment to mitigate the inevitable damage to beneficial gut flora populations that ensues. Unfortunately, doing so requires some finesse as many antibiotics will kill probiotic organisms if taken within hours of each other. For that reason I advise taking microbial-based probiotics away from your antibiotic, preferably in the middle hour between doses.

There is no similar concern with regards to S. boulardii. As a yeast it is not affected by antibiotics so it can be taken concurrently with your medication.

The usefulness of supplementing with S. boulardii while on antibiotics is illustrated in the following graphic:

Courtesy: Saccharomyces boulardii CNCM i-745 supports regeneration of the intestinal microbiota after diarrheic dysbiosis. (X)

Courtesy: Saccharomyces boulardii CNCM i-745 supports regeneration of the intestinal microbiota after diarrheic dysbiosis. (6)

The blue line represents the dramatic decrease in gut flora populations seen during a typical two-week antibiotic course (red shaded area), and their slow recovery two weeks after treatment (green and white shaded areas).

The red line shows how ingesting S. boulardii while taking antibiotics can help protect beneficial gut flora, while the green line shows how S. boulardii can aid in regeneration if taken immediately after your last antibiotic course. The dotted line represents what would be expected to happen were S. boulardii to be taken both during and after antibiotic treatment.

Now as I said at the beginning, S. boulardii is not part of our native gut flora and is quickly cleared from of our guts once probiotics containing it cease to be taken. But that leaves us with a perplexing question.

Why would a yeast not native to the human gut help correct gut dysbiosis, especially in cases resulting in diarrhea, yet offer no benefit otherwise? Or to put it another way, what is it about this yeast that helps reestablish a healthy gut flora community?

Well, the closest analogy would be that S. boulardii acts much like a band-aid. Like a band-aid it’s not a normal part of the human body, but it nevertheless provides a temporary environment that is conducive to healing.

S. boulardii cell walls contain beta glucans (β-Glucans). These components are known to interact with certain intestinal immune cells, stimulating their action against pathogens like E. coli, Shigella or Yesinia. (7)

While increasing immune stimulation against gut pathogens, S. boulardii appears to simultaneously tamp down other inflammatory responses. (8) As I’ve often said before, recovery of healthy gut flora is often dependent on reducing the chronic inflammation that encourages and perpetuates pathogen replication.

Besides glucans, the cell walls of S. boulardii contain chitin and mannoproteins. All three components can be fermented by native gut flora to produce short-chain fatty acids, just like prebiotics. So S. boulardii also has prebiotic properties that would be expected to help seal a leaky gut and enhance gut-wall integrity through the production of butyrate. (9)

S. boulardii can produce and secrete polyamines. Polyamines are used by intestinal cells (enterocytes) for cell proliferation and differentiation. Polyamines also enhance the production of intestinal enzymes that inhibit the growth of pathogens. (10)

S. boulardii has been shown to release enzymes that attack C. difficile toxins. It’s also been shown to inactivate cholera and neutralize lipopolysaccharides derived from E. coli O55B5. (11) (12) (13)

It’s also been observed to act as a decoy binding a number of pathogens like Yersinia enterocolitica and Salmonella typhimurium thus preventing these organisms from adhering either to the mucus layer of the gut or burrowing their way to intestinal cells and disrupting tight-junctions between them. (14) Likewise, S. boulardii inhibits the growth of certain organisms including Candida albicans making it a useful treatment option for Candida overgrowth in the G.I. tract. (15)

Finally, S. boulardii is uniquely capable of filling niches in the gut that for whatever reason (use of antimicrobial drugs, infection, diet, alcohol, etc.) have become depleted of beneficial gut flora. Doing so prevents these sites from becoming colonized by opportunistic gut pathogens. But because it isn’t a natural commensal of the human gut, once beneficial bacteria repopulate these areas S. boulardii is displaced, and its band-aid or placeholder function comes to an end.

So for those of you out there battling diarrhea, or anticipate the same because of travel to a country with less than stellar food or water hygiene standards or as a result of taking antibiotics, I strongly recommend that you consider adding S. boulardii to your gut protective arsenal.

You may also want to consider taking it if you are fighting any type of gut dysbiosis whether or not it currently results in chronic diarrhea. While the evidence for its effectiveness in treating non-diarrheal gut dysbiosis is contradictory, I still consider it a helpful temporary adjunct to both prebiotic/probiotic supplementation and dietary modification.

The only exception I would make to this advice is in the case of a severe inflammatory disease of the gastrointestinal tract resulting in visible blood after defecation. Taking any probiotic containing live bacteria or yeast can lead to blood contamination if the gut wall is severely compromised. In those situations I highly recommend you consult with your physician prior to use to avoid any unnecessary medical complications.





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