Before answering this question, let's first understand what yeast is. Yeast is a type of fungus that belongs to the kingdom Fungi. It is widely known for its use in baking and brewing, where it plays a crucial role in fermentation. Yeast has a long history intertwined with human civilization, yet many people are unaware of its origins.
The morphology of different yeast strains under the microscope
The emergence of yeast
The appearance of yeast can be traced back to around 2 million years ago, which is almost as long as the history of humans on Earth. One is a relatively primitive single-celled eukaryote, and the other is the most complex and advanced eukaryote on Earth. It is quite a miracle that yeast and humans have coexisted for so long without getting tired of each other.
The term "yeast" (Gist in Dutch) actually originates from the ancient Greek word "zestos," meaning "boiling." People at that time did not understand the underlying principles but discovered that using yeast to ferment sugars produced a large amount of foam, similar to boiling, hence the name yeast.
Yeast fermentation foam
Under the microscope, yeast appears similar to many bacteria as a round, single-celled organism. However, there is a fundamental difference between the two: yeast is a "eukaryotic" organism, whereas bacteria are "prokaryotic" organisms.
Yeast cells under a microscope at 1500x magnification
The term "eukaryotic organism" refers to organisms that have a "true nucleus," meaning all genetic information is stored in a separate, dedicated compartment. In contrast, bacteria do not have a nucleus; their DNA, along with other cellular components, resides in a single, large open space.
Having a nucleus means that genetic information is better protected, making it less likely for mutations to occur in the offspring. This explains why bacteria, which lack a nucleus, are more prone to genetic mutations during reproduction.
The use of yeast
Although yeast has a long history as a eukaryotic organism, humans only began to truly understand and utilize it in the mid-19th century, thanks to the discoveries of the French microbiologist Louis Pasteur. We owe thanks to Pasteur, as he was the first to link alcohol fermentation with yeast strains.
French microbiologist Louis Pasteur
It was later discovered that yeast is actually a "facultative anaerobe," meaning it can survive with or without oxygen. This is quite different from us humans, can you believe it? When oxygen is present, yeast performs aerobic respiration, but when oxygen levels are low or absent, yeast switches to anaerobic respiration.
Although both processes are forms of respiration, it is yeast's anaerobic respiration that humans find most useful. This process allows yeast to break down carbon sources (such as sugars and starches) to produce alcohol and carbon dioxide.
This capability is key to baking bread and brewing beer.
The relationship between yeast and humans is remarkably close. Many genes in yeast share high homology with human genes. Consequently, the study of yeast is indispensable in various fields, including genetic analysis of numerous important diseases and hereditary conditions in humans.
Moreover, yeast serves as a model organism in biological experiments to elucidate the functions of new genes. Many cutting-edge techniques in contemporary life sciences, such as cell autophagy, DNA damage, telomere shortening, and vesicle transport, rely heavily on yeast research.
Alright, now let's introduce today's main character: Saccharomyces boulardii.
Saccharomyces boulardii
Yeast is classified taxonomically under the subphylum Saccharomycotina, which belongs to the kingdom Fungi. Within the subphylum Saccharomycotina, yeast belongs to the family Saccharomycetaceae. The family Saccharomycetaceae is indeed diverse, comprising numerous genera and species. It is estimated that there are at least 1500 species (and subspecies) of yeast within this family.
That's right! Whether it's bread yeast, beer yeast, or even the yeast used in fermenting oolong tea in some regions, they all belong to the broad category of brewing yeast. Their functions in fermentation are quite well-known and widely understood.
Similar to other yeasts, today's protagonist, Saccharomyces boulardii, is also a subspecies of brewing yeast (although this is somewhat disputed). However, the story behind its discovery is intriguing, reminiscent of the discovery of Bacillus clausii's efficacy.
In 1920, French scientist Henri Boulard discovered serendipitously during his travels in India that consuming certain local teas could effectively prevent cholera infection—a significant concern during that era, far more severe than COVID-19. Driven by curiosity, he sought to unravel the mystery behind this observation and eventually isolated the renowned yeast strain—Saccharomyces boulardii.
As research into Saccharomyces boulardii deepened, its potential became increasingly apparent. For instance, a meta-analysis published as early as 2010 examined 53 randomized controlled clinical trials, involving nearly ten thousand children and adults. The results indicated that in 43 studies (81% of the total), Saccharomyces boulardii significantly improved various diseases while demonstrating high safety.
In the past two decades, Saccharomyces boulardii has not only gained recognition in academic circles but has also become quite popular in the probiotic product market in Europe and America. However, interestingly, its popularity in China is not as high as that of other probiotics like Lactobacillus and Bifidobacterium. This difference in popularity may be related to its unique character of not being a bacterium and thus not fitting in with the typical understanding of probiotics.
The mechanism of action and advantages of Saccharomyces boulardii
The following image vividly illustrates the various intestinal microbiota problems caused by different pathogens or antibiotics (on the left), as well as the several major roles played by Saccharomyces boulardii in the intestine.
The three major key functions
Firstly, Saccharomyces boulardii exhibits excellent toxin and pathogenic bacteria resistance, even against toxins from difficult-to-treat pathogens such as Clostridium difficile and cholera toxins. It can also reduce the invasion of pathogenic microorganisms into the intestinal mucosa.
Secondly, it can produce a large amount of beneficial metabolites, such as various amino acids and sugar alcohols. Many of these components are crucial substances for synthesizing B-complex vitamins. Among its metabolites, the most critical are short-chain fatty acids (SCFAs), such as acetic acid and butyric acid. These SCFAs not only facilitate the colonization of other beneficial bacteria in the gut but also thicken the intestinal mucosa, thereby protecting intestinal epithelial cells.
Clinical studies have shown that taking Saccharomyces boulardii can effectively repair intestinal permeability, protect intestinal mucosa, and maintain the stability of intestinal tight junctions.
Thirdly, it can increase the levels of antibodies such as IgA and IgG in the intestines, significantly reducing the levels of certain inflammatory signaling factors. This provides excellent assistance in cases of acute and chronic diarrhea caused by enteritis and other inflammatory conditions.
Three key advantages
Firstly, it harmonizes extremely well with the human body's internal environment. Saccharomyces boulardii not only exhibits strong acid resistance, ensuring its successful passage through the stomach to the intestines, but also its optimal "working" temperature is around 37 degrees Celsius, which coincides with the temperature of the human intestinal environment. This temperature is conducive to the production of short-chain fatty acids by Saccharomyces boulardii.
Secondly, there are no concerns about antibiotic resistance. Unlike other bacterial probiotics, Saccharomyces boulardii is a eukaryotic organism, so it does not acquire antibiotic-resistant genes and is not affected by antibiotics or other medications.
Thirdly, it shows rapid and non-colonizing effects. Similar to Bacillus clausii, Saccharomyces boulardii exhibits quick efficacy and does not colonize the intestine. After oral administration of Saccharomyces boulardii, noticeable effects can be seen within 3-7 days, and Saccharomyces boulardii is not detectable in the intestine 2-3 days after discontinuing its use.
Clinical efficacy
With such strong underlying mechanisms, it's natural that there is abundant clinical evidence for the efficacy of Saccharomyces boulardii in both adults and children. Currently confirmed diseases with significant therapeutic effects include inflammatory bowel disease (IBD), antibiotic-associated diarrhea (AAD), Clostridium difficile infection (CDI), acute adult/childhood diarrhea, leaky gut syndrome, irritable bowel syndrome (IBS), as well as adjunctive intervention for Helicobacter pylori infection, and more.
For various gastrointestinal diseases
For instance, in a study from 2010, researchers analyzed multiple clinical studies and found that Saccharomyces boulardii can accelerate the recovery time of patients with inflammatory bowel disease (IBD), reduce the recurrence of IBD, and improve the intestinal microbiota of IBD patients.
A meta-analysis has shown that Saccharomyces boulardii has therapeutic effects on both Crohn's disease and ulcerative colitis.
In several meta-analysis studies, consistent results have been observed showing that Saccharomyces boulardii can reduce the duration of acute gastroenteritis and diarrhea. For example, the results of 29 clinical trials (involving 3450 patients) and 5 randomized controlled trials (involving 619 patients) both indicate that taking Saccharomyces boulardii can reduce the duration of diarrhea by approximately one day.
Irritable bowel syndrome (IBS) is also a common and troublesome chronic gastrointestinal disease. Many individuals experience various symptoms of intestinal discomfort such as abdominal pain and diarrhea when they encounter stress or consume greasy or spicy foods.
Saccharomyces boulardii has shown good clinical efficacy in the intervention of IBS. For instance, a statistical analysis of 20 clinical trials involving the use of Saccharomyces boulardii in IBS patients found that it can improve various symptoms of IBS and reduce indicators such as abdominal pain and diarrhea.
Reducing the side effects of medication
In addition to addressing gastrointestinal issues such as gastroenteritis and diarrhea, Saccharomyces boulardii can improve the effects of medication on the intestines and reduce various drug resistances.
Because Saccharomyces boulardii is not affected by various medications, it can be used in conjunction with many anti-inflammatory or antibiotic drugs to effectively reduce adverse reactions, eliminate drug-resistant genes, and improve intestinal symptoms.
In clinical practice, patients with Crohn's disease who take mesalazine along with Saccharomyces boulardii show better improvement and fewer adverse reactions compared to those who take the medication alone.
Treatment for Clostridium difficile infection is one of the most challenging issues in clinical practice. Patients often need to continuously take high doses of antibiotics such as vancomycin. However, even with such treatment, the resistance and side effects of potent antibiotics are significant, and there is a high probability of recurrence. A clinical study published in JAMA over 30 years ago demonstrated that patients randomly assigned to take Saccharomyces boulardii had a significantly lower recurrence rate.
Note：Clostridioides difficile infection (CDI) is an infectious disease primarily characterized by diarrhea, ranging from mild, self-resolving diarrhea to severe pseudomembranous colitis, toxic megacolon, and even intestinal perforation. It occurs when the normal intestinal flora is disrupted, allowing the toxin-producing Clostridioides difficile bacteria to proliferate excessively and release toxins.
Similar studies exist for various other conditions besides CDI, such as the treatment intervention for Helicobacter pylori, all showing promising results.
Antifungal properties
Although Saccharomyces boulardii itself is a fungus, it can effectively treat the overgrowth of fungal species in the intestine. This addresses the challenge that other bacterial probiotics cannot intervene in fungal overgrowth.
The greatest risk of fungal overgrowth in the intestines is an increased likelihood of "leaky gut" syndrome. If there are other pathogenic bacteria or toxins present in the intestine at this time, such as bacterial lipopolysaccharides or other fungi like Candida, they can exploit the compromised intestinal barrier and enter the bloodstream.
When immune cells in the bloodstream detect these signals, it can lead to elevated levels of inflammatory cytokines, resulting in various immune system disorders, including various chronic inflammations and allergies.
Candida albicans, is one of the most frequently encountered pathogenic fungi.belongs to the Candida genus and is the most common pathogenic fungus in this genus. It can cause acute or chronic infections of the skin, oral cavity, mucous membranes, and internal organs, known as candidiasis.Candida albicans has a strong survival ability, as it forms a biofilm outside its fungal body. This biofilm acts like an impenetrable barrier, not only facilitating communication between different fungi but also rendering many antifungal drugs ineffective.
But when Candida albicans encounters Saccharomyces boulardii, another fungus, it loses its edge. Saccharomyces boulardii can inhibit the formation of fungal hyphae and prevent Candida from adhering to the intestinal epithelium. Consequently, these pathogenic fungi have no place to establish themselves, and they can't fortify their defenses or form biofilms.
Research shows that Saccharomyces boulardii is highly effective against pathogenic Candida, reducing the formation of Candida biofilms. Various clinical studies have demonstrated that Saccharomyces boulardii is effective against a variety of fungi, including Candida, with significant efficacy.
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