Protective effect of Saccharomyces boulardii on intestinal mucosal barrier of dextran sodium sulfate-induced colitis in mice

Inflammatory bowel disease (IBD)—a group of chronic conditions including ulcerative colitis (UC) and Crohn’s disease (CD)—affects over 3 million people in the U.S. alone, with symptoms ranging from abdominal pain to severe intestinal damage. A critical factor in IBD development is the intestinal mucosal barrier: a single layer of epithelial cells and tight junctions that keeps harmful bacteria and toxins from entering the bloodstream. When this barrier breaks down, the immune system overreacts, worsening inflammation.

While bacterial probiotics are widely studied for IBD, yeast-based probiotics like Saccharomyces boulardii (Sb) remain underappreciated. Sb is a non-pathogenic yeast used to treat diarrhea and restore gut flora—but its role in IBD, particularly in protecting the mucosal barrier, was unclear. A 2019 study from researchers at Peking University First Hospital set out to change that, using a mouse model of colitis to test Sb’s effects on gut health, inflammation, and flora.

What the Study Did

The team studied 40 male C57BL/6J mice, divided into five groups:

Normal control (no colitis, no treatment)
Colitis model (colitis induced by 2.5% dextran sodium sulfate, or DSS, in drinking water for 7 days)
Sb treatment (colitis + Sb via gavage twice daily)
Mesalazine treatment (colitis + mesalazine, a standard IBD drug)
Combo treatment (colitis + Sb + mesalazine)

To measure Sb’s impact, researchers tracked:

Disease Activity Index (DAI): A score combining weight loss, stool consistency, and blood in stool.
Histological damage: Colon tissue inflammation, crypt loss (damage to gut glands), and immune cell infiltration.
Tight junction proteins: ZO-1 and occludin—molecules that hold epithelial cells together—via immunohistochemistry.
Inflammatory cytokines: TNF-α and IL-8 (markers of immune activation) in plasma.
Gut flora: 16S rRNA sequencing of fecal samples to identify bacterial changes.
Ultrastructure: Tight junction and cell health via transmission electron microscopy (TEM).

Key Findings

Sb delivered comparable benefits to mesalazine—the gold-standard IBD drug—while uniquely modulating gut flora:

1. Sb Reduced Colitis Severity

Compared to the colitis-only group (DAI score: 2.7), Sb lowered DAI to 1.5 (a 43% drop) and cut histological damage by half (from 9.9 to 4.8). Mesalazine had similar effects (DAI: 1.8, histological score: 4.1). Notably, combo therapy didn’t improve outcomes—likely due to the short treatment course (7 days) or potential interactions between Sb and mesalazine.

2. Sb Strengthened the Intestinal Barrier

The colitis group had severely damaged tight junctions, irregular microvilli (tiny gut projections for absorption), and enlarged cell spaces. Sb preserved tight junction integrity:

ZO-1 levels (a key barrier protein) rose from 2.1 to 4.2.
Occludin levels (another barrier protein) increased from 2.2 to 3.5.

TEM images confirmed Sb’s protective effect: treated mice had intact junctions and healthy microvilli, while mesalazine-treated mice still had enlarged cell spaces.

3. Sb Lowered Inflammation

Pro-inflammatory cytokines drive IBD progression—and Sb reduced both:

TNF-α: Dropped from 716 ng/L (colitis group) to 522 ng/L (Sb group).
IL-8: Fell from 129 pg/mL to 106 pg/mL.

These levels matched the normal control group, showing Sb effectively quelled the immune overreaction.

4. Sb Balanced Gut Flora—With a Unique Twist

DSS treatment skewed flora toward Proteobacteria (inflammatory) and away from Firmicutes (beneficial). Sb reversed this:

Increased Bacteroidetes (a fiber-digesting phylum linked to gut health).
Decreased Firmicutes (associated with inflammation).

Most strikingly, Sb specifically boosted the S24-7 family—an uncultured Bacteroidales group that lives exclusively in warm-blooded animals’ guts. S24-7 helps break down carbohydrates (like fiber) and is coated with low-affinity IgA (a type of antibody), marking it as a commensal (friendly) bacteria that supports gut health without causing inflammation.

What This Means for IBD

The study adds strong evidence that Sb is a viable adjunct therapy for IBD. Its benefits likely stem from two key mechanisms:

Immune Regulation: Sb blocks NF-κB and MAPK pathways—molecules that trigger cytokine production and barrier damage. By reducing TNF-α, it directly protects tight junctions.
Flora Modulation: Sb’s ability to target S24-7 is unique. This family is a “commensal workhorse”—it digests fiber, supports nutrient absorption, and doesn’t trigger inflammation. For IBD patients, who often have imbalanced flora, Sb’s S24-7 boost could help restore gut homeostasis.

Limitations to Consider

While promising, the study has caveats:

Mouse Model: Results may not directly translate to humans, as mouse and human gut flora differ.
Short Treatment Course: Combo therapy’s lack of benefit could reflect the 7-day timeline—longer studies are needed.
Acute Colitis: The model mimics acute UC, but human IBD is often chronic.

Takeaways for Patients and Researchers

For patients, Sb offers a safe, yeast-based alternative to bacterial probiotics—with evidence it protects the gut barrier and reduces inflammation. For researchers, the S24-7 finding opens a new frontier: targeting specific commensal bacteria could be a game-changer for IBD therapy.

The study, led by Jin-Pei Dong, Yue Zheng, and colleagues at Peking University First Hospital, was published in the Chinese Medical Journal in 2019. It joins a growing body of work highlighting Sb’s potential—and underscores that yeast probiotics deserve more attention in IBD care.

Dong JP, Zheng Y, Wu T, He Q, Teng GG, Wang HH. Protective effect of Saccharomyces boulardii on intestinal mucosal barrier of dextran sodium sulfate-induced colitis in mice. Chin Med J 2019;132:1951–1958. doi:10.1097/CM9.0000000000000364

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