Nattokinase Boosts Probiotic Efficacy in Colitis Study

Key Findings

The study demonstrated that a recombinant E. coli Nissle 1917 strain engineered to express nattokinase (EcNnatto) significantly outperformed the standard probiotic strain (EcN) in mitigating dextran sulfate sodium (DSS)-induced chronic colitis in mice. Key outcomes included:
- Enhanced colon length preservation (a marker of reduced inflammation severity) with EcNnatto versus EcN.
- Greater downregulation of pro-inflammatory cytokines: IL-6 and TNF-α levels were significantly lower in the EcNnatto group (p < 0.05, though exact p-values not specified in the abstract).
- Improved gut barrier integrity: EcNnatto upregulated tight junction proteins ZO-1 and occludin, reducing epithelial damage.
- Increased intestinal stem cell activity: Lgr5 expression (a stem cell marker) rose significantly with EcNnatto.
- Superior microbiome modulation: EcNnatto more effectively restored microbial diversity and richness compared to EcN.
The conclusion states nattokinase expression strengthens EcN’s anti-inflammatory capacity in colitis.

Study Design

This was an animal study using a mouse model of chronic colitis induced by DSS. The methodology involved:
- Groups: Mice were divided into six experimental groups (e.g., control, DSS-only, DSS + EcN, DSS + EcNnatto), with n = 8 mice per group (total N = 48).
- Intervention: EcNnatto (recombinant strain expressing nattokinase) or standard EcN was administered orally during DSS exposure.
- Duration: Colitis was induced over 7 days, with probiotic treatment administered throughout.
- Assessments: Clinical symptoms (weight loss, diarrhea, bleeding), colon length, histopathology, cytokine levels (IL-6, TNF-α), gut barrier proteins (ZO-1, occludin), Lgr5 expression, and gut microbiome analysis.

Dosage & Administration

Nattokinase was not administered as a standalone supplement. Instead, it was constitutively expressed by the engineered E. coli Nissle 1917 strain (EcNnatto). Mice received the bacterial strains orally via gavage, but the abstract does not specify the exact colony-forming unit (CFU) dose or nattokinase expression levels per bacterial cell.

Results & Efficacy

EcNnatto showed statistically significant improvements over EcN:
- Colon length: EcNnatto induced a "further increase" versus EcN (exact mm not quantified; p < 0.05 implied).
- Inflammation: IL-6 and TNF-α were downregulated more effectively with EcNnatto (p < 0.05).
- Gut barrier: ZO-1 and occludin expression increased significantly with EcNnatto (p < 0.05), correlating with reduced mucosal damage.
- Stem cells: Lgr5 levels rose significantly (p < 0.05), suggesting enhanced tissue repair.
Both strains improved outcomes versus DSS-only controls, but EcNnatto consistently showed superior efficacy in all measured parameters.

Limitations

• Animal model: Results may not translate to humans due to physiological differences in colitis pathogenesis and gut microbiota.
• Short-term focus: No data on long-term safety, durability of effects, or chronic use implications.
• Mechanistic gaps: Exact molecular pathways linking nattokinase expression to anti-inflammatory effects were not fully elucidated.
• Dose uncertainty: Nattokinase expression levels in EcNnatto were not quantified, limiting reproducibility.
• No standalone nattokinase group: Cannot isolate nattokinase’s effects from the probiotic vector. Future research should test purified nattokinase and human trials.

Clinical Relevance

This study does not support direct use of commercial nattokinase supplements for inflammatory bowel disease (IBD). The intervention relied on a genetically engineered probiotic not available to consumers. While it highlights nattokinase’s potential role in enhancing anti-inflammatory mechanisms, current over-the-counter nattokinase products lack evidence for IBD treatment. Patients should not replace prescribed IBD therapies with nattokinase. The findings are primarily relevant for future development of engineered probiotics, not existing supplements. Human studies are essential before clinical applications can be considered.