E. coli Nissle 1917: A Breakthrough Probiotic for Ulcerative Colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) characterized by inflammation of the colon's mucosal lining, leading to symptoms such as abdominal pain, diarrhea, and rectal bleeding. The etiology of UC is multifactorial, involving genetic predisposition, environmental factors, and immune system dysregulation. Traditional management strategies include aminosalicylates, corticosteroids, and immunosuppressants. However, the advent of probiotic therapy has introduced new avenues for managing UC symptoms. Among these, Escherichia coli Nissle 1917 (EcN) has emerged as a promising probiotic strain for UC management.

What is E. coli Nissle1917

Discovery and History

In 1917, during World War I, German physician Alfred Nissle isolated a non-pathogenic strain of E. coli from the feces of a soldier who remained free from dysentery amidst an outbreak. This strain, later named E. coli Nissle 1917, exhibited probiotic properties and has since been utilized in various gastrointestinal treatments.

Unique Characteristics

EcN 1917 is distinguished from pathogenic E. coli strains by its lack of virulence factors, rendering it non-pathogenic. Its genome comprises genes that confer fitness and survival advantages in the gut environment, such as the ability to adhere to intestinal mucosa and produce antimicrobial substances. These properties enable EcN to colonize the gut effectively and support microbiome balance.

Fig. 1 E. coli on Petri dish. (Creative Biolabs Authorized)

Mechanisms of Action in Ulcerative Colitis Management

Anti-inflammatory Effects

EcN 1917 modulates the gut immune system by reducing the production of pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6). This modulation prevents excessive immune responses that contribute to UC pathology. Additionally, EcN influences dendritic cell maturation and promotes the development of regulatory T-cells, further contributing to immune homeostasis.

Enhancement of Intestinal Barrier Function

The integrity of the intestinal barrier is crucial in preventing the translocation of harmful substances. EcN 1917 strengthens tight junction proteins, thereby reducing intestinal permeability. It also stimulates mucin production, enhancing the protective mucus layer of the gut lining. These actions collectively fortify the intestinal barrier, mitigating inflammation associated with UC.

Competitive Exclusion of Pathogens

EcN 1917 produces antimicrobial peptides that inhibit the growth of pathogenic bacteria, such as Salmonella spp. By occupying ecological niches within the gut, EcN competes with harmful microbes, thereby supporting a balanced gut microbiome and preventing dysbiosis—a condition often linked to UC exacerbations.

Clinical Evidence Supporting EcN 1917 for UC

Several clinical trials have evaluated the efficacy of EcN 1917 in UC management. A pivotal double-blind study compared EcN to mesalazine, a standard UC treatment, in maintaining remission. The results demonstrated that EcN was as effective as mesalazine, with relapse rates of 36.4% in the EcN group and 33.9% in the mesalazine group. Both treatments exhibited good safety profiles and tolerability.

Another study involving pediatric patients aged 11 to 18 years assessed EcN's efficacy in maintaining UC remission. Over one year, relapse rates were 25% in the EcN group and 30% in the mesalazine group, indicating comparable effectiveness. No serious adverse events were reported, underscoring EcN's safety in younger populations.

Safety Profile and Comparison with Traditional Therapies

EcN 1917 has demonstrated a favorable safety profile in both short-term and long-term studies. Unlike immunosuppressive drugs, which carry risks of systemic infections and malignancies, EcN's use has not been associated with severe side effects. This positions EcN as a potential complementary or alternative therapy for UC patients, particularly those who may not tolerate conventional treatments well.

Aspect E. coli Nissle 1917 (EcN 1917) Traditional Therapies (Immunosuppressants, Corticosteroids, Mesalazine)
Safety Demonstrated a favorable safety profile in both short-term and long-term studies. May pose risks of immunosuppression, infections, and other systemic effects.
Effectiveness Comparable to mesalazine in maintaining remission in UC patients. Effective in managing UC symptoms and maintaining remission.
Side Effects Not associated with severe side effects. Potentially severe side effects, including increased risk of infections, osteoporosis, and liver toxicity.
Long-term Risks No evidence of systemic infections or malignancies. Long-term use linked to risks such as malignancies and adrenal insufficiency.
Potential for Combination Can be combined with other microbiome-targeting strategies. Often used in combination therapy but with increased risk of adverse effects.

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Applications and Future Directions of EcN 1917

Expanding Use Beyond Ulcerative Colitis

EcN 1917 has shown potential benefits beyond UC, including applications in Crohn's disease, irritable bowel syndrome (IBS), and pouchitis by modulating gut microbiota and reducing inflammation.

Combination with Prebiotics and Microbiome Therapies

EcN's efficacy may be enhanced when combined with prebiotics like inulin, promoting better colonization. Personalized microbiome approaches using gut microbiome sequencing could optimize EcN-based therapies for individual patients.

Future Research and Next-Generation Probiotics

Advances in genetic engineering aim to enhance EcN's therapeutic effects. Emerging postbiotic therapies focus on isolating beneficial compounds produced by EcN, offering safer alternatives for gut health management. Further clinical research will determine its full potential in precision medicine.

Conclusion

EcN 1917 stands as a significant advancement in probiotic therapy for ulcerative colitis management. Its multifaceted mechanisms—including anti-inflammatory effects, enhancement of intestinal barrier function, and competitive exclusion of pathogens—underscore its therapeutic potential. Clinical evidence supports its efficacy and safety, positioning EcN as a viable option in UC management strategies. Continued research and patient-centered applications are essential to fully harness the benefits of probiotics like EcN in clinical settings.

Creative Biolabs offers a comprehensive range of services and products related to EcN 1917:

  • One-stop Solutions for E. coli Nissle 1917: including gene knockout and knock-in services, constructing recombinant strains, and using engineered EcN bacteria as imaging vectors.
  • Engineered E. coli Nissle 1917 for Disease-targeting Therapy: by modifying its genome, EcN 1917 can be designed to express therapeutic molecules. This engineered approach leverages EcN 1917's natural probiotic properties, enhancing its potential as a platform for microbiome-based interventions in gastrointestinal and systemic diseases.
  • E. coli Nissle 1917 Probiotic Strains: these strains undergo rigorous purity and viability testing to ensure high stability and functional integrity. They are suitable for a variety of research applications, including probiotic efficacy studies, gut microbiota analysis, and novel therapeutic development.

FAQs

How does EcN 1917 interact with the gut virome?

EcN 1917 can influence the gut virome by modulating bacteriophage populations, potentially impacting bacterial diversity and stability in the microbiome. Research on its interactions with phages could provide insights into microbiome regulation.

Can EcN 1917 be engineered to deliver therapeutic biomolecules?

Synthetic biology approaches allow the modification of EcN 1917 to produce bioactive compounds, enzymes, or immunomodulatory molecules. This bioengineering potential makes it a promising candidate for next-generation live biotherapeutics in precision medicine.

Resources

Reference

  1. Scaldaferri, Franco, et al. "Role and mechanisms of action of Escherichia coli Nissle 1917 in the maintenance of remission in ulcerative colitis patients: an update." World journal of gastroenterology 22.24 (2016): 5505. https://doi.org/10.3748/wjg.v22.i24.5505
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For Research Use Only. Not intended for use in food manufacturing or medical procedures (diagnostics or therapeutics). Do Not Use in Humans.

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