Engineered Escherichia coli Nissle 1917 secreting anti-TNF-α nanobody as a single-strain live biotherapeutic for inflammatory bowel disease - Report - MDSpire

Engineered Escherichia coli Nissle 1917 secreting anti-TNF-α nanobody as a single-strain live biotherapeutic for inflammatory bowel disease

  • By

  • Qiumei Zhu

  • Shitao Feng

  • Zhende Yan

  • Zijian Wang

  • Xinran Huang

  • Changning Sun

  • Bingqiang Zhang

  • Xinrui Li

  • Yuchao Gu

  • July 2, 2026

  • 0 min

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Clinical Report: Genetically Modified Escherichia coli Nissle 1917 Producing Anti-TNF-α Nanobody

Overview

This study presents EcN-MT1, a genetically engineered probiotic that secretes an anti-TNF-α nanobody. The findings indicate improved disease outcomes in a murine model of colitis.

Background

Inflammatory bowel disease (IBD) is a chronic condition with increasing prevalence. Current treatments often lead to systemic side effects and inadequate mucosal targeting. Engineered probiotics like Escherichia coli Nissle 1917 (EcN) represent a novel approach to deliver localized therapies directly within the inflamed gut.

Data Highlights

ParameterResult
Secretion of MT1 (mg/L)4.6
Binding Affinity (EC50 nM)27.9
Weight Loss AttenuationSignificant
DAI ImprovementSignificant
Colon Length PreservationSignificant

Key Findings

  • EcN-MT1 demonstrated high secretion levels of the anti-TNF-α nanobody MT1.
  • The engineered strain outperformed genomic integrants in therapeutic efficacy without growth impairment.
  • Binding simulations confirmed stable interactions between MT1 and murine TNF-α.
  • Oral administration of EcN-MT1 significantly improved disease activity index (DAI) scores in a murine colitis model.
  • Histopathological analysis showed reduced mucosal damage and immune cell infiltration with EcN-MT1 treatment.
  • EcN-MT1 restored gut microbial diversity and enriched beneficial taxa associated with anti-inflammatory effects.

Clinical Implications

The development of EcN-MT1 offers a strategy for localized treatment of IBD.

Conclusion

EcN-MT1 achieves localized TNF-α neutralization while promoting gut health.

Related Resources & Content

  1. Journal of Gastroenterology, 2018 -- Emerging Therapeutic Strategies for Inflammatory Bowel Disorders
  2. Journal of Gastroenterology, 2011 -- Investigating the Therapeutic Impact of Probiotic Escherichia coli Nissle 1917
  3. The Journal of Infectious Diseases, 2023 -- Strategic Development of Live Biotherapeutic Products to Prevent Clostridioides difficile Infections
  4. Frontiers in Immunology — Noncanonical NF-κB pathway driven inflammation across multiple cellular compartments identifies NIK as a therapeutic target for inflammatory bowel disease
  5. Living guideline for pharmacological management of moderate-to-severe ulcerative colitis
  6. New AGA guideline streamlines Crohn’s disease treatment
  7. https://mediacdn.gi.org/giorg/wp-content/uploads/2025/08/19164340/EBGI_Aug25AlKazzi.pdf
  8. AGA Living Clinical Practice Guideline on the Pharmacologic Management of Moderate-to-Severe Crohn's Disease - PubMed
  9. ECCO Guidelines on Therapeutics in Crohn’s Disease: Medical Treatment | Journal of Crohn's and Colitis | Oxford Academic
  10. Study Details | NCT03011268 | Anti-tumor Necrosis Factor in Patients With Ulcerative Colitis in Clinical Remission: to Continue or Not? | ClinicalTrials.gov
  11. Mirikizumab four-year sustained and durable efficacy and safety in ulcerative colitis: Final findings from the LUCENT-3 open-label extension study - PubMed
  12. An Inflammation-Targeting Engineered Probiotic Escherichia coli Nissle 1917 with High Anti-TNF-α Nanobody Secretion Efficacy Alleviates Ulcerative Colitis - PubMed
  13. Nitrate-responsive genetically engineered probiotics locally release TNF-α nanobodies against inflammatory bowel disease - ScienceDirect
  14. DEVELOPMENT OF A NEXT GENERATION ENGINEERED LIVE MICROBIOME BIOTHERAPEUTIC, E COLI NISSLE 1917-TTR, FOR ULCERATIVE COLITIS | Inflammatory Bowel Diseases | Oxford Academic
  15. Early Clinical Trials With Live Biotherapeutic Products: Chemistry, Manufacturing, and Control Information | FDA

Original Source(s)

Engineered Escherichia coli Nissle 1917 secreting anti-TNF-α nanobody as a single-strain live biotherapeutic for inflammatory bowel disease

  • by Qiumei Zhu, Shitao Feng, Zhende Yan, Zijian Wang, Xinran Huang, Changning Sun, Bingqiang Zhang, Xinrui Li, Yuchao Gu

  • July 2, 2026

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