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Engineering Escherichia coli Nissle 1917 Carrying PD1 Agonists Resolves Intestinal Inflammation via Local Immune

Mengyuan Hu1, Tingting Li1, Mengmeng Xu2

  • 1Department of Pathology, The First Affiliated Hospital, State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection& School for Radiological and Interdisciplinary Sciences (RAD-X), Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Cancer institute, Suzhou medical college, Soochow University, Suzhou, Jiangsu 215123, China.

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Summary
This summary is machine-generated.

This study developed a probiotic Escherichia coli Nissle 1917 (EcN) therapy to suppress abnormal T-cell activation, reducing intestinal inflammation and promoting gut repair in mouse models.

Keywords:
Escherichia coli Nissle 1917PD1 agonistsinflammatory bowel diseaseouter membrane vesiclesradiation enteritis

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Area of Science:

  • Immunology
  • Gastroenterology
  • Microbiology

Background:

  • Intestinal inflammation, often driven by immunological imbalance, lacks effective treatments.
  • Radiation-induced intestinal injury models reveal abnormal T-cell activation as a key driver of inflammation.
  • Targeting the PD1 signaling pathway offers a potential strategy to modulate T-cell responses.

Purpose of the Study:

  • To investigate the therapeutic potential of a PD1 agonist-displaying probiotic Escherichia coli Nissle 1917 (EcNMP1-M) for radiation-induced enteritis.
  • To evaluate the anti-inflammatory and intestinal repair effects of EcNMP1-M in mouse models of intestinal injury.
  • To assess the impact of EcNMP1-M on gut microbiota composition and diversity.

Main Methods:

  • Utilized a radiation-induced intestinal injury model and two additional mouse models.
  • Engineered EcNMP1-M encapsulated in Eudragit L100-55 to express PD1 agonists via bacterial outer membrane vesicles (OMVs).
  • Assessed immune activation, inflammatory cytokines, intestinal epithelial barrier integrity, and gut microbiome diversity (16S rDNA sequencing).

Main Results:

  • EcNMP1-M significantly inhibited excessive immune activation and reduced inflammatory cytokines by targeting the PD1 pathway.
  • Treatment with EcNMP1-M promoted the expression of proteins crucial for intestinal epithelial barrier integrity, improving gut function.
  • EcNMP1-M enhanced gut microbiota diversity, increased beneficial bacteria, and decreased harmful bacteria in colitis models.

Conclusions:

  • EcNMP1-M demonstrates significant anti-inflammatory and intestinal repair capabilities in preclinical models.
  • This probiotic-based therapy shows promise for localized immunosuppression in radiation-induced enteritis and inflammatory bowel disease.
  • The findings suggest a potential for clinical application of this novel EcN-based therapeutic strategy.