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Drugs for Treatment of Constipation-Predominant IBS01:21

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Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone...
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Related Experiment Video

Updated: Jun 16, 2025

Cefoperazone-treated Mouse Model of Clinically-relevant Clostridium difficile Strain R20291
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Receptor-targeted Lactococcus lactis mitigate Clostridioides difficile infection.

Yue Zhang1, Wei Sun2, Hao Wu3

  • 1Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China.

Microbiological Research
|June 13, 2025
PubMed
Summary

Engineered Lactococcus lactis effectively targets Clostridioides difficile infection by producing nisin. Lipid-coated bacteria show enhanced therapeutic potential against recurrent CDI, outperforming current treatments.

Keywords:
AdhesionClostridioides difficile infectionLactococcus lactisNisinRCDIROS-responsive lipid membrane

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Area of Science:

  • Microbiology
  • Biotechnology
  • Gastroenterology

Background:

  • Engineered bacteria are crucial for colorectal disease management.
  • Lactococcus lactis produces nisin to inhibit Clostridioides difficile.
  • Limitations include insufficient nisin production, lack of targeted release, and weak colonization.

Purpose of the Study:

  • To engineer L. lactis for enhanced adherence and therapeutic efficacy.
  • To develop a targeted delivery system for nisin production.
  • To evaluate the efficacy against Clostridioides difficile infection (CDI) and recurrent CDI (rCDI).

Main Methods:

  • Engineered L. lactis (Lla+) expressing C. difficile adhesion protein Cwp8 for increased adherence.
  • Created lipid membrane-coated L. lactis (LCL) using ROS-responsive lipid membrane for encapsulation.
  • Evaluated in vitro and in vivo efficacy in cell models and mouse models of intestinal inflammation.

Main Results:

  • Lla+ showed a 1.3-fold increase in adhesion compared to wild-type L. lactis.
  • LCL demonstrated targeted nisin release in response to inflammatory stimuli and C. difficile.
  • LCL significantly reduced C. difficile survival by 60% and outperformed fidaxomicin in recurrent CDI models.

Conclusions:

  • Encapsulation approach serves as a viable delivery platform for targeting inflamed intestines.
  • Engineered L. lactis offers a promising therapeutic strategy for CDI and rCDI.
  • Probiotics can be expanded as effective pharmaceuticals for gastrointestinal diseases.