Effect of Doxycycline in Decreasing the Severity of Clostridioides difficile Infection in Mice

Background: Doxycycline possesses antibacterial activity against Clostridioides difficile and anti-inflammatory effects. Materials and Methods: The influence of doxycycline on the development of CDI was studied in an established animal model of CDI using C57BL/6 mice. Results: Mice intraperitoneally administered doxycycline had higher cecum weight (1.3 +/- 0.1 vs. 0.5 +/- 0.1 g; p < 0.001) and less body weight reduction (0.7 +/- 0.5 g vs. -17.4 +/- 0.2 g; p < 0.001) than untreated mice infected with C. difficile. Oral doxycycline, metronidazole, or vancomycin therapy resulted in less body weight reduction in mice with CDI than in untreated mice (1.1 +/- 0.1 g, 1.3 +/- 0.2 g, 1.2 +/- 0.1 g, vs. 2.9 +/- 0.3 g; p < 0.001). Doxycycline therapy led to lower expression levels of inflammatory cytokines, such as macrophage inflammatory protein-2 (0.4 +/- 0.1 vs. 2.9 +/- 1.3, p = 0.02), and higher levels of zonula occludens-1 (1.2 +/- 0.1 vs. 0.8 +/- 0.1, p = 0.02) in colonic tissues than in untreated mice. Conclusions: Concurrent intraperitoneal administration of doxycycline and oral C. difficile challenge does not aggravate the disease severity of CDI, and oral doxycycline may be a potential therapeutic option for CDI.

Automated summary

Doxycycline has a positive impact on the development of CDI, reducing the severity of the disease, and may be a potential therapeutic option for CDI.