Infection With Clostridioides difficile Attenuated Collagen-Induced Arthritis in Mice and Involved Mesenteric Treg and Th2 Polarization

Abstract

Objectives: Rheumatoid arthritis is an autoimmune disease with multifactorial etiopathogenesis. Among the environmental factors, mucosal infections and the inducing pathobionts are gaining increasing attention. We here set out to explore the gut-joint-axis and the impact of Clostridioides difficile infection on subsequent arthritis. Methods: We combined C. difficile infection in DBA/1J × B10.Q F1 mice with collagen induced arthritis (CIA). Mice were infected via oral gavage and infection was monitored by weight loss, colonic histology, and antibodies against bacteria. Scoring of arthritis was performed macroscopically. Intestinal microbiomes were analyzed and immune responses were monitored via quantification of transcription factor-specific mRNA isolated from the inguinal and mesenteric lymph nodes.Results: Infection with C. difficile VPI 10463 resulted in significant weight loss and severe colitis yet accelerated the reversal towards the original microbiome after antibiotic treatment. Spontaneous clearance of VPI 10463 infection reduced the incidence of subsequent CIA and led to mesenteric T reg and T h2 polarization. However, this attenuating effect was abrogated if VPI 10463 was eradicated via vancomycin followed by fecal microbiota transplantation. Moreover, VPI 10463 infection following the onset of CIA lacked therapeutic potential. Conclusion:Our results demonstrate that infection with C. difficile VPI10463 induced an inflammation of the gut that protected from subsequent arthritis development in mice. Both, microbial changes to the gut and immune cell mobilization and/or polarization may have contributed to arthritis protection. The prospect of potential therapeutic benefits resulting from C. difficile infections or some byproduct thereof call for further experiments that help elucidate exact mechanisms.

Sustained Drug Treatment Alters the Gut Microbiota in Rheumatoid Arthritis

“…However, for the genus Clostridium , Schmidt et al. found that infection with Clostridioides (Clostridium) difficile VPI 10463 induced intestinal inflammation and thus reduced the incidence of collagen induced arthritis (CIA) in mice ( 46 ). Moreover, we identified several other restored species and functions that are not consistent with previous studies, possibly due to treatment differences.…”

Role of Pannexin-1-P2X7R signaling on cell death and pro-inflammatory mediator expression induced by Clostridioides difficile toxins in enteric glia

“…Our murine CDI model is broadly used due to the ability to mimic severe diarrhea presented by humans and was performed as previously described (31)(32)(33)(34)(35). C57BL/6 mice (n=6 for each group) received an antibiotic treatment (0.035 mg per mL gentamicin, 850 U per mL colistin, 0.215 mg per mL metronidazole, and 0.045 mg per mL vancomycin) in the drinking water for 3 days.…”

S100B Inhibition Attenuates Intestinal Damage and Diarrhea Severity During Clostridioides difficile Infection by Modulating Inflammatory Response

“…Our murine CDI model was established as previously described (Chen X. et al, 2008;Moore et al, 2015;Shin et al, 2017;Broecker et al, 2019;Schmidt et al, 2020). This model is broadly used due to the ability to mimic clinical symptoms, such as severe diarrhea, presented by humans with CDI (Chen X. et al, 2008;Moore et al, 2015;Shin et al, 2017;Broecker et al, 2019;Schmidt et al, 2020). C57BL/6 mice (n = 5 for each group) received an antibiotic treatment in the drinking water for 3 days.…”