Paraclostridium bifermentans exacerbates pathosis in a mouse model of ulcerative colitis

PLoS One. 2018 May 21;13(5):e0197668. doi: 10.1371/journal.pone.0197668. eCollection 2018.

Abstract

Although it has been recognized that intestinal bacteria play an important role in the pathology of human ulcerative colitis (UC), specific pathogenic bacteria for UC have not been identified. We investigated the influence of Paraclostridium bifermentans PAGU1678 strain on the pathology of a UC mouse model and found it increased UC pathosis scores such as loose and bloody stools, reduced diversity of fecal flora, disappearance of the crypt structure of distal colon tissue, destruction of intestinal epithelial cells, and atrophy of the colon. Furthermore, we observed an increase in COX-2, TNF-α, IL-6, IL-1, and IL-17 expression and a decrease in Foxp3 and SOCS3 expression, as inflammation-related factors and inflammatory cytokines, a decrease in the concentration of short chain fatty acids (acetic acid, propionic acid, and butyric acid) in feces, and an increase of intestinal mucosal myeloperoxidase activity. These results suggest that P. bifermentans PAGU1678 is a pathology-exacerbating factor in a mouse model of UC. This study is the first to demonstrate exacerbation of the pathological condition in a mouse model of UC by a single bacterial strain.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clostridiales / pathogenicity*
  • Colitis, Ulcerative / etiology
  • Colitis, Ulcerative / microbiology*
  • Colitis, Ulcerative / pathology
  • Colon / metabolism
  • Colon / microbiology
  • Cytokines / genetics
  • Cytokines / metabolism
  • Dextran Sulfate / toxicity
  • Disease Models, Animal
  • Fatty Acids, Volatile / metabolism
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Cytokines
  • Fatty Acids, Volatile
  • Inflammation Mediators
  • RNA, Messenger
  • Dextran Sulfate
  • Peroxidase

Grants and funding

This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (https://www.jsps.go.jp/j-grantsinaid/index.html) grant numbers 25460177 and 21590138 to YK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.