Secreted NF-κB suppressive microbial metabolites modulate gut inflammation

Cell Rep. 2022 Apr 12;39(2):110646. doi: 10.1016/j.celrep.2022.110646.


Emerging evidence suggests that microbiome-host crosstalk regulates intestinal immune activity and predisposition to inflammatory bowel disease (IBD). NF-κB is a master regulator of immune function and a validated target for the treatment of IBD. Here, we identify five Clostridium strains that suppress immune-mediated NF-κB activation in epithelial cell lines, PBMCs, and gut epithelial organoids from healthy human subjects and patients with IBD. Cell-free culture supernatant from Clostridium bolteae AHG0001 strain, but not the reference C. bolteae BAA-613 strain, suppresses inflammatory responses and endoplasmic reticulum stress in gut epithelial organoids derived from Winnie mice. The in vivo responses to Clostridium bolteae AHG0001 and BAA-613 mirror the in vitro activity. Thus, using our in vitro screening of bacteria capable of suppressing NF-κB in the context of IBD and using an ex vivo organoid-based approach, we identify a strain capable of alleviating colitis in a relevant pre-clinical animal model of IBD.

Keywords: CP: Immunology; CP: Microbiology; Clostridium; Crohn’s disease; IBD; NF-κB; anti-inflammatory; bioactive; gut microbiota; ulcerative colitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Clostridiales
  • Colitis* / metabolism
  • Humans
  • Inflammation / metabolism
  • Inflammatory Bowel Diseases* / metabolism
  • Intestinal Mucosa / metabolism
  • Mice
  • NF-kappa B / metabolism


  • NF-kappa B

Supplementary concepts

  • Clostridium bolteae