Prevotella histicola ameliorates DSS-induced colitis by inhibiting IRE1α-JNK pathway of ER stress and NF-κB signaling

Int Immunopharmacol. 2024 Jun 30:135:112285. doi: 10.1016/j.intimp.2024.112285. Epub 2024 May 18.

Abstract

Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal inflammation regulated by intricate mechanisms. Recently, prebiotics is considered as promising nutritional strategy for the prevention and treatment of IBD. Prevotella histicola (P. histicola), an emerging probiotic, possesses apparently anti-inflammatory bioactivity. However, the role and underlying mechanism of P. histicola on IBD remain unclear. Hence, we probe into the effect of P. histicola on dextran sulfate sodium (DSS)-induced colitis and clarified the potential mechanism. Our results revealed that DSS-induced colonic inflammatory response and damaged epithelial barrier in mice were attenuated by oral administration of P. histicola. Moreover, supplementary P. histicola significantly enriched short-chain fatty acid (SCFA)-producing bacteria (Lactobacillus, and Bacillus) and reduced pathogenic bacteria (Erysipelotrichaceae, Clostridium, Bacteroides) in DSS-induced colitis. Notably, In DSS-treated mice, endoplasmic reticulum stress (ERS) was persistently activated in colonic tissue. Conversely, P. histicola gavage suppressed expansion of endoplasmic reticulum, downregulated PERK-ATF4-CHOP and IRE1α-JNK pathway. In vitro, the P. histicola supernatant eliminated LPS-induced higher production of pro-inflammatory cytokines regulated by NF-κB and impairment of epithelial barrier by inhibiting IRE1α-JNK signaling in Caco-2 cell. In summary, our study indicated that P. histicola mitigated DSS-induced chronic colitis via inhibiting IRE1α-JNK pathway and NF-κB signaling. These findings provide the new insights into the promotion of gut homeostasis and the application potential of P. histicola as a prebiotic for IBD in the future.

Keywords: Endoplasmic reticulum stress; Inflammatory bowel disease; Intestinal barrier; Intestinal microbiota; Prevotella histicola.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Colitis* / chemically induced
  • Colitis* / microbiology
  • Colitis* / pathology
  • Colon / drug effects
  • Colon / immunology
  • Colon / microbiology
  • Colon / pathology
  • Dextran Sulfate*
  • Disease Models, Animal
  • Endoplasmic Reticulum Stress* / drug effects
  • Endoribonucleases* / metabolism
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • NF-kappa B* / metabolism
  • Prevotella*
  • Probiotics / therapeutic use
  • Protein Serine-Threonine Kinases* / metabolism
  • Signal Transduction / drug effects

Substances

  • Dextran Sulfate
  • Protein Serine-Threonine Kinases
  • NF-kappa B
  • Endoribonucleases
  • Ern1 protein, mouse
  • Anti-Inflammatory Agents