Anxiolytic effects of Enterococcus faecalis 2001 on a mouse model of colitis

Sci Rep. 2024 May 21;14(1):11519. doi: 10.1038/s41598-024-62309-3.

Abstract

Ulcerative colitis (UC) is a refractory inflammatory bowel disease, which is known to cause psychiatric disorders such as anxiety and depression at a high rate in addition to peripheral inflammatory symptoms. However, the pathogenesis of these psychiatric disorders remains mostly unknown. While prior research revealed that the Enterococcus faecalis 2001 (EF-2001) suppressed UC-like symptoms and accompanying depressive-like behaviors, observed in a UC model using dextran sulfate sodium (DSS), whether it has an anxiolytic effect remains unclear. Therefore, we examined whether EF-2001 attenuates DSS-induced anxiety-like behaviors. Treatment with 2% DSS for seven days induced UC-like symptoms and anxiety-like behavior through the hole-board test, increased serum lipopolysaccharide (LPS) and corticosterone concentration, and p-glucocorticoid receptor (GR) in the prefrontal cortex (PFC), and decreased N-methyl-D-aspartate receptor subunit (NR) 2A and NR2B expression levels in the PFC. Interestingly, these changes were reversed by EF-2001 administration. Further, EF-2001 administration enhanced CAMKII/CREB/BDNF-Drebrin pathways in the PFC of DSS-treated mice, and labeling of p-GR, p-CAMKII, and p-CREB showed colocalization with neurons. EF-2001 attenuated anxiety-like behavior by reducing serum LPS and corticosterone levels linked to the improvement of UC symptoms and by facilitating the CAMKII/CREB/BDNF-Drebrin pathways in the PFC. Our findings suggest a close relationship between UC and anxiety.

Keywords: Anxiety; BDNF; Colitis; Corticosterone; Drebrin; EF-2001.

MeSH terms

  • Animals
  • Anti-Anxiety Agents* / pharmacology
  • Anti-Anxiety Agents* / therapeutic use
  • Anxiety / drug therapy
  • Colitis / chemically induced
  • Colitis / drug therapy
  • Colitis / metabolism
  • Colitis, Ulcerative / drug therapy
  • Colitis, Ulcerative / metabolism
  • Colitis, Ulcerative / microbiology
  • Corticosterone / blood
  • Dextran Sulfate* / toxicity
  • Disease Models, Animal*
  • Enterococcus faecalis*
  • Lipopolysaccharides
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prefrontal Cortex / metabolism