The Norepinephrine-QseC Axis Aggravates F. nucleatum-associated Colitis Through Interkingdom Signaling
Ling Zhang1,2, Guimei Chen1,2, Xianghao Zeng1,2
1Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, 637000, P.R. China.
Inflammatory Bowel Diseases
|March 29, 2024
Summary
Chronic stress hormone norepinephrine (NE) enhances Fusobacterium nucleatum pathogenicity via the QseC pathway, worsening inflammatory bowel disease (IBD) in mice. Targeting this NE-QseC axis may offer new IBD microbiota management strategies.
Area of Science:
- Microbiology
- Immunology
- Gastroenterology
Background:
- Inflammatory bowel disease (IBD) is linked to Fusobacterium nucleatum.
- Chronic stress is a risk factor for IBD exacerbation.
- The role of norepinephrine (NE) in F. nucleatum pathogenicity remains unclear.
Purpose of the Study:
- To investigate if norepinephrine enhances F. nucleatum pathogenicity.
- To elucidate the mechanism by which NE affects F. nucleatum.
- To evaluate the therapeutic potential of targeting the NE-QseC interaction in a colitis model.
Main Methods:
- Transcriptome sequencing identified NE-regulated genes in F. nucleatum.
- Affinity testing and molecular docking predicted NE-QseC binding.
- In vitro and in vivo (DSS-induced colitis mouse model) assays assessed pathogenicity and therapeutic interventions.
Main Results:
- Norepinephrine directly binds to QseC, upregulating quorum sensing and virulence genes (FadA, FomA, Fap2) in F. nucleatum.
- NE enhances F. nucleatum intestinal invasion and host inflammatory cytokine (IL-6, IL-1β) expression, worsening colitis.
- The QseC inhibitor LED209 counteracted NE effects, restoring beneficial bacteria and attenuating colitis.
Conclusions:
- The NE-QseC axis drives interkingdom signaling, increasing F. nucleatum pathogenicity and exacerbating IBD in mice.
- QseC inhibition presents a potential therapeutic target for microbiota modulation in IBD under chronic stress conditions.
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