Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity.

Area of Science:

• Gastroenterology
• Neuroscience
• Microbiology

Background:

• Over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain despite endoscopic remission.
• These patients show increased rectal transient receptor potential vanilloid-1 receptor (TRPV1) expression, a key pain transducer.
• IBD-associated dysbiosis and microbial alterations of TRPV1 function suggest a link between the microbiome and pain.

Purpose of the Study:

• To investigate if microbial perturbation modulates transient receptor potential (TRP) function in a mouse model of post-inflammatory pain.
• To determine the role of the gut microbiome in visceral hypersensitivity following colitis.
• To explore the mechanisms by which microbial metabolites contribute to pain sensitization.

Main Methods:

• Dextran sodium sulfate (DSS) induced colitis in mice, followed by recovery.
• Microbiome perturbation using antibiotics and fecal microbial transplant (FMT).
• Assessment of visceral and somatic sensitivity, calcium imaging of neurons, 16S rRNA sequencing, and short-chain fatty acid (SCFA) analysis.

Main Results:

• Post-colitis mice exhibited visceral and somatic hyperalgesia.
• Antibiotic treatment during recovery induced visceral hyperalgesia, which was transferable via FMT.
• Increased SCFA-producing bacteria and fecal SCFAs (acetate, butyrate) were observed in post-inflammatory mice, correlating with increased neuronal excitability.

Conclusions:

• The gut microbiome is central to post-inflammatory visceral hypersensitivity.
• Microbial-derived SCFAs can sensitize nociceptive neurons.
• Targeting the microbiome and its metabolites may offer therapeutic strategies for chronic pain in IBD.