Despite achieving endoscopic remission, over 20% of inflammatory bowel disease (IBD) patients experience chronic abdominal pain. These patients have increased rectal transient receptor potential vanilloid-1 [TRPV1] expression, a key transducer of inflammatory pain. Since IBD patients in remission exhibit dysbiosis, and microbial manipulation alters TRPV1 function, our goal was to examine whether microbial perturbation modulated TRP function in a mouse model.
Mice were given dextran sodium sulfate (DSS) to induce colitis and allowed to recover. The microbiome was perturbed using antibiotics as well as fecal microbial transplant (FMT). Visceral and somatic sensitivity were assessed by recording visceromotor responses to colorectal distention and using hot plate/automated Von Frey tests, respectively. Calcium imaging of isolated dorsal root ganglia neurons was used as an in vitro correlate of nociception. The microbiome composition was evaluated via 16S rRNA gene variable region V4 amplicon sequencing, while fecal short chain fatty acids (SCFA) were assessed using targeted mass spectrometry.
Post-inflammatory DSS mice developed visceral and somatic hyperalgesia. Antibiotic administration during DSS recovery induced visceral, but not somatic hyperalgesia independent of inflammation. FMT of post-inflammatory DSS stool into antibiotic-treated mice increased visceral hypersensitivity, while FMT of control stool reversed antibiotics’ sensitizing effects. Post-inflammatory mice exhibited both increased SCFA-producing species, and fecal acetate/butyrate content compared to controls. Capsaicin-evoked calcium responses were increased in naïve dorsal root ganglion neurons incubated with both sodium butyrate/propionate alone, and with colonic supernatants derived from post-inflammatory mice.
The microbiome plays a central role in post-inflammatory visceral hypersensitivity. Microbial-derived SCFA can sensitize nociceptive neurons and may contribute to the pathogenesis of post-inflammatory visceral pain.

Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

References

PubMed