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Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity
- Source :
- Cellular and Molecular Gastroenterology and Hepatology, Cellular and Molecular Gastroenterology and Hepatology, Vol 10, Iss 2, Pp 225-244 (2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier, 2020.
-
Abstract
- Background & Aims Despite achieving endoscopic remission, more than 20% of inflammatory bowel disease patients experience chronic abdominal pain. These patients have increased rectal transient receptor potential vanilloid-1 receptor (TRPV1) expression, a key transducer of inflammatory pain. Because inflammatory bowel disease patients in remission exhibit dysbiosis and microbial manipulation alters TRPV1 function, our goal was to examine whether microbial perturbation modulated transient receptor potential function in a mouse model. Methods Mice were given dextran sodium sulfate (DSS) to induce colitis and were allowed to recover. The microbiome was perturbed by 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, whereas fecal short-chain fatty acids (SCFAs) were assessed by using targeted mass spectrometry. Results Postinflammatory DSS mice developed visceral and somatic hyperalgesia. Antibiotic administration during DSS recovery induced visceral, but not somatic, hyperalgesia independent of inflammation. FMT of postinflammatory DSS stool into antibiotic-treated mice increased visceral hypersensitivity, whereas FMT of control stool reversed antibiotics’ sensitizing effects. Postinflammatory mice exhibited both increased SCFA-producing species and fecal acetate/butyrate content compared with controls. Capsaicin-evoked calcium responses were increased in naive dorsal root ganglion neurons incubated with both sodium butyrate/propionate alone and with colonic supernatants derived from postinflammatory mice. Conclusions The microbiome plays a central role in postinflammatory visceral hypersensitivity. Microbial-derived SCFAs can sensitize nociceptive neurons and may contribute to the pathogenesis of postinflammatory visceral pain.<br />Graphical abstract
- Subjects :
- 0301 basic medicine
Male
Nociception
Pharmacology
Inflammatory bowel disease
Short-Chain Fatty Acids
FMT, fecal microbial transplant
chemistry.chemical_compound
Feces
Mice
0302 clinical medicine
PCR, polymerase chain reaction
Intestinal Mucosa
Original Research
IBD, inflammatory bowel disease
Dextran Sulfate
Gastroenterology
Nociceptors
Sodium butyrate
Visceral Pain
Abx, antibiotics
Calcium Imaging
DRG, dorsal root ganglion
Hyperalgesia
SCFA, short-chain fatty acid
030211 gastroenterology & hepatology
medicine.symptom
IBS, irritable bowel syndrome
Colon
TRPV1
PBS, phosphate-buffered saline
TRPV Cation Channels
Butyrate
03 medical and health sciences
DSS, dextran sulfate sodium
TRPV1, transient receptor potential vanilloid-1 receptor
medicine
Animals
Humans
lcsh:RC799-869
Colitis
Hepatology
Dorsal Root Ganglion
business.industry
TRPA1, transient receptor potential ankyrin-1 receptor
Visceral pain
DMEM, Dulbecco modified Eagle medium
medicine.disease
Fatty Acids, Volatile
Gastrointestinal Microbiome
Disease Models, Animal
030104 developmental biology
chemistry
HBSS, Hanks’ balanced salt solution
Dysbiosis
lcsh:Diseases of the digestive system. Gastroenterology
DSS Colitis
Colitis, Ulcerative
Microbiome
business
ASV, amplicon sequence variant
Subjects
Details
- Language :
- English
- ISSN :
- 2352345X
- Volume :
- 10
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Gastroenterology and Hepatology
- Accession number :
- edsair.doi.dedup.....ed1dcda8afaf3b78c0b7073da88d285f