1. Colitis-Induced Microbial Perturbation Promotes Postinflammatory Visceral Hypersensitivity
- Author
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Nicolas Esquerre, Dominique Bihan, Alana Schick, Yasmin Nasser, Manon Defaye, Fernando A. Vicentini, Lilian Basso, Keith A. Sharkey, Christophe Altier, Simon A. Hirota, Ian A. Lewis, Nina L. Cluny, Humberto Jijon, and Markus B. Geuking
- 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 - 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., Graphical abstract
- Published
- 2020