Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice |
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| Authors: | Mnica Aguilera Valerio Rossini Ana Hickey Donjete Simnica Fiona Grady Valeria D Felice Amy Moloney Lauren Pawley Aine Fanning Lorraine McCarthy Siobhan M O&#x;Mahony John F Cryan Ken Nally Fergus Shanahan Silvia Melgar |
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| Affiliation: | 1.APC Microbiome Ireland, University College Cork, T12 YT20 Cork, Ireland; (M.A.); (V.R.); (A.H.); (D.S.); (F.G.); (V.D.F.); (A.M.); (L.P.); (A.F.); (L.M.); (S.M.O.); (J.F.C.); (K.N.); (F.S.);2.School of Biochemistry and Cell Biology, University College Cork, T12 YT20 Cork, Ireland;3.Department of Anatomy and Neuroscience, University College Cork, T12 YT20 Cork, Ireland |
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| Abstract: | Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain–gut interactions, but their role in microbiota–neuro–immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut–neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent. |
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| Keywords: | gut– brain axis gut commensal microbiota immune system inflammasome |
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