{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:35:48Z","timestamp":1790858148818,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>The vagus nerve has been implicated in mediating behavioural effects of the gut microbiota on the central nervous system. This study examined whether the secretory products of commensal gut bacteria can modulate the excitability of vagal afferent neurons with cell bodies in nodose ganglia.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Cysteine proteases from commensal bacteria increased the excitability of vagal afferent neurons via activation of protease\u2010activated receptor 2 and modulation of the voltage dependence of Na<jats:sup>+<\/jats:sup> conductance activation.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Lipopolysaccharide, a component of the cell wall of gram\u2010negative bacteria, increased the excitability of nodose ganglia neurons via TLR4\u2010dependent activation of nuclear factor kappa B.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our study identified potential mechanisms by which gut microbiota influences the activity of vagal afferent pathways, which may in turn impact on autonomic reflexes and behaviour.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Behavioural studies have implicated vagal afferent neurons as an important component of the microbiota\u2010gut\u2010brain axis. However, the mechanisms underlying the ability of the gut microbiota to affect vagal afferent pathways are unclear. We examined the effect of supernatant from a community of 33 commensal gastrointestinal bacterial derived from a healthy human donor (microbial ecosystem therapeutics; MET\u20101) on the excitability of mouse vagal afferent neurons. Perforated patch clamp electrophysiology was used to measure the excitability of dissociated nodose ganglion (NG) neurons. NG neuronal excitability was assayed by measuring the amount of current required to elicit an action potential, the rheobase. MET\u20101 supernatant increased the excitability of NG neurons by hyperpolarizing the voltage dependence of activation of Na<jats:sup>+<\/jats:sup> conductance. The increase in excitability elicited by MET\u20101 supernatant was blocked by the cysteine protease inhibitor E\u201064 (30\u00a0n<jats:sc>m<\/jats:sc>). The protease activated receptor\u20102 (PAR<jats:sub>2<\/jats:sub>) antagonist (GB\u00a083, 10\u00a0\u03bc<jats:sc>m<\/jats:sc>) also blocked the effect of MET\u20101 supernatant on NG neurons. Supernatant from <jats:italic>Lactobacillus paracasei<\/jats:italic> 6MRS, a component of MET\u20101, recapitulated the effect of MET\u20101 supernatant on NG neurons. Lastly, we compared the effects of MET\u20101 supernatant and lipopolysaccharide (LPS) from <jats:italic>Escherichia coli<\/jats:italic> 05:B5 on NG neuron excitability. LPS increased the excitability of NG neurons in a toll\u2010like receptor 4 (TLR<jats:sub>4<\/jats:sub>)\u2010dependent and PAR<jats:sub>2<\/jats:sub>\u2010independent manner, whereas the excitatory effects of MET\u20101 supernatant were independent of TLR<jats:sub>4<\/jats:sub> activation. Together, our findings suggest that cysteine proteases from commensal bacteria increase the excitability of vagal afferent neurons by the activation of PAR<jats:sub>2<\/jats:sub>.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp279075","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T16:54:21Z","timestamp":1583427261000},"page":"2137-2151","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Protease\u2010dependent excitation of nodose ganglion neurons by commensal gut bacteria"],"prefix":"10.1113","volume":"598","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8712-2419","authenticated-orcid":false,"given":"Sabindra","family":"Pradhananga","sequence":"first","affiliation":[{"name":"Gastrointestinal Disease Research Unit (GIDRU) Queen's University  Kingston Ontario K7L2V7 Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayssar 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