{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:35:10Z","timestamp":1790166910115,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T00:00:00Z","timestamp":1740268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010109","name":"Medizinische Universit\u00e4t Graz","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100010109","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["613979"],"award-info":[{"award-number":["613979"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The use of analgosedatives in critically ill patients carries the risk of impairing gastrointestinal (GI) propulsion and could thereby lead to sepsis. The gut microbiota can influence GI motility, but whether GI microbial dysbiosis modifies GI peristalsis impairment by analgosedative drugs has not yet been analysed. This question was addressed in the guinea pig small intestine following a decrease of bacterial load by antibiotic pretreatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>Guinea pigs were enorally (within the mouth) pretreated with meropenem, neomycin and vancomycin, and antibiotic\u2010induced decrease of bacterial load was confirmed by 16S rDNA sequencing. Peristalsis in the isolated guinea pig small intestine was evaluated by determining the pressure threshold at which a peristaltic wave is triggered. The expression of factors that may be relevant to communication between GI microbiota and the motor system was examined at the mRNA (quantitative (q)PCR]) and\/or protein (enzyme\u2010linked immunosorbent assay [ELISA]) level.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Antibiotic treatment disturbed the small intestinal microbiome as shown by decrease of bacterial load and reduced alpha diversity. Microbial dysbiosis did not affect peristalsis at baseline but blunted the ability of \u03b1<jats:sub>2<\/jats:sub> agonists to inhibit peristalsis, while the anti\u2010peristaltic effects of sufentanil, midazolam, neostigmine and propofol were inconsistently affected. These functional alterations were complemented by a decreased expression of \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptors, toll\u2010like receptors (TRL) 3, 4 &amp; 7, IFN\u2010\u03b3 and iNOS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>Antibiotic\u2010induced decrease of bacterial load in the small intestine selectively blunts the ability of \u03b1<jats:sub>2<\/jats:sub> agonists to impair peristalsis. This effect is explained by decreased \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor expression, which may arise from TLR down\u2010regulation in the dysbiotic gut.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.70001","type":"journal-article","created":{"date-parts":[[2025,2,23]],"date-time":"2025-02-23T22:54:51Z","timestamp":1740351291000},"page":"2642-2661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Antibiotic\u2010induced decrease of bacterial load in guinea pig intestine reduces \u03b1<sub>2<\/sub>\u2010adrenoceptor expression and activity in peristaltic motor inhibition"],"prefix":"10.1111","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9606-3871","authenticated-orcid":false,"given":"Aitak","family":"Farzi","sequence":"first","affiliation":[{"name":"Division of Pharmacology, Otto Loewi Research Center Medical University of Graz  Graz 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and Intensive Care Medicine Medical University of Graz  Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5754-395X","authenticated-orcid":false,"given":"Peter","family":"Holzer","sequence":"additional","affiliation":[{"name":"Division of Pharmacology, Otto Loewi Research Center Medical University of Graz  Graz 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