Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Farzi, A; Tatzl, E; Kashofer, K; Trajanoski, S; Herbert, MK; Holzer, P.
Antibiotic-induced decrease of bacterial load in guinea pig intestine reduces α2-adrenoceptor expression and activity in peristaltic motor inhibition.
Br J Pharmacol. 2025;
Doi: 10.1111/bph.70001
Web of Science
PubMed
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- Führende Autor*innen der Med Uni Graz
- Farzi Aitak
- Holzer Peter
- Co-Autor*innen der Med Uni Graz
- Herbert Michael K.
- Kashofer Karl
- Tatzl Eva
- Trajanoski Slave
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- Abstract:
- BACKGROUND AND PURPOSE: 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. EXPERIMENTAL APPROACH: Guinea pigs were enorally (within the mouth) pretreated with meropenem, neomycin and vancomycin, and antibiotic-induced 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-linked immunosorbent assay [ELISA]) level. KEY RESULTS: 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 α2 agonists to inhibit peristalsis, while the anti-peristaltic effects of sufentanil, midazolam, neostigmine and propofol were inconsistently affected. These functional alterations were complemented by a decreased expression of α2-adrenoceptors, toll-like receptors (TRL) 3, 4 & 7, IFN-γ and iNOS. CONCLUSION AND IMPLICATIONS: Antibiotic-induced decrease of bacterial load in the small intestine selectively blunts the ability of α2 agonists to impair peristalsis. This effect is explained by decreased α2-adrenoceptor expression, which may arise from TLR down-regulation in the dysbiotic gut.
- Find related publications in this database (Keywords)
- antibiotics
- enteric nervous system
- intestinal peristalsis
- microbial dysbiosis
- toll-like receptors
- alpha(2)-adrenoceptors