Antibiotic-induced decrease of bacterial load in guinea pig intestine reduces α₂-adrenoceptor expression and activity...

Area of Science:

• Gastroenterology and Pharmacology
• Microbiome Research
• Critical Care Medicine

Background:

• Analgosedatives can impair gastrointestinal (GI) motility in critically ill patients, potentially leading to sepsis.
• The gut microbiota influences GI motility, but its role in analgosedative-induced peristalsis impairment is unclear.
• This study investigates how antibiotic-induced gut dysbiosis affects GI peristalsis impairment by analgosedatives.

Purpose of the Study:

• To determine if microbial dysbiosis modifies the impairment of GI peristalsis by analgosedative drugs.
• To investigate the impact of antibiotic-induced reduction in bacterial load on small intestinal peristalsis in guinea pigs.

Main Methods:

• Guinea pigs received oral antibiotics (meropenem, neomycin, vancomycin) to induce gut dysbiosis.
• Bacterial load reduction was confirmed using 16S rDNA sequencing.
• Peristalsis in isolated small intestines was assessed by measuring the pressure threshold for wave triggering.
• Gene and protein expression of key signaling molecules (e.g., adrenoceptors, toll-like receptors) was analyzed.

Main Results:

• Antibiotic treatment significantly altered the small intestinal microbiome, reducing bacterial load and alpha diversity.
• Microbial dysbiosis did not affect baseline peristalsis but blunted the inhibitory effects of alpha-2 agonists.
• The expression of alpha-2 adrenoceptors, toll-like receptors (TLR 3, 4, 7), IFN-γ, and iNOS was decreased.

Conclusions:

• Antibiotic-induced gut bacterial reduction selectively impairs the ability of alpha-2 agonists to inhibit intestinal peristalsis.
• This functional change is attributed to decreased alpha-2 adrenoceptor expression.
• Down-regulation of TLRs in the dysbiotic gut may contribute to the observed decrease in alpha-2 adrenoceptor expression.