Influence of antibiotic-associated disorders of gut microbiota on cognitive function. Experimental study

Objective. To study the influence of antibiotic-associated disorders of gut microbiota on cognitive functions using an experimental biological model. Materials and methods. An experimental study was carried out using a biological model (Wistar rats, 80 animals, males of the same age). During the experiment, dysbiosis caused by the antibacterial drugs amoxicillin (Chemopharm, Serbia) and metronidazole (OOO "Ozon", Russia), injected into animals per os in subtherapeutic (1:100 of therapeutic doses) and therapeutic doses were simulated. The course of antibacterial therapy was 3 days. Microbiological examination of the biomaterial was carried out using traditional microbiological methods before and after the injection of antibacterial drugs. To assess the intensity of dysbiotic changes we used Colonization Resistance Index by Ploskireva A. A. (CRI). Neurobehavioral reactions were assessed using automated cameras (Columbus Instruments, USA) with activity analyzers (Opto-Varimex-5 Auto-Track, USA) of motor and research components, followed by automated software post-processing. Cognitive functions of the animals were examined before injection of antibacterial drugs and after the finished course. Statistical analysis of the data was performed using standard methods of descriptive statistics using "Microsoft Office Excel 2010" program. Statistical significance of the differences in the compared indices was assessed using Student's t-test at a significance level of p < 0.05 (t> 2). Results. Injection of antibiotics in animals decreased CRI at both subtherapeutic and therapeutic doses of drugs, indicating the development of microbiota disorders. When subtherapeutic doses of antibiotics were injected there was a decrease in the CRI from 0,48 (value before drug administration) to -1,86 (p<0,01) on the 3rd day after administration of the drug, which was associated with a decrease in the rodents' tentative-exploration activity from 34 (baseline value) to 11 (p<0,01). In the group of animals that received therapeutic doses of antibiotics, the CRI decreased from 0.37 to -2.34 (p<0.01) on the 3rd day of the experiment, which was also associated with a 2-fold decrease in the level of orientational research activity of rodents as compared with the background values, from 34 to 15 (p<0.01). Similar patterns were obtained about the relationship between the CRI and the motor activity of the animals on the parameter of the distance traveled. The action of subtherapeutic doses of antibiotics contributed to a decrease in the CRI, against which there was a 3-fold decrease in motor activity on the parameter of the distance traveled, from 1352 to 457 (p<0,01) on the 4th day of the experiment. Injection of therapeutic doses of antibiotics was associated with a decrease in motor activity on the parameter of the pathway from 930 to 563 (p<0.01) in the period immediately after antibiotic therapy. The changes in short-term memory in the rats were not detected. Conclusion. The effect of antibiotic-associated disorders of gut microbiota on cognitive functions of experimental animals was demonstrated objectively on the example of an experimental biological model. The severity of cognitive function decrease was in correlation with the degree of antibiotic-associated disorders of microbiota and depended on the dose of antibacterial drugs.

antibiotic-associated dysbiosis, cognitive disorders

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