Introduction: Research has shown that the gut microbiome affects memory processes. Different antibiotic treatments lead to changes in the intestine microbiota and the dysbiosis caused by it is associated with changes in brain behavior. This study examined the effect of azithromycin on the intestine microbiome, oxidative stress, and memory in male Wistar rats. Material and methods: Two groups of adult male rats were established (n=16). In both groups, the first collection of the feces samples was done on the first day to identify the gut microbiome, then the animals were gavaged with normal saline or azithromycin (15 mg) in a volume of 1 ml daily for seven days. At the end of treatment, The second phase of collecting feces samples was completed. Then locomotion activity, novel object recognition test, Passive avoidance test, hippocampal neurons count and oxidative stress measurement in blood serum were performed. Results: Azithromycin treatment induced a significant decrease in the number of aerobic and anaerobic colonies and led to the elimination of Enterococcus faecalis and Lactobacillus acidophilus species in the experimental group intestine. Azithromycin significantly decreased memory function, number of hippocampal healthy neurons, total antioxidant capacity, superoxide dismutase, and catalase enzymes and significantly increased the amount of malondialdehyde in blood serum compared to the control group. Conclusion: In this research, azithromycin by disrupting the intestinal microbiome, reduces diversity and suppresses some bacteria, raises levels of oxidative agents in blood serum, and by reducing the number of hippocampus-healthy neurons decrease cognitive functions.
