Journal of Sciences, Islamic Republic of Iran

Current Issue

By Issue

By Author

By Subject

Author Index

Keyword Index

About Journal

Aims and Scope

Editorial Board

Publication Ethics

Indexing and Abstracting

Related Links

FAQ

Peer Review Process

Journal Metrics

News

Azithromycin Therapy Changed the Intestinal Microbiota, Caused Oxidative Stress, and Decreased Memory Function in Adult Wistar Rats

Document Type : Original Paper

Authors

Department of Biology, Faculty of Sciencse, Arak University, Arak, 384817758, Islamic Republic of Iran

Abstract

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. 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. 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. 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 decreases cognitive functions.

Keywords

Main Subjects

References
  1. Crane AL, Helton EJ, Ferrari MC, Mathis A. Learning to find food: evidence for embryonic sensitization and juvenile social learning in a salamander. Animal Behaviour. 2018;142:199-206.
  2. Britannica E. Available online: https://www. britannica. com/science. Geophone (accessed on 10 March 2021.
  3. Lee AR, Kim JH, Cho E, Kim M, Park M. Dorsal and ventral hippocampus differentiate in functional pathways and differentially associate with neurological disease-related genes during postnatal development. Frontiers in molecular neuroscience. 2017;10:331.
  4. Dupont HL, Jiang Z-D, Dupont AW, Utay NS. The intestinal microbiome in human health and disease. Transactions of the American Clinical and Climatological Association. 2020;131:178.
  5. Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek. 2020;113(12):2019-40.
  6. Ortigão R, Pimentel-Nunes P, Dinis-Ribeiro M, Libânio D. Gastrointestinal microbiome–what we need to know in clinical practice. GE-Portuguese Journal of Gastroenterology. 2020;27(5):336-51.
  7. Angoorani P, Hasani-Ranjbar S, Soroush AR, Siadat SD, Ejtahed HS, Sharifi F, et al. The role of intestinal Microbiota in cognitive disorders. Journal of Mazandaran University of Medical Sciences. 2021;30(193):113-24.
  8. Tang W, Meng Z, Li N, Liu Y, Li L, Chen D, Yang Y. Roles of gut microbiota in the regulation of hippocampal plasticity, inflammation, and hippocampus-dependent behaviors. Frontiers in cellular and infection microbiology. 2021;10:611014.
  9. Lou H, Wang J, Wang Y, Gao Y, Wang W. Comprehensive assessment of Enterococcus faecalis SN21-3: Probiotic features and safety evaluation for potential animal use. Food Bioscience. 2024;58:103688.
  10. Neufeld NH, Mohamed NS, Grujich N, Shulman K. Acute neuropsychiatric symptoms associated with antibiotic treatment of Helicobacter pylori infections: a review. Journal of Psychiatric Practice. 2017;23(1):25-35.
  11. Chams N, Chams S, Badran R, Shams A, Araji A, Raad M, et al. COVID-19: a multidisciplinary review. Frontiers in public health. 2020;8:383.
  12. Parnham MJ, Haber VE, Giamarellos-Bourboulis EJ, Perletti G, Verleden GM, Vos R. Azithromycin: mechanisms of action and their relevance for clinical applications. Pharmacology & therapeutics. 2014;143(2):225-45.
  13. Echeverría-Esnal D, Martin-Ontiyuelo C, Navarrete-Rouco ME, De-Antonio Cuscó M, Ferrández O, Horcajada JP, Grau S. Azithromycin in the treatment of COVID-19: a review. Expert review of anti-infective therapy. 2021;19(2):147-63.
  14. Singh Y, Trautwein C, Romani J, Salker MS, Neckel PH, Fraccaroli I, et al. Overexpression of human alpha-Synuclein leads to dysregulated microbiome/metabolites with ageing in a rat model of Parkinson disease. Molecular Neurodegeneration. 2023;18(1):44.
  15. Mahgoub A, El-Medany A, Mustafa A, Arafah M, Moursi M. Azithromycin and erythromycin ameliorate the extent of colonic damage induced by acetic acid in rats. Toxicology and applied pharmacology. 2005;205(1):43-52.
  16. Komijani M, Bouzari M, Rahimi F. Detection and characterization of a novel lytic bacteriophage (vB-KpneM-Isf48) against Klebsiella pneumoniae isolates from infected wounds carrying antibiotic-resistance genes (TEM, SHV, and CTX-M). 2017.
  17. Reynolds J. Serial dilution protocols. American Society for Microbiology: Washington, DC, USA. 2005:1-7.
  18. Dutka-Malen S, Evers S, Courvalin P. Detection of glycopeptide resistance genotypes and identification to the species level of clinically relevant enterococci by PCR. Journal of clinical microbiology. 1995;33(1):24-7.
  19. You I, Kim EB. Genome-based species-specific primers for rapid identification of six species of Lactobacillus acidophilus group using multiplex PCR. PloS one. 2020;15(3):e0230550.
  20. Parvin MS, Talukder S, Ali MY, Chowdhury EH, Rahman MT, Islam MT. Antimicrobial resistance pattern of Escherichia coli isolated from frozen chicken meat in Bangladesh. Pathogens. 2020;9(6):420.
  21. Darbandi N, Komijani M, Tajiani Z. New findings about comparing the effects of antibiotic therapy and phage therapy on memory and hippocampal pyramidal cells in rats. Journal of Clinical Laboratory Analysis. 2023;37(11-12):e24942.
  22. Griffin SM, Lehtinen MJ, Meunier J, Ceolin L, Roman FJ, Patterson E. Restorative effects of probiotics on memory impairment in sleep-deprived mice. Nutritional Neuroscience. 2023;26(3):254-64.
  23. Darbandi N, Ramezani M, Noori M. Mespilus germanica Flavonoids Attenuate Cognitive Dysfunction in the Streptozotocin-induced Rat Model of Alzheimer's Disease. Indian Journal of Pharmaceutical Sciences. 2018;80(4).
  24. Darbandi N, Momeni H. Effect of zinc oxide nanoparticles on memory retrieval, hippocampal CA1 pyramidal neurons and some serum oxidative stress factors in male wistar rats. Studies in Medical Sciences. 2018;29(6):450-63.
  25. Buege, J. A. Microsomal lipid peroxidation. Methods in enzymology, (1978); 52, 302-310.
  26. Benzie, I. F., & Strain, J. J. The ferric reducing ability of plasma (FRAP) as a measure of “antioxidant power”: the FRAP assay. Analytical biochemistry, (1996); 239(1), 70-76.
  27. Marklund, S., & Marklund, G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. European journal of biochemistry, (1974); 47(3), 469-474.
  28. Aebi, H. Catalase in vitro. In Methods in enzymology. Elsevier (1984); Vol. 105, pp. 121-126.
  29. Pennycook JH, Scanlan PD. Ecological and evolutionary responses to antibiotic treatment in the human gut microbiota. FEMS Microbiology Reviews. 2021;45(5):fuab018.
  30. Nikolaou E, Kamilari E, Savkov D, Sergeev A, Zakharova I, Vogazianos P, et al. Intestinal microbiome analysis demonstrates azithromycin post-treatment effects improve when combined with lactulose. World Journal of Pediatrics. 2020;16:168-76.
  31. Stegarescu A, Lung I, Ciorîță A, Kacso I, Opriș O, Soran M-L, Soran A. The Antibacterial Properties of Nanocomposites Based on Carbon Nanotubes and Metal Oxides Functionalized with Azithromycin and Ciprofloxacin. Nanomaterials. 2022;12(23):4115.
  32. Banerjee A, Pal S, Goswami P, Batabyal K, Joardar SN, Dey S, et al. Docking analysis of circulating CTX-M variants in multi-drug resistant, beta-lactamase and biofilm-producing E. coli isolated from pet animals and backyard livestock. Microbial Pathogenesis. 2022;170:105700.
  33. Getanda P, Bojang A, Camara B, Jagne-Cox I, Usuf E, Howden BP, et al. Short-term increase in the carriage of azithromycin-resistant Escherichia coli and Klebsiella pneumoniae in mothers and their newborns following intra-partum azithromycin: a post hoc analysis of a double-blind randomized trial. JAC-antimicrobial resistance. 2021;3(1):dlaa128.
  34. Jiang S, Li T, Zhou X, Qin W, Wang Z, Liao Y. Antibiotic drug piperacillin induces neuron cell death through mitochondrial dysfunction and oxidative damage. Canadian Journal of Physiology and Pharmacology. 2018;96(6):562-8.
  35. Heidary M, Ebrahimi Samangani A, Kargari A, Kiani Nejad A, Yashmi I, Motahar M, et al. Mechanism of action, resistance, synergism, and clinical implications of azithromycin. Journal of Clinical Laboratory Analysis. 2022;36(6):e24427.
  36. Roe K. An alternative explanation for Alzheimer’s disease and Parkinson’s disease initiation from specific antibiotics, gut microbiota dysbiosis and neurotoxins. Neurochemical Research. 2022;47(3):517-30.
  37. Mehta RS, Lochhead P, Wang Y, Ma W, Nguyen LH, Kochar B, et al. Association of midlife antibiotic use with subsequent cognitive function in women. Plos one. 2022;17(3):e0264649.

 
  1. Li J, Pu F, Peng C, Wang Y, Zhang Y, Wu S, et al. Antibiotic cocktail-induced gut microbiota depletion in different stages could cause host cognitive impairment and emotional disorders in adulthood in different manners. Neurobiology of Disease. 2022;170:105757.
  2. Ahmed M, Roy S, Iktidar MA, Chowdhury S, Akter S, Islam AK, Hawlader MDH. Post-COVID-19 memory complaints: prevalence and associated factors. Neurologia. 2022.
  3. Ferreira-Junior AS, Borgonovi TF, De Salis LVV, Leite AZ, Dantas AS, De Salis GVV, et al. Detection of intestinal dysbiosis in post-COVID-19 patients one to eight months after acute disease resolution. International journal of environmental research and public health. 2022;19(16):10189.
  4. Dai C, Xiao X, Zhang Y, Xiang B, Hoyer D, Shen J, et al. Curcumin attenuates colistin-induced peripheral neurotoxicity in mice. ACS Infectious Diseases. 2020;6(4):715-24.
  5. Darwish B, Chamaa F, Awada B, Lawand N, Saadé NE, Abou Fayad AG, Abou-Kheir W. Urinary Tract Infections Impair Adult Hippocampal Neurogenesis. Biology. 2022;11(6):891.
  6. Megur A, Baltriukienė D, Bukelskienė V, Burokas A. The microbiota–gut–brain axis and Alzheimer’s disease: neuroinflammation is to blame? Nutrients. 2020;13(1):37.
  7. Hao W-Z, Li X-J, Zhang P-W, Chen J-X. A review of antibiotics, depression, and the gut microbiome. Psychiatry research. 2020;284:112691.
  8. Silva YP, Bernardi A, Frozza RL. The role of short-chain fatty acids from gut microbiota in gut-brain communication. Frontiers in endocrinology. 2020;11:25.
  9. Lee L-H, Ser H-L, Khan TM, Long M, Chan K-G, Goh B-H, Ab Mutalib N-S. IDDF2018-ABS-0239 Dissecting the gut and brain: potential links between gut microbiota in development of alzheimer’s disease? : BMJ Publishing Group; 2018.
  10. Cuesta CM, Guerri C, Ureña J, Pascual M. Role of microbiota-derived extracellular vesicles in gut-brain communication. International Journal of Molecular Sciences. 2021;22(8):4235.
  11. Jara C, Torres AK, Olesen MA, Tapia-Rojas C. Mitochondrial dysfunction as a key event during aging: from synaptic failure to memory loss. Mitochondria and Brain disorders. 2019.
  12. Kalghatgi S, Spina CS, Costello JC, Liesa M, Morones-Ramirez JR, Slomovic S, et al. Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in mammalian cells. Science translational medicine. 2013;5(192):192ra85-ra85.
  13. Lleonart ME, Grodzicki R, Graifer DM, Lyakhovich A. Mitochondrial dysfunction and potential anticancer therapy. Medicinal Research Reviews. 2017;37(6):1275-98.
Journal of Sciences, Islamic Republic of Iran
Volume 35, Issue 1
March 2024
Pages 5-14
Files
Share
How to cite
Statistics