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The antidepressant Amitriptyline induces gut microbiome dysbiosis and facilitates enteropathogenic infection in mice
Amitriptyline is a tricyclic antidepressant that has been used in the clinics to mainly treat depression, but also other conditions, such as chronic pain, insomnia and irritable bowel syndrome. It has been shown that amitriptyline exerts multiple functions, including the inhibition of the acid sphingomyelinase, as well as exhibiting antiinflammatory and antimicrobial properties. Patients with depression are prone to infections but it remains poorly understood, if there is a direct correlation to drug intake. Interestingly, amitriptyline-treated mice are highly susceptible to an enteropathogenic infection. Considering the significance of a balanced microbial homeostasis in providing protection against infections, the present study hypothesized that a potential antimicrobial activity of amitriptyline might contribute to the increased susceptibility to enteropathogenic Citrobacter rodentium infection. Therefore, this study aimed to examine the effect of amitriptyline on the gut microbiota of Citrobacter rodentium infected mice and its impact on the gut microbiome under homeostatic conditions. Using 16S rRNA gene sequencing, it was found that oral amitriptyline treatment significantly reduced gut microbial diversity and substantially altered the microbial composition during infection and under homeostatic conditions. Moreover, there was a notable decrease in butyrate-producing bacteria after amitriptyline treatment, which was consistent with reduced butyrate levels in the feces of amitriptyline-treated mice. Analysis of T lymphocytes in the colon revealed a significant decrease in the frequency of regulatory T cells and an overall reduction in the secretion of pro- and antiinflammatory cytokines in specific pathogen-free mice, but not in germ-free mice. Thus, these findings provide robust evidence for the direct influence of amitriptyline in the cross-talk between the host and the gut microbiota. In conclusion, this study offers new insights into the importance of an amitriptyline-mediated microbial shift for ...
The antidepressant Amitriptyline induces gut microbiome dysbiosis and facilitates enteropathogenic infection in mice
Amitriptyline is a tricyclic antidepressant that has been used in the clinics to mainly treat depression, but also other conditions, such as chronic pain, insomnia and irritable bowel syndrome. It has been shown that amitriptyline exerts multiple functions, including the inhibition of the acid sphingomyelinase, as well as exhibiting antiinflammatory and antimicrobial properties. Patients with depression are prone to infections but it remains poorly understood, if there is a direct correlation to drug intake. Interestingly, amitriptyline-treated mice are highly susceptible to an enteropathogenic infection. Considering the significance of a balanced microbial homeostasis in providing protection against infections, the present study hypothesized that a potential antimicrobial activity of amitriptyline might contribute to the increased susceptibility to enteropathogenic Citrobacter rodentium infection. Therefore, this study aimed to examine the effect of amitriptyline on the gut microbiota of Citrobacter rodentium infected mice and its impact on the gut microbiome under homeostatic conditions. Using 16S rRNA gene sequencing, it was found that oral amitriptyline treatment significantly reduced gut microbial diversity and substantially altered the microbial composition during infection and under homeostatic conditions. Moreover, there was a notable decrease in butyrate-producing bacteria after amitriptyline treatment, which was consistent with reduced butyrate levels in the feces of amitriptyline-treated mice. Analysis of T lymphocytes in the colon revealed a significant decrease in the frequency of regulatory T cells and an overall reduction in the secretion of pro- and antiinflammatory cytokines in specific pathogen-free mice, but not in germ-free mice. Thus, these findings provide robust evidence for the direct influence of amitriptyline in the cross-talk between the host and the gut microbiota. In conclusion, this study offers new insights into the importance of an amitriptyline-mediated microbial shift for ...
The antidepressant Amitriptyline induces gut microbiome dysbiosis and facilitates enteropathogenic infection in mice
Lange, Erik (Autor:in) / Westendorf, Astrid
19.09.2023
Hochschulschrift
Elektronische Ressource
Englisch
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