Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1146978 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR30206109_1.fastq.gz | Fastqsanger.gz | |||
| SRR30206109_2.fastq.gz | Fastqsanger.gz | |||
| SRR30206110_1.fastq.gz | Fastqsanger.gz | |||
| SRR30206110_2.fastq.gz | Fastqsanger.gz | |||
| SRR30206111_1.fastq.gz | Fastqsanger.gz |
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Project description:Opioids such as morphine have many beneficial properties as analgesics, however, opioids may induce multiple adverse gastrointestinal symptoms. We have recently demonstrated that morphine treatment results in significant disruption in gut barrier function leading to increased translocation of gut commensal bacteria. However, it is unclear how opioids modulate the gut homeostasis. By using a mouse model of morphine treatment, we studied effects of morphine treatment on gut microbiome. We characterized phylogenetic profiles of gut microbes, and found a significant shift in the gut microbiome and increase of pathogenic bacteria following morphine treatment when compared to placebo. In the present study, wild type mice (C57BL/6J) were implanted with placebo, morphine pellets subcutaneously. Fecal matter were taken for bacterial 16s rDNA sequencing analysis at day 3 post treatment. A scatter plot based on an unweighted UniFrac distance matrics obtained from the sequences at OTU level with 97% similarity showed a distinct clustering of the community composition between the morphine and placebo treated groups. By using the chao1 index to evaluate alpha diversity (that is diversity within a group) and using unweighted UniFrac distance to evaluate beta diversity (that is diversity between groups, comparing microbial community based on compositional structures), we found that morphine treatment results in a significant decrease in alpha diversity and shift in fecal microbiome at day 3 post treatment compared to placebo treatment. Taxonomical analysis showed that morphine treatment results in a significant increase of potential pathogenic bacteria. Our study shed light on effects of morphine on the gut microbiome, and its role in the gut homeostasis.
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Project description:Abstract: Many mouse models of neurological disease use the tetracycline transactivator (tTA) system to control transgene expression by oral treatment with the broad-spectrum antibiotic doxycycline. Antibiotic treatment used for transgene control might have undesirable systemic effects, including the potential to affect immune responses in the brain via changes in the gut microbiome. Recent work has shown that an antibiotic cocktail to perturb the gut microbiome can suppress microglial reactivity to brain amyloidosis in transgenic mouse models of Alzheimer's disease based on controlled overexpression of the amyloid precursor protein (APP). Here we assessed the impact of chronic low dose doxycycline on gut microbiome diversity and neuroimmune response to systemic LPS challenge in a tTA-regulated model of Alzheimer's amyloidosis. We show that doxycycline decreased microbiome diversity in both APP transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite this change in microbiome composition, dox treatment had minimal effect on transcriptional signatures in the brain, both at baseline and following acute LPS challenge. Our findings suggest that central neuroinflammatory responses may be less affected by dox at doses needed for transgene control than by antibiotic cocktail at doses used for microbiome manipulation.
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