Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Stojanovic, N.
Establishment of a novel antibiotics model to study microbiota-gut-brain axis signaling in zebrafish.
[ Diplomarbeit/Master Thesis (UNI) ] Universität Graz; 2024.
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- Autor*innen der Med Uni Graz:
- Betreuer*innen:
- Reichmann Florian
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- Abstract:
- The bidirectional communication between gut microbiota and the brain is essential for proper brain function and gut homeostasis. Gut microbiota induce neurochemical alterations and influence behavioral patterns via gut-brain signaling. Although the molecular mechanisms by which gut microbiota influence brain areas important for behavior are not completely understood, it appears that the neurotransmitters serotonin and histamine play an essential role in mediating gut-brain signaling. The aim of this study was, therefore, to establish a novel antibiotics model in zebrafish larvae to evaluate the impact of microbiota composition on locomotor and anxiety-like behavior as well as the serotonergic and histaminergic system. For this purpose, zebrafish larvae at 3 days post fertilization were exposed to different concentrations of vancomycin, meropenem or combinations thereof to deplete the gut microbiota early in life. Treatment effects on microbiota composition were evaluated by 16S rRNA sequencing and effects on locomotor and anxiety-like behavior were analyzed using a video-tracking software. Additionally, antibiotic treatment effects on gene expression of transcripts involved in serotonin and histamine metabolism in the brain were evaluated by quantitative real-time PCR. Antibiotic treatment for 48h significantly altered microbiota composition and increased alpha and beta diversity. In addition, bacterial load was significantly reduced after meropenem and antibiotic combination treatment. The behavioral analysis revealed increased immobility of larvae treated with 1µM meropenem, which indicates heightened anxiety-like behavior. Interestingly, however, treatment with vancomycin or vancomycin and meropenem in combination didn’t influence anxiety-like behavior and locomotor activity. At the molecular level, the vancomycin treatment induced a substantial increase in the gene expression of serotonin synthesizing enzymes (tph1a, tph2), the serotonin degrading enzyme in zebrafish (mao), and serotonin transporters (slc6a4a, slc6a4b). In contrast, no differences were observed in the histaminergic system upon antibiotic treatment. These findings indicate that alterations in the microbiota composition can affect anxiety-like behavior and locomotor activity and influence serotonin metabolism in the brain.