A301 GUT MICROBIOTA FROM A PATIENT WITH GENERALIZED ANXIETY DISORDER INDUCES ANXIETY-LIKE BEHAVIOUR AND ALTERED BRAIN CHEMISTRY IN GNOTOBIOTIC MICE
| Autor: | Elena F. Verdu, Michael G. Surette, M Amber, Stephen M. Collins, E Perez Guzman, G De Palma, Randi E. McCabe, Rebecca Anglin, Jun Lu, Ryan Potts, P Bercik |
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| Rok vydání: | 2018 |
| Předmět: |
Brain-derived neurotrophic factor
Generalized anxiety disorder biology business.industry Gut flora medicine.disease biology.organism_classification digestive system Amygdala Pathophysiology Poster Presentations medicine.anatomical_structure Immunology medicine Anxiety Microbiome medicine.symptom business Depression (differential diagnoses) |
| Zdroj: | Journal of the Canadian Association of Gastroenterology. 1:523-524 |
| ISSN: | 2515-2092 2515-2084 |
| DOI: | 10.1093/jcag/gwy008.302 |
| Popis: | BACKGROUND: Depression and anxiety have overlapping etiologies and their pathophysiology remains largely unknown. Accumulating data suggest that gut microbiota modulates brain function and behaviour and may play a role in the pathophysiology of depression and anxiety AIMS: To investigate whether gut microbiota from patients with Generalized Anxiety Disorder (GAD) induces anxiety-like behaviour in gnotobiotic mice and whether this is accompanied by changes in brain chemistry and immune markers. METHODS: Germ-free NIH Swiss mice (n=15) were colonized with microbiota from either a patient with GAD and history of depression (n=7) or from an age and sex-matched healthy control (HC) (n=8). Both the GAD patient (female, 19 years) and healthy control (female, 20 years) were well characterized and selected based on their Depression, Anxiety, and Stress Scale (DASS) scores from a pool of participants of an ongoing clinical study. Three weeks post-colonization, the mice underwent behavioural assessment using standard psychometric tests. Stool β-defensin levels were measured by ELISA. Microbiota profiles were assessed by 16S rRNA based Illumina analysis. Lastly, BDNF expression in brain samples was measured by immunofluorescence and neural gene expression by Nanostring gene assay. RESULTS: GAD-colonized mice had a distinct microbiota profile from that of HC-colonized mice and each group clustered around their respective human donor. Fecal β-defensin levels were higher in the GAD patient than the HC (109.5ng/ml vs 18.01ng/ml). Similarly, mouse fecal β-defensin levels were significantly higher in GAD-colonized mice than in HC-colonized mice (M= 62.26 vs M= 29.10, p < 0.005). Mice colonized with GAD microbiota exhibited significantly greater anxiety and depressive-like behaviour than HC-colonized mice, as they spent less time in the center of the open field arena, buried a greater number of marbles, spent a greater time digging and remained more time immobile. GAD-colonized mice had increased BDNF expression in the amygdala but decreased expression in the hippocampus. GAD-colonized mice also exhibited differential expression of neural genes in both the amygdala and hippocampus. CONCLUSIONS: Our results suggest that GAD microbiota can induce anxiety and depressive-like behaviour, accompanied by elevated immune markers. This is associated with altered neural gene and BDNF expression in brain regions involved in emotional processing. Altogether, our data suggest that gut microbiota may contribute to the pathophysiology of anxiety and depression, at least in a subset of patients with signs of gut immune activation. These findings may lead to the development of novel biomarkers and treatments for mood disorders. FUNDING AGENCIES: CIHRNIH |
| Databáze: | OpenAIRE |
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