Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Engertsberger, L.
Dysbiose, Darmbarrierestörung und Inflammation bei Demenz
Humanmedizin; [ Diplomarbeit/Master Thesis (UNI) ] Medizinische Universität Graz; 2022. pp.126.
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- Autor*innen der Med Uni Graz:
- Engertsberger Lara
- Betreuer*innen:
- Horvath Angela
- Stadlbauer-Köllner Vanessa
- Altmetrics:
- Abstract:
- Background: Dementia is an increasing public health threat worldwide. The pathogenesis of dementia has not been fully elucidated yet. Inflammatory processes are hypothesized to play an important role as a driver for cognitive decline but the origin of inflammation is not clear. We hypothesize that disturbances in gut microbiome composition resulting in gut barrier dysfunction and bacterial translocation to systemic circulation and, further, the brain cause an inflammatory response and are associated with cognitive dysfunction in dementia. Methods: To test this hypothesis, a cohort of 23 patients with dementia and 18 age and sex matched controls without cognitive impairments were studied. Gut microbiome composition, gut barrier dysfunction, bacterial translocation, and inflammation were assessed from stool and serum samples. Malnutrition was assessed by Mini Nutritional Assessment Short Form (MNA-SF), additionally, detailed information on drug use was collected. Microbiome composition was assessed by 16S sequencing, QIIME 2, and Calypso 7.14 tools. Results: Dementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Potentially butyrate producing bacteria, including Eubacterium rectale and members of the Lachnospiraceae genus, were less abundant in demented individuals. Gut permeability was increased as evidenced by increased serum diamine oxidase levels, and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). In a multivariate model, changes in microbiome composition of dementia patients could be explained by body mass index (BMI) and statin use. Notably, demented individuals took three times more prescription drugs than control, and three quarters of this group were malnourished. Conclusion: Dementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Demented individuals harbored less potentially butyrate producing bacteria, further promoting butyrate as a link between dysbiosis, gut barrier dysfunction, and cognitive decline. Moreover, malnutrition and drug intake were factors impacting microbiome composition. Taken together, increasing butyrate producing bacteria and targeting malnutrition may present promising therapeutic targets in dementia.