Abstract
BackgroundDementia 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, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia.MethodsTo 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), detailed information on drug use was collected. Microbiome composition was assessed by 16S rRNA sequencing, QIIME 2 and Calypso 7.14 tools.ResultsDementia was associated with dysbiosis characterized by differences in beta diversity and changes in taxonomic composition. Gut permeability was increased as evidenced by increased serum diamine oxidase (DAO) levels and systemic inflammation was confirmed by increased soluble cluster of differentiation 14 levels (sCD14). BMI and statin use had the strongest impact on microbiome composition.ConclusionDementia is associated with changes in gut microbiome composition and increased biomarkers of gut permeability and inflammation. Lachnospiraceae NK4A136 group as potential butyrate producer was reduced in dementia. Malnutrition and drug intake were factors, that impact on microbiome composition. Increasing butyrate producing bacteria and targeting malnutrition may be promising therapeutic targets in dementia.Trial registrationNCT03167983.
Highlights
Dementia is an increasing public health threat worldwide
We hypothesize that dementia is associated with dysbiosis, gut barrier dysfunction and inflammation and we aim to identify external factors influencing microbiome composition in dementia, such as nutrition and drug intake
From 2 dementia patients we were not able to collect enough stool and blood samples to do the intended analyses; they were excluded from the final analysis. (Fig. 1) Dementia patients had a lower body mass index (BMI) and erythrocyte count as well as lower serum albumin and total protein levels compared to controls
Summary
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, gut barrier dysfunction, bacterial translocation and resulting inflammation are associated with cognitive dysfunction in dementia. Inflammation is further associated with an increase in gut permeability, mucosal inflammation and bacterial translocation [2]. Animal studies suggest that AD is associated with changes in the gut microbiome composition with a decrease in beneficial, anti-inflammatory genera [7]. A study from Japan has shown that gut microbiome composition is independently and strongly associated with dementia [10]. It has been recently published that the microbiome of dementia patients causes a dysregulation of the anti-inflammatory P-glycoprotein pathway [11]
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