From: deputyfife23x@gmail.com   
      
   Interplay of the microbiome and the brain in neurodegenerative disease    
   Bonini, Nancy M.        
   University of Pennsylvania, Philadelphia, PA, United States   
     Abstract    
   One of most unexpected and surprising recent areas of scientific investigation   
   are interactions of the intestinal microbiome on health and disease.   
   Interesting findings include the impact of the microbiome on heart disease due   
   to metabolites generated by    
   bacterial flora promoted by meat consumption, and the impact of the microbiome   
   on obesity. The interactions between the microbiome and the host are likely   
   bidirectional, with the host state impacting the diversity and range of the   
   intestinal microbiome,    
   as well as the intestinal microbiome impacting host health and disease state.   
   Understanding these interactions and how they influence and are influenced by   
   disease is an exploding area of biology with profound implications for health.   
   However, a huge    
   challenge in this work is the difficulty and expense in performing the   
   experiments, in either humans or mammalian models like mice. Diseases,   
   especially chronic neurodegenerative diseases, are especially difficult to   
   investigate for these interactions    
   because of the advanced age of the individuals and their physical condition.   
   We propose to use Drosophila for pioneering studies to assess if the   
   microbiome is impacted by degenerative disease in the animal, and if the   
   microbiome impacts the presentation    
   of disease. Our laboratory has a special focus on amyotrophic lateral   
   sclerosis/frontotemporal dementia and Parkinson's disease, and we propose to   
   initiate studies with robust models for these disorders.    
   In Aim 1, we will assess the impact of neurodegenerative disease on the   
   microbiota of the animal. We will define the gut microbiome of animals over   
   progression of disease longitudinally in the adult, using a range of critical   
   models for these diseases.    
   These studies will define if the microbiome is altered upon disease onset or   
   progression, as well as provide a comparison of this impact between different   
   models of disease.    
   In Aim 2, we will investigate the reciprocal interaction, to determine if the   
   gut microbiome impacts progression and severity of neurodegenerative disease.   
   We will grow disease models germ free on axenic medium and assess key   
   benchmarks and features of    
   the disease phenotype. These experiments will define whether the gut   
   microbiota of the animal itself has an impact on the onset, progression or   
   severity of disease. Here we take advantage of the fact that experiments with   
   gnotobiotic flies are    
   straightforward, while experiments with gnotobiotic vertebrates are quite   
   difficult and expensive. The findings of these Aims will define the reciprocal   
   impact between the microbiome and the neurodegenerative disease state of the   
   animal, to assess these    
   inter-related connections. These studies will establish a "simple model"   
   foundation for microbiota-animal interactions in neurodegenerative disease,   
   providing predictions for more complex-but slower and far more e   
   pensive-animals.    
      
   Public Health Relevance    
      
   It is becoming well recognized that there are dramatic interactions between   
   our gut microbial flora and our health. However, systems in which these   
   interactions can be studied effectively in detail are limited. Here we propose   
   to examine the gut    
   microbiota interactions with brain disease state using the model organism   
   Drosophila~ Drosophila has proven exceptional for defining mechanistic insight   
   into human neurodegenerative disease. These studies may lead to the foundation   
   for novel therapies to    
   delay the onset or progression of disease.    
      
     Funding Agency    
   Agency    
   National Institute of Health (NIH)    
   Institute    
   National Institute of Neurological Disorders and Stroke (NINDS)    
   Type    
   Exploratory/Developmental Grants (R21) Project #    
   1R21NS088370-01 Application #    
   8755389    
   Study Section    
   Cellular and Molecular Biology of Neurodegeneration Study Section (CMND)   
   Program Officer    
   Gubitz, Amelie    
   Project Start    
   2014-05-01    
   Project End    
   2016-04-30    
   Budget Start    
   2014-05-01    
   Budget End    
   2015-04-30    
   Support Year    
   1    
   Fiscal Year    
   2014    
   Total Cost    
   $236,396    
   Indirect Cost    
   $86,396    
     Institution    
   Name    
   University of Pennsylvania Department    
   Biology    
   Type    
   Schools of Arts and Sciences    
   DUNS #    
   042250712    
   City    
   Philadelphia    
   State    
   PA    
   Country    
   United States    
   Zip Code    
   19104    
     Related projects    
   NIH 2015    
   R21 NS        Interplay of the microbiome and the brain in neurodegenerative   
   disease    
   Bonini, Nancy M. / University of Pennsylvania            
   NIH 2014    
   R21 NS        Interplay of the microbiome and the brain in neurodegenerative   
   disease    
   Bonini, Nancy M. / University of Pennsylvania        $236,396    
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