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427 Defining the Impact of the Fecal Microbiome and Secretome on Multiple System Atrophy and α-Synuclein Aggregation
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- Michelle K. Bland, Wolfgang Singer, Marina R. S. Walther-António
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- Journal:
- Journal of Clinical and Translational Science / Volume 8 / Issue s1 / April 2024
- Published online by Cambridge University Press:
- 03 April 2024, p. 127
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OBJECTIVES/GOALS: Aim 1: We will determine whether temporal changes in the fecal microbiome signature correlate with a clinical multiple system atrophy (MSA) phenotype. Aim 2: We will evaluate whether secretomes cultured from fecal samples from MSA patients enhance intracellular and extracellular α-synuclein (αSyn) aggregation using in vitro functional assays. METHODS/STUDY POPULATION: Aim 1: Gut microbiome profiling will be performed by 16S rRNA gene sequencing, tandem mass spectrometry for expression proteomics, and targeted metabolomics in fecal samples from 30 MSA cases matched to 30 healthy controls, a Parkinson’s disease comparison group, and household controls. Aim 2: Microbial species will be isolated using dilution-to-extinction on MSA fecal samples and then will be cultured to obtain secretomes. To assess the effect of MSA fecal secretomes on αSyn aggregation, culture media from microbial isolates will be used in fluorescence resonance energy transfer (FRET) assays and luciferase reporter assays, both modified to measure αSyn aggregation. Positive tests will undergo expanded metagenomic characterization of the microbes and secretome to identify potential causative agent(s). RESULTS/ANTICIPATED RESULTS: Based on cross-sectional metagenomic studies on MSA, MSA cases are expected to have genus reductions in Blautia and Dorea (acetate production); Paraprevotella (succinic and acetic acid production); and Ruminococcus, Coprococcus, and Faecalibacterium (butyrate production). Increases in genus Bacteroides (clinical pathogen) and Akkermansia (mucin degradation) and pro-inflammatory families Clostridiaceae and Rikenellaceae are also expected. MSA is predicted to be associated with reduced levels of short chain fatty acids and increased lipopolysaccharide. These microbial proteins and metabolites are anticipated to modulate intracellular and extracellular αSyn aggregation in vitro. Microbe isolation and secretome culturing methods are expected to identify additional drivers of αSyn aggregation. DISCUSSION/SIGNIFICANCE: This study’s novel use of longitudinal sampling, household controls, and secretome culturing aim to develop a more comprehensive understanding of the complex interactions between the gut microbiome and MSA. The success of this work offers the potential for new insights into the impact of the gut microbiome and secretome on MSA and αSyn aggregation.
Effectiveness of geropsychiatric home treatment concerning parameters of physical health: matched-pair study
- Christa Peinhaupt, Gernot Fassolder, Wolfgang Habacher, Monika Singer, Gerhard Hermann, Günter Klug
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- Journal:
- BJPsych Open / Volume 7 / Issue 5 / September 2021
- Published online by Cambridge University Press:
- 02 September 2021, e163
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Background
There is evidence of the effectiveness of multi-professional home treatment models with regards to improving mental health for elderly patients with mental illness. However, there is a lack of studies examining the efficacy with regard to physical health.
AimsTo explore the effectiveness of geropsychiatric home treatment for elderly patients with mental illness with regards to improving physical health by assessing the need of physical treatment.
MethodA 1-year retrospective matched-pair cohort study was conducted in four regions of Austria. We compared 91 patients with a broad spectrum of mental disorders in geropsychiatric home treatment by 1:2 matching to 182 patients in treatment as usual regarding number of contacts with health services, prescriptions, hospital discharges and length of hospital stay.
ResultsPatients in geropsychiatric home treatment showed significantly lower numbers of consultations with general practitioners (P < 0.001) and specialists (internal medicine, P = 0.022; psychiatry, P < 0.001), and lower numbers of prescriptions (medical drugs except psychotropic drugs, P < 0.001; psychotropic drugs, P < 0.004) compared with patients in treatment as usual. However, there was no significant difference in the number of hospital discharges and length of hospital stays.
ConclusionsGeropsychiatric home treatment has a positive effect on mental and physical parameters, which is discussed in the context of stress reduction.
Contributors
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- By Aakash Agarwala, Linda S. Aglio, Rae M. Allain, Paul D. Allen, Houman Amirfarzan, Yasodananda Kumar Areti, Amit Asopa, Edwin G. Avery, Patricia R. Bachiller, Angela M. Bader, Rana Badr, Sibinka Bajic, David J. Baker, Sheila R. Barnett, Rena Beckerly, Lorenzo Berra, Walter Bethune, Sascha S. Beutler, Tarun Bhalla, Edward A. Bittner, Jonathan D. Bloom, Alina V. Bodas, Lina M. Bolanos-Diaz, Ruma R. Bose, Jan Boublik, John P. Broadnax, Jason C. Brookman, Meredith R. Brooks, Roland Brusseau, Ethan O. Bryson, Linda A. Bulich, Kenji Butterfield, William R. Camann, Denise M. Chan, Theresa S. Chang, Jonathan E. Charnin, Mark Chrostowski, Fred Cobey, Adam B. Collins, Mercedes A. Concepcion, Christopher W. Connor, Bronwyn Cooper, Jeffrey B. Cooper, Martha Cordoba-Amorocho, Stephen B. Corn, Darin J. Correll, Gregory J. Crosby, Lisa J. Crossley, Deborah J. Culley, Tomas Cvrk, Michael N. D'Ambra, Michael Decker, Daniel F. Dedrick, Mark Dershwitz, Francis X. Dillon, Pradeep Dinakar, Alimorad G. Djalali, D. John Doyle, Lambertus Drop, Ian F. Dunn, Theodore E. Dushane, Sunil Eappen, Thomas Edrich, Jesse M. Ehrenfeld, Jason M. Erlich, Lucinda L. Everett, Elliott S. Farber, Khaldoun Faris, Eddy M. Feliz, Massimo Ferrigno, Richard S. Field, Michael G. Fitzsimons, Hugh L. Flanagan Jr., Vladimir Formanek, Amanda A. Fox, John A. Fox, Gyorgy Frendl, Tanja S. Frey, Samuel M. Galvagno Jr., Edward R. Garcia, Jonathan D. Gates, Cosmin Gauran, Brian J. Gelfand, Simon Gelman, Alexander C. Gerhart, Peter Gerner, Omid Ghalambor, Christopher J. Gilligan, Christian D. Gonzalez, Noah E. Gordon, William B. Gormley, Thomas J. Graetz, Wendy L. Gross, Amit Gupta, James P. Hardy, Seetharaman Hariharan, Miriam Harnett, Philip M. Hartigan, Joaquim M. Havens, Bishr Haydar, Stephen O. Heard, James L. Helstrom, David L. Hepner, McCallum R. Hoyt, Robert N. Jamison, Karinne Jervis, Stephanie B. Jones, Swaminathan Karthik, Richard M. Kaufman, Shubjeet Kaur, Lee A. Kearse Jr., John C. Keel, Scott D. Kelley, Albert H. Kim, Amy L. Kim, Grace Y. Kim, Robert J. Klickovich, Robert M. Knapp, Bhavani S. Kodali, Rahul Koka, Alina Lazar, Laura H. Leduc, Stanley Leeson, Lisa R. Leffert, Scott A. LeGrand, Patricio Leyton, J. Lance Lichtor, John Lin, Alvaro A. Macias, Karan Madan, Sohail K. Mahboobi, Devi Mahendran, Christine Mai, Sayeed Malek, S. Rao Mallampati, Thomas J. Mancuso, Ramon Martin, Matthew C. Martinez, J. A. Jeevendra Martyn, Kai Matthes, Tommaso Mauri, Mary Ellen McCann, Shannon S. McKenna, Dennis J. McNicholl, Abdel-Kader Mehio, Thor C. Milland, Tonya L. K. Miller, John D. Mitchell, K. Annette Mizuguchi, Naila Moghul, David R. Moss, Ross J. Musumeci, Naveen Nathan, Ju-Mei Ng, Liem C. Nguyen, Ervant Nishanian, Martina Nowak, Ala Nozari, Michael Nurok, Arti Ori, Rafael A. Ortega, Amy J. Ortman, David Oxman, Arvind Palanisamy, Carlo Pancaro, Lisbeth Lopez Pappas, Benjamin Parish, Samuel Park, Deborah S. Pederson, Beverly K. Philip, James H. Philip, Silvia Pivi, Stephen D. Pratt, Douglas E. Raines, Stephen L. Ratcliff, James P. Rathmell, J. Taylor Reed, Elizabeth M. Rickerson, Selwyn O. Rogers Jr., Thomas M. Romanelli, William H. Rosenblatt, Carl E. Rosow, Edgar L. Ross, J. Victor Ryckman, Mônica M. Sá Rêgo, Nicholas Sadovnikoff, Warren S. Sandberg, Annette Y. Schure, B. Scott Segal, Navil F. Sethna, Swapneel K. Shah, Shaheen F. Shaikh, Fred E. Shapiro, Torin D. Shear, Prem S. Shekar, Stanton K. Shernan, Naomi Shimizu, Douglas C. Shook, Kamal K. Sikka, Pankaj K. Sikka, David A. Silver, Jeffrey H. Silverstein, Emily A. Singer, Ken Solt, Spiro G. Spanakis, Wolfgang Steudel, Matthias Stopfkuchen-Evans, Michael P. Storey, Gary R. Strichartz, Balachundhar Subramaniam, Wariya Sukhupragarn, John Summers, Shine Sun, Eswar Sundar, Sugantha Sundar, Neelakantan Sunder, Faraz Syed, Usha B. Tedrow, Nelson L. Thaemert, George P. Topulos, Lawrence C. Tsen, Richard D. Urman, Charles A. Vacanti, Francis X. Vacanti, Joshua C. Vacanti, Assia Valovska, Ivan T. Valovski, Mary Ann Vann, Susan Vassallo, Anasuya Vasudevan, Kamen V. Vlassakov, Gian Paolo Volpato, Essi M. Vulli, J. Matthias Walz, Jingping Wang, James F. Watkins, Maxwell Weinmann, Sharon L. Wetherall, Mallory Williams, Sarah H. Wiser, Zhiling Xiong, Warren M. Zapol, Jie Zhou
- Edited by Charles Vacanti, Scott Segal, Pankaj Sikka, Richard Urman
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- Book:
- Essential Clinical Anesthesia
- Published online:
- 05 January 2012
- Print publication:
- 11 July 2011, pp xv-xxviii
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