Tzi Shin Toh1, Chun Wie Chong2, Shen-Yang Lim1, Jeff Bowman3, Mihai Cirstea4, Chin-Hsien Lin5, Chieh-Chang Chen6, Silke Appel-Cresswell7, B Brett Finlay8, Ai Huey Tan9. 1. Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 2. School of Pharmacy, Monash University Malaysia, Selangor, Malaysia. Electronic address: Chong.ChunWie@monash.edu. 3. Integrative Oceanography Division, Scripps Institution of Oceanography, University of California, California, USA; Center for Microbiome Innovation, UC San Diego, California, USA. 4. Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, UBC, Vancouver, British Columbia, Canada. 5. Department of Neurology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan. 6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. 7. Pacific Parkinson's Research Centre and Djavad Mowafaghian Centre for Brain Health, UBC, Vancouver, British Columbia, Canada; Division of Neurology, Faculty of Medicine, UBC, Vancouver, British Columbia, Canada. 8. Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada; Michael Smith Laboratories, UBC, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, UBC, Vancouver, British Columbia, Canada. 9. Division of Neurology, Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; Mah Pooi Soo & Tan Chin Nam Centre for Parkinson's & Related Disorders, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: aihuey.tan@gmail.com.
Abstract
BACKGROUND: Gut microbiome alterations have been reported in Parkinson's disease (PD), but with heterogenous findings, likely due to differences in study methodology and population. We investigated the main microbiome alterations in PD, their correlations with disease severity, and the impact of study and geographical differences. METHODS: After systematic screening, raw 16S rRNA gene sequences were obtained from ten case-control studies totaling 1703 subjects (969 PD, 734 non-PD controls; seven predominantly Caucasian and three predominantly non-Caucasian cohorts). Quality-filtered gene sequences were analyzed using a phylogenetic placement approach, which precludes the need for the sequences to be sourced from similar regions in the 16S rRNA gene, thus allowing a direct comparison between studies. Differences in microbiome composition and correlations with clinical variables were analyzed using multivariate statistics. RESULTS: Study and geography accounted for the largest variations in gut microbiome composition. Microbiome composition was more similar for subjects from the same study than those from different studies with the same disease status. Microbiome composition significantly differed between Caucasian and non-Caucasian populations. After accounting for study differences, microbiome composition was significantly different in PD vs. controls (albeit with a marginal effect size), with several distinctive features including increased abundances of Megasphaera and Akkermansia, and reduced Roseburia. Several bacterial genera correlated with PD motor severity, motor response complications and cognitive function. CONCLUSION: Consistent microbial features in PD merit further investigation. The large variations in microbiome findings of PD patients underscore the need for greater harmonization of future research, and personalized approaches in designing microbial-directed therapeutics.
BACKGROUND: Gut microbiome alterations have been reported in Parkinson's disease (PD), but with heterogenous findings, likely due to differences in study methodology and population. We investigated the main microbiome alterations in PD, their correlations with disease severity, and the impact of study and geographical differences. METHODS: After systematic screening, raw 16S rRNA gene sequences were obtained from ten case-control studies totaling 1703 subjects (969 PD, 734 non-PD controls; seven predominantly Caucasian and three predominantly non-Caucasian cohorts). Quality-filtered gene sequences were analyzed using a phylogenetic placement approach, which precludes the need for the sequences to be sourced from similar regions in the 16S rRNA gene, thus allowing a direct comparison between studies. Differences in microbiome composition and correlations with clinical variables were analyzed using multivariate statistics. RESULTS: Study and geography accounted for the largest variations in gut microbiome composition. Microbiome composition was more similar for subjects from the same study than those from different studies with the same disease status. Microbiome composition significantly differed between Caucasian and non-Caucasian populations. After accounting for study differences, microbiome composition was significantly different in PD vs. controls (albeit with a marginal effect size), with several distinctive features including increased abundances of Megasphaera and Akkermansia, and reduced Roseburia. Several bacterial genera correlated with PD motor severity, motor response complications and cognitive function. CONCLUSION: Consistent microbial features in PD merit further investigation. The large variations in microbiome findings of PD patients underscore the need for greater harmonization of future research, and personalized approaches in designing microbial-directed therapeutics.
Authors: Malena Dos Santos Guilherme; Francesco Valeri; Jennifer Winter; Marianne B Müller; Andreas Schwiertz; Kristina Endres Journal: Microorganisms Date: 2022-05-24