The iMSMS: a multi-city, household controlled, gut microbiome study in multiple sclerosis
ECTRIMS Online Library. Zhou X. 09/12/19; 279503; 223
Xiaoyuan Zhou
Xiaoyuan Zhou
Contributions
Abstract

Abstract: 223

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - Microbiology and virology

X. Zhou1, S. Singh1, X. Jia1, P. Barba1, R. Baumann1, J. Landefeld1, P. Casaccia2,3, I. Katz Sand3, Z. Xia4, H. Weiner5, T. Chitnis5, S. Chandran6, P. Connick6, D. Otaegui7, T. Castillo-Triviño7, S. Caillier1, A. Santaniello1, L. Negrotto8, M. Farez8, R. Hohlfeld9, J.S. Graves10, A. Bar-Or11, J.R. Oksenberg1, T. West1, J. Correale1, B.A.C. Cree1, S.L. Hauser1, R. Knight12, S.E. Baranzini1, The iMSMS Consortium

1Department of Neurology, University of California, San Francisco, San Francisco, CA, 2Neuroscience Initiative, Advanced Science Research Center at GC-CUNY, 3Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 4Department of Neurology, University of Pittsburgh, Pittsburgh, PA, 5Department of Neurology, Brigham and Women's Hospital, Harvard School of Medicine, Boston, MA, United States, 6Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom, 7Neurosciences Area, Biodonostia Health Research Institute, San Sebastián, Spain, 8Department of Neurology, Institute for Neurological Research Dr. Raul Carrea (FLENI), Buenos Aires, Argentina, 9Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, München, Germany, 10Department of Neurosciences, University of California, San Diego, San Diego, CA, 11Department of Neurology, University of Pennsylvania, Pennsylvania, PA, 12Center for Microbiome Innovation, University of California, San Diego, San Diego, CA, United States

Background: The gut microbiota is emerging as a critical regulator of immune responses and appears to play an important pathogenic role in multiple autoimmune and neurological conditions. The International Multiple Sclerosis Microbiome study (iMSMS) is a global collaboration aimed at elucidating the role of commensal gut bacteria in MS by acquiring and analyzing samples from 2000 patients and 2000 household healthy controls.
Aims: Here we present an analysis of participants from 5 recruiting centers located in the US (West and East coasts), Europe and South America, focusing on identifying the main sources of variation in gut microbial abundance, and the stability across different sample collection strategies and of serial collection over a 3-day interval. These analyses will be critical to the development of statistical models to inform the full analysis.
Methods: 1005 snap frozen or desiccated Q-tip samples from 256 subjects (128 case:control pairs) were collected and evaluated by both, 16S and shallow whole metagenome shotgun sequencing (WMGS). The correlation between the two sequencing methodologies was tested. Also, univariate and multivariate linear regression analyses were conducted to understand patterns of variation on gut microbiome.
Results: The microbiome divergence by individual was significantly higher than the variance observed by collection method or across timepoints. In fact, the largest two sources of variance of gut microbiome emerged from the recruiting house and recruiting site while household MS:control pairs shared more similar microbiota than randomly paired individuals. Highly correlated microbial composition was observed between 16S rRNA and corresponding WMGS on both phylum and genus level.
Conclusion: Given the large effect of the collection site, the unique paired design of the iMSMS will likely serve to reduce this confounding variable and maximize the power of this and other similar studies. Shallow shotgun sequencing can be a cost-effective alternative of 16S on large-scale microbiome studies by expanding the microbiome structure analysis to functional investigation.
Disclosure: X. Zhou: Nothing to disclose
S. Singh: Nothing to disclose
X. Jia: Nothing to disclose
P. Barba: Nothing to disclose
R. Baumann: Nothing to disclose
James Landefeld: Nothing to disclose
P. Casaccia: No relevant discosures
I. Katz-Sand: No relevant discosures
Z. Xia: No relevant discosures
H. Weiner: Dr. Weiner reports grants from National Institutes of Health, grants from National Multiple Sclerosis Society, grants from Verily Life Sciences, grants from EMD Serono, grants from Biogen, grants from Teva Pharmaceuticals, grants from Sanofi, grants from Novartis, grants and personal fees from Genentech, Inc, grants and personal fees from Tilos Therapeutics, personal fees from Tiziana Life Sciences, personal fees from IM Therapeutics, personal fees from MedDay Pharmaceuticals, personal fees from vTv Therapeutics, outside the submitted work.
T. Chitnis: No relevant discosures
S. Chandran: No relevant discosures
P. Connick: No relevant discosures
D. Otaegui: No relevant discosures
T. Castillo-Triviño: No relevant discosures
Stacy Caillier: Nothing to disclose
Adam Santaniello: Nothing to disclose
L. Negrotto: No relevant discosures
M. Farez: No relevant discosures
R. Hohfeld: No relevant discosures
J. Graves: No relevant discosures
A. Bar-Or: No relevant discosures
Jorge R. Oksenberg: No relevant discosures
Timothy West: No relevant discosures
J. Correale: No relevant discosures
B.A.C. Cree: No relevant discosures
S.L. Hauser: No relevant discosures
R. Knight: No relevant discosures
S.E. Baranzini: No relevant discosures

Abstract: 223

Type: Scientific Session

Abstract Category: Pathology and pathogenesis of MS - Microbiology and virology

X. Zhou1, S. Singh1, X. Jia1, P. Barba1, R. Baumann1, J. Landefeld1, P. Casaccia2,3, I. Katz Sand3, Z. Xia4, H. Weiner5, T. Chitnis5, S. Chandran6, P. Connick6, D. Otaegui7, T. Castillo-Triviño7, S. Caillier1, A. Santaniello1, L. Negrotto8, M. Farez8, R. Hohlfeld9, J.S. Graves10, A. Bar-Or11, J.R. Oksenberg1, T. West1, J. Correale1, B.A.C. Cree1, S.L. Hauser1, R. Knight12, S.E. Baranzini1, The iMSMS Consortium

1Department of Neurology, University of California, San Francisco, San Francisco, CA, 2Neuroscience Initiative, Advanced Science Research Center at GC-CUNY, 3Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, 4Department of Neurology, University of Pittsburgh, Pittsburgh, PA, 5Department of Neurology, Brigham and Women's Hospital, Harvard School of Medicine, Boston, MA, United States, 6Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, United Kingdom, 7Neurosciences Area, Biodonostia Health Research Institute, San Sebastián, Spain, 8Department of Neurology, Institute for Neurological Research Dr. Raul Carrea (FLENI), Buenos Aires, Argentina, 9Institute of Clinical Neuroimmunology, Biomedical Center and University Hospitals, Ludwig-Maximilians-Universität München, München, Germany, 10Department of Neurosciences, University of California, San Diego, San Diego, CA, 11Department of Neurology, University of Pennsylvania, Pennsylvania, PA, 12Center for Microbiome Innovation, University of California, San Diego, San Diego, CA, United States

Background: The gut microbiota is emerging as a critical regulator of immune responses and appears to play an important pathogenic role in multiple autoimmune and neurological conditions. The International Multiple Sclerosis Microbiome study (iMSMS) is a global collaboration aimed at elucidating the role of commensal gut bacteria in MS by acquiring and analyzing samples from 2000 patients and 2000 household healthy controls.
Aims: Here we present an analysis of participants from 5 recruiting centers located in the US (West and East coasts), Europe and South America, focusing on identifying the main sources of variation in gut microbial abundance, and the stability across different sample collection strategies and of serial collection over a 3-day interval. These analyses will be critical to the development of statistical models to inform the full analysis.
Methods: 1005 snap frozen or desiccated Q-tip samples from 256 subjects (128 case:control pairs) were collected and evaluated by both, 16S and shallow whole metagenome shotgun sequencing (WMGS). The correlation between the two sequencing methodologies was tested. Also, univariate and multivariate linear regression analyses were conducted to understand patterns of variation on gut microbiome.
Results: The microbiome divergence by individual was significantly higher than the variance observed by collection method or across timepoints. In fact, the largest two sources of variance of gut microbiome emerged from the recruiting house and recruiting site while household MS:control pairs shared more similar microbiota than randomly paired individuals. Highly correlated microbial composition was observed between 16S rRNA and corresponding WMGS on both phylum and genus level.
Conclusion: Given the large effect of the collection site, the unique paired design of the iMSMS will likely serve to reduce this confounding variable and maximize the power of this and other similar studies. Shallow shotgun sequencing can be a cost-effective alternative of 16S on large-scale microbiome studies by expanding the microbiome structure analysis to functional investigation.
Disclosure: X. Zhou: Nothing to disclose
S. Singh: Nothing to disclose
X. Jia: Nothing to disclose
P. Barba: Nothing to disclose
R. Baumann: Nothing to disclose
James Landefeld: Nothing to disclose
P. Casaccia: No relevant discosures
I. Katz-Sand: No relevant discosures
Z. Xia: No relevant discosures
H. Weiner: Dr. Weiner reports grants from National Institutes of Health, grants from National Multiple Sclerosis Society, grants from Verily Life Sciences, grants from EMD Serono, grants from Biogen, grants from Teva Pharmaceuticals, grants from Sanofi, grants from Novartis, grants and personal fees from Genentech, Inc, grants and personal fees from Tilos Therapeutics, personal fees from Tiziana Life Sciences, personal fees from IM Therapeutics, personal fees from MedDay Pharmaceuticals, personal fees from vTv Therapeutics, outside the submitted work.
T. Chitnis: No relevant discosures
S. Chandran: No relevant discosures
P. Connick: No relevant discosures
D. Otaegui: No relevant discosures
T. Castillo-Triviño: No relevant discosures
Stacy Caillier: Nothing to disclose
Adam Santaniello: Nothing to disclose
L. Negrotto: No relevant discosures
M. Farez: No relevant discosures
R. Hohfeld: No relevant discosures
J. Graves: No relevant discosures
A. Bar-Or: No relevant discosures
Jorge R. Oksenberg: No relevant discosures
Timothy West: No relevant discosures
J. Correale: No relevant discosures
B.A.C. Cree: No relevant discosures
S.L. Hauser: No relevant discosures
R. Knight: No relevant discosures
S.E. Baranzini: No relevant discosures

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