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Alterations of the Gut Mycobiome in Patients with MS

25 Pages Posted: 23 Feb 2021

See all articles by Saumya Shah

Saumya Shah

Department of Computer Science and Engineering, University of Connecticut

Alberto Locca

Department of Neurology, Washington University School of Medicine

Yair Dorsett

Department of Medicine, UConn Health

Claudia Cantoni

Department of Neurology, Washington University School of Medicine

Laura Ghezzi

Department of Neurology, Washington University School of Medicine

Qingqi Lin

Department of Computer Science and Engineering, University of Connecticut

Suresh Bokoliya

Department of Medicine, UConn Health

Hunter Panier

Department of Medicine, UConn Health

Cassandra Suther

Department of Medicine, UConn Health

Matthew Gormley

Department of Microbial Infection and Immunity, Ohio State University

Yue Liu

Department of Microbial Infection and Immunity, Ohio State University

Robert Mikesell

Department of Neurology, Washington University School of Medicine

Kathleen Obert

Department of Neurology, Washington University School of Medicine

Amber Salter

COViMS

Anne H. Cross

Department of Neurology, Washington University School of Medicine

Emily Evans

Department of Neurology, Washington University School of Medicine

Phillip I. Tarr

Departments of Pediatrics and Molecular Microbiology, Washington University School of Medicine

Amy Lovett-Racke

Department of Microbial Infection and Immunity, Ohio State University

Laura Piccio

Washington University in St. Louis - Department of Neurology

Yanjiao Zhou

University of Connecticut - School of Medicine

More...

Abstract

The mycobiome is the fungal component of the gut microbiome and is implicated in several autoimmune diseases. However, its role in MS has not been studied. We performed ITS sequencing and characterized the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months. The mycobiome had significantly higher alpha diversity and inter-subject variation in pwMS than controls. Saccharomyces and Aspergillus were over-represented in pwMS. Saccharomyces was positively correlated with circulating basophils and negatively correlated with regulatory B cells, while Aspergillus was positively correlated with activated CD16+ dendritic cells in pwMS. Different mycobiome profiles, defined as mycotypes, were associated with different bacterial microbiome and immune cell subsets in the peripheral blood. Initial treatment with dimethyl fumarate, a common immunomodulatory therapy which also has fungicidal activity, did not cause uniform gut mycobiome changes across all pwMS. Further study is required to assess any causal association of the mycobiome in MS and its direct or indirect interactions with bacteria and autoimmunity.

Funding Statement: This work was supported by the Washington University in St. Louis Institute of Clinical and Translational Sciences, funded, in part, by Grant Number # UL1 TR000448] from the National Institutes of Health, National Center for Advancing Translational Sciences, Clinical and Translational Sciences Award (Zhou Y, Piccio, L, Lovett-Racke A and Tarr PI). R01 NS102633-04 (Zhou Y, Piccio L). The Leon and Harriet Felman Fund for Human MS Research (Piccio L and Cross AH). Cantoni C. was supported by the National MS Society Career Transition Fellowship (TA-1805-31003). Ghezzi L. was supported by the Italian Multiple Sclerosis Society research fellowship (FISM 2018/B/1) and the National Multiple Sclerosis Society Post-Doctoral Fellowship (FG-1907-34474). Anne Cross was supported by The Manny & Rosalyn Rosenthal-Dr. John L. Trotter MS Center Chair in Neuroimmunology and the Barnes-Jewish Hospital Foundation.

Declaration of Interests: Dr. Evans has been a paid consultant and/or speaker for the following: Biogen, EMD Serono, National MS Society, Genentech/Roche, Novartis, Sanofi/Genzyme & Teva. Dr. Cross has done paid consulting for: Biogen, Celgene, EMD Serono, Genentech/Roche, Greenwich Biosciences, Janssen and Novartis, and has contracted research funded by EMD Serono and Genentech. Dr. Tarr is a consultant to, a member of the Scientific Advisory Board of, and a holder equity in, MediBeacon Inc, which is developing a method to test intestinal permeability in humans. He might receive royalty payments if the product generates revenues. All other authors have nothing to declare.

Ethics Approval Statement: The study was approved by the Human Research Protection
Office at Washington University in St. Louis School of Medicine (WUSM) (approval number: 201502105).

Suggested Citation

Shah, Saumya and Locca, Alberto and Dorsett, Yair and Cantoni, Claudia and Ghezzi, Laura and Lin, Qingqi and Bokoliya, Suresh and Panier, Hunter and Suther, Cassandra and Gormley, Matthew and Liu, Yue and Mikesell, Robert and Obert, Kathleen and Salter, Amber and Cross, Anne H. and Evans, Emily and Tarr, Phillip I. and Lovett-Racke, Amy and Piccio, Laura and Zhou, Yanjiao, Alterations of the Gut Mycobiome in Patients with MS. Available at SSRN: https://ssrn.com/abstract=3783095 or http://dx.doi.org/10.2139/ssrn.3783095

Saumya Shah

Department of Computer Science and Engineering, University of Connecticut ( email )

Alberto Locca

Department of Neurology, Washington University School of Medicine ( email )

Yair Dorsett

Department of Medicine, UConn Health ( email )

Claudia Cantoni

Department of Neurology, Washington University School of Medicine ( email )

Laura Ghezzi

Department of Neurology, Washington University School of Medicine ( email )

Qingqi Lin

Department of Computer Science and Engineering, University of Connecticut ( email )

Suresh Bokoliya

Department of Medicine, UConn Health ( email )

Hunter Panier

Department of Medicine, UConn Health ( email )

Cassandra Suther

Department of Medicine, UConn Health ( email )

Matthew Gormley

Department of Microbial Infection and Immunity, Ohio State University ( email )

Yue Liu

Department of Microbial Infection and Immunity, Ohio State University

Robert Mikesell

Department of Neurology, Washington University School of Medicine ( email )

Kathleen Obert

Department of Neurology, Washington University School of Medicine ( email )

Amber Salter

COViMS ( email )

Anne H. Cross

Department of Neurology, Washington University School of Medicine ( email )

Emily Evans

Department of Neurology, Washington University School of Medicine

Phillip I. Tarr

Departments of Pediatrics and Molecular Microbiology, Washington University School of Medicine ( email )

Amy Lovett-Racke

Department of Microbial Infection and Immunity, Ohio State University ( email )

Laura Piccio

Washington University in St. Louis - Department of Neurology ( email )

St. Louis, MO
United States

Yanjiao Zhou (Contact Author)

University of Connecticut - School of Medicine ( email )

263 Farmington Ave.
Farmington, CT 06030-2103
United States

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