Alterations of the gut mycobiome in patients with MS
Saumya Shah,
Alberto Locca,
Yair Dorsett,
Claudia Cantoni,
Laura Ghezzi,
Qingqi Lin,
Suresh Bokoliya,
Hunter Panier,
Cassandra Suther,
Matthew Gormley,
Yue Liu,
Emily Evans,
Robert Mikesell,
Kathleen Obert,
Amber Salter,
Anne H Cross,
Phillip I. Tarr,
Amy Lovett-Racke,
Laura Piccio,
Yanjiao Zhou
Affiliations
Saumya Shah
Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, USA
Alberto Locca
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Yair Dorsett
Department of Medicine, UConn Health, Farmington, CT, USA
Claudia Cantoni
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Laura Ghezzi
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; University of Milan, Dino Ferrari Centre, Milan, Italy
Qingqi Lin
Department of Computer Science and Engineering, University of Connecticut, Storrs, CT, USA
Suresh Bokoliya
Department of Medicine, UConn Health, Farmington, CT, USA
Hunter Panier
Department of Medicine, UConn Health, Farmington, CT, USA
Cassandra Suther
Department of Medicine, UConn Health, Farmington, CT, USA; Department of Food Science, University of Massachusetts, Amherst, MA, USA
Matthew Gormley
Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH, USA
Yue Liu
Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH, USA
Emily Evans
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Robert Mikesell
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Kathleen Obert
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA
Amber Salter
Division of Biostatistics, School of Medicine, Washington University, St. Louis, MO, USA
Anne H Cross
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA
Phillip I. Tarr
Department of Pediatrics and Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, USA
Amy Lovett-Racke
Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH, USA
Laura Piccio
Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA; Brain and Mind Centre, School of Medical Sciences, University of Sydney, Sydney, NSW 2050, Australia; Corresponding author: Department of Neurology, Washington University School of Medicine, St. Louis, MO, USA.
Yanjiao Zhou
Department of Medicine, UConn Health, Farmington, CT, USA; Corresponding author. Department of Medicine, UConn Health, Farmington, CT, USA
Background: 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. Methods: In this case-control observational study, we performed ITS sequencing and characterised the gut mycobiome in people with MS (pwMS) and healthy controls at baseline and after six months. Findings: 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 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. Interpretation: There is an alteration of the gut mycobiome in pwMS, compared to healthy controls. Further study is required to assess any causal association of the mycobiome with MS and its direct or indirect interactions with bacteria and autoimmunity. Funding: 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) and by donations from Whitelaw Terry, Jr. / Valerie Terry Fund. 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 of the Barnes-Jewish Hospital Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
