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Alterations of the Gut Mycobiome in Patients with MS
25 Pages Posted: 23 Feb 2021More...
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: Suggested Citation