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Biomolecules 2019, 9(4), 144;

Host-Microbiome Synergistic Control on Sphingolipid Metabolism by Mechanotransduction in Model Arthritis

Department of Neurology, University of California, San Francisco, CA 94158, USA
CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, China
Bioinformatics Platform, Institut Pasteur of Shanghai, CAS, Shanghai 200031, China
NORSAS Consultancy Ltd., Hoveton, Norwich, Norfolk, NR128QP, UK
Department of Laboratory Medicine, Division of Clinical Chemistry Karolinska Institute, 17177 Stockholm, Sweden
Scientific and Medical Direction, SOL Group S.r.l, 20900 Monza, Italy
CNR IAC "Mauro Picone", 00185 Roma, Italy
Authors to whom correspondence should be addressed.
Received: 6 February 2019 / Revised: 1 April 2019 / Accepted: 3 April 2019 / Published: 9 April 2019
(This article belongs to the Special Issue Mechanobiology in Health and Disease)
PDF [1953 KB, uploaded 9 April 2019]


Chronic inflammatory autoimmune disorders are systemic diseases with increasing incidence and still lack a cure. More recently, attention has been placed in understanding gastrointestinal (GI) dysbiosis and, although important progress has been made in this area, it is currently unclear to what extent microbiome manipulation can be used in the treatment of autoimmune disorders. Via the use of appropriate models, rheumatoid arthritis (RA), a well-known exemplar of such pathologies, can be exploited to shed light on the currently overlooked effects of existing therapies on the GI microbiome. In this direction, we here explore the crosstalk between the GI microbiome and the host immunity in model arthritis (collagen induced arthritis, CIA). By exploiting omics from samples of limited invasiveness (blood and stools), we assess the host-microbiome responses to standard therapy (methotrexate, MTX) combined with mechanical subcutaneous stimulation (MS) and to mechanical stimulation alone. When MS is involved, results reveal the sphingolipid metabolism as the trait d’union among known hallmarks of (model) RA, namely: Imbalance in the S1P-S1PR1 axis, expansion of Prevotella sp., and invariant Natural Killer T (iNKT)-penia, thus offering the base of a rationale to mechanically modulate this pathway as a therapeutic target in RA.
Keywords: rheumatoid arthritis; host-microbiome interaction; sphingolipids metabolism; Prevotella sp.; iNKT rheumatoid arthritis; host-microbiome interaction; sphingolipids metabolism; Prevotella sp.; iNKT
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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    Description: Data S1: Categorial and continuous phenotypic data for the progression of CIA; Data S2: Differential fecal 16SrRNA data analysis; Data S3: KEGG pathways significantly enriched by differential microbiome KEGG orthologies; Data S4: Differential PBMC mRNA analysis and functional enrichment; Data S5: Significantly enriched KEGG pathways by both PICRUST predicted metagenome KOs and blood gene; Data S6: Microbial differential analysis in previous data [16].

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Zhou, X.; Devescovi, V.; Liu, Y.; Dent, J.E.; Nardini, C. Host-Microbiome Synergistic Control on Sphingolipid Metabolism by Mechanotransduction in Model Arthritis. Biomolecules 2019, 9, 144.

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