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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02736

Exacerbation of chikungunya virus rheumatic immunopathology by a high fiber diet and butyrate

 Andreas Suhrbier1, 2*, Natalie A. Prow1, 2,  Thiago D. Hirata3, Bing Tang1, Thibaut Larcher4,  Pamela Mukhopadhyay1,  Tiago Lubiana Alves3,  Thuy T. Le1, Joy Gardner1,  Yee Suan Poo1,  Eri Nakayama5, Viviana P. Lutzky1 and  Helder Nakaya3
  • 1QIMR Berghofer Medical Research Institute, Australia
  • 2Australian Infectious Disease Research Centre, University of Queensland, Australia
  • 3Computational Systems Biology Laboratory, Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil
  • 4Institut National de la Recherche Agronomique, Université Paris-Saclay, France
  • 5Department of Virology II, National Institute of Infectious Diseases (NIID), Japan

Chikungunya virus (CHIKV) is a mosquito transmitted alphavirus associated with a robust systemic infection and an acute inflammatory rheumatic disease. A high fiber diet has been widely promoted for its ability to ameliorate inflammatory diseases. Fiber is fermented in the gut into short chain fatty acids such as acetate, propionate and butyrate, which enter the circulation providing systemic anti-inflammatory activities. Herein we show that mice fed a high fiber diet show a clear worsening of CHIKV arthropathy, with increased edema and neutrophil infiltrates. RNA-Seq analyses illustrated that a high fiber diet, in this setting, promoted a range of pro-neutrophil responses including Th17/IL-17. Gene Set Enrichment Analyses further demonstrated significant similarities with mouse models of inflammatory psoriasis and significant depression of macrophage resolution phase signatures in the CHIKV arthritic lesions from mice fed a high fiber diet. Supplementation of the drinking water with butyrate also increased edema after CHIKV infection. However, the mechanisms involved were different, with modulation of AP-1 and NF-κB responses identified, potentially implicating deoptimization of endothelial barrier repair. Thus neither fiber nor SCFAs provided benefits in this acute infectious disease setting, which is characterized by widespread viral cytopathic effects and a need for tissue repair.

Keywords: Chikungunya, immunopathology, Arthritis, Fiber, Diet

Received: 26 Jul 2019; Accepted: 08 Nov 2019.

Copyright: © 2019 Suhrbier, Prow, Hirata, Tang, Larcher, Mukhopadhyay, Alves, Le, Gardner, Poo, Nakayama, Lutzky and Nakaya. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Andreas Suhrbier, QIMR Berghofer Medical Research Institute, Brisbane, Australia,