Exacerbation of Chikungunya Virus Rheumatic Immunopathology by a High Fiber Diet and Butyrate

Abstract

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 exacerbation 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 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 short chain fatty acids provided benefits in this acute infectious disease setting, which is characterized by widespread viral cytopathic effects and a need for tissue repair.

Nutritional status impacts dengue virus infection in mice

“…Finally, the microbiome plays a critical role in responding to pathogens. A recent report showed that a high-fiber diet increased levels of microbiome-induced short-chain fatty acid (SCFAs), resulting in more severe CHIKV disease [88]. Currently, there is a lack of studies identifying the influence of the microbiome on DENV infection, which is a critical gap in the literature.…”

Systems vaccinology analysis of a recombinant vaccinia-based vector reveals diverse innate immune signatures at the injection site

“…Immunohistochemistry (IHC) with a neutrophil-specific marker, anti-Ly6G (Poo et al ., 2014; Prow et al ., 2019), illustrated that the infiltrates contained abundant neutrophils (Fig. 1E, top panel, Ly6G).…”

Tenth Scientific Biennial Meeting of the Australasian Virology Society—AVS10 2019

“…Andreas Suhrbier (QIMR Berhofer Medical Research Institute, Brisbane, Australia) presented his novel findings surrounding the counter intuitive role of a high-fibre diet in the exacerbation of Chikungunya viral infection [4]. High-fibre diets and their gut fermented by-products are known to reduce inflammation in non-infectious settings; however, Andreas's team has now demonstrated that high-fibre diets, which results in the production by gut microbiota of the short-chain fatty acid butyrate, significantly enhanced viral driven cytopathic effects.…”

“…AVS10 travel awards. University of Western Australia, Perth, Australia;4 School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, Australia.…”