Dietary fiber and the short-chain fatty acid acetate promote resolution of neutrophilic inflammation in a model of gout in mice

Abstract

Gout is a disease characterized by the deposition of monosodium urate (MSU) crystals in the joints. Continuous gout episodes may lead to unresolved inflammatory responses and tissue damage. We investigated the effects of a high‐fiber diet and acetate, a short‐chain fatty acid (SCFA) resulting from the metabolism of fiber by gut microbiota, on the inflammatory response in an experimental model of gout in mice. Injection of MSU crystals into the knee joint of mice induced neutrophil influx and inflammatory hypernociception. The onset of inflammatory response induced by MSU crystals was not altered in animals given a high‐fiber diet, but the high‐fiber diet induced faster resolution of the inflammatory response. Similar results were obtained in animals given the SCFA acetate. Acetate was effective, even when given after injection of MSU crystals at the peak of the inflammatory response and induced caspase‐dependent apoptosis of neutrophils that accounted for the resolution of inflammation. Resolution of neutrophilic inflammation was associated with decreased NF‐κB activity and enhanced production of anti‐inflammatory mediators, including IL‐10, TGF‐β, and annexin A1. Acetate treatment or intake of a high‐fiber diet enhanced efferocytosis, an effect also observed in vitro with neutrophils treated with acetate. In conclusion, a high‐fiber diet or one of its metabolic products, acetate, controls the inflammatory response to MSU crystals by favoring the resolution of the inflammatory response. Our studies suggest that what we eat plays a determinant role in our capacity to fine tune the inflammatory response. Introduction

Acetate coordinates neutrophil and ILC3 responses against C. difficile through FFAR2

“…Animals received oral pretreatment with acetate at 150 mM or placebo in the drinking water, as reported in other studies (Vieira et al, 2017). Acetate treatment started 1 d before addition of antibiotics and continued throughout the protocol.…”

Proteome changes in renal cortex and medulla induced by dietary supplementation with inulin‐type fructans in growing pigs

“…The inclusion of dried chicory root to the diet of pigs caused a significant upregulation of annexin A1 (ANXA1) in renal medulla. There is no information on the influence of inulin‐type fructans or its by‐products on the expression of this protein; however, Vieira et al () reported that acetate, one of the end products of inulin fermentation, upregulated ANXA1 expression in inflammatory cells harvested from mice. Moreover, we observed downregulated expression of medullary plastin‐2 (LCP1) in response to E2 diet.…”

Can glyphosate’s disruption of the gut microbiome and induction of sulfate deficiency explain the epidemic in gout and associated diseases in the industrialized world?

“…Inter alia, lysine acetylation prevents urate binding, and the acetate that is then brought into the cell as cargo can also serve as a buffering agent for the lysosomes. A recent study has shown that acetate supplementation does not reduce the magnitude of the initial inflammatory response in gout, but it accelerates the pace of resolution of the gout episode [171]. Dietary fibre works similarly, probably because it is metabolized to acetate and other short-chain fatty acids by anaerobic microbes in the colon.…”