title: 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.
authors: Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil.|Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Minas Gerais, Brazil.
authors: Angélica T
authors: AT
authors: Vieira
authors: Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil.
authors: Izabela
authors: I
authors: Galvão
authors: Department of Immunology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia; and.
authors: Laurence M
authors: LM
authors: Macia
authors: Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, São Paulo, Brazil.
authors: Érica M
authors: ÉM
authors: Sernaglia
authors: Department of Genetics, Evolution and Bioagents, Institute of Biology, University of Campinas, São Paulo, Brazil.
authors: Marco Aurélio R
authors: MA
authors: Vinolo
authors: Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil.
authors: Cristiana C
authors: CC
authors: Garcia
authors: Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil.
authors: Luciana P
authors: LP
authors: Tavares
authors: Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil.
authors: Flávio A
authors: FA
authors: Amaral
authors: Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil.
authors: Lirlândia P
authors: LP
authors: Sousa
authors: Department of Microbiology, Institute of Biological Sciences, Federal University of Minas Gerais (UFMG), Minas Gerais, Brazil.
authors: Flaviano S
authors: FS
authors: Martins
authors: Department of Immunology, Faculty of Medicine, Nursing and Health Sciences, Monash University, Clayton, Victoria, Australia; and.
authors: Charles R
authors: CR
authors: Mackay
authors: Immunopharmacology Group, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, Brazil; mmtex@icb.ufmg.br.
authors: Mauro M
authors: MM
authors: Teixeira
mesh_terms: D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D003460:Crystallization; D059305:Diet, High-Fat; D004043:Dietary Fiber / Q000494:pharmacology*; D004195:Disease Models, Animal; D006073:Gout / Q000473:pathology*; D007249:Inflammation / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism; D007596:Joints / Q000187:drug effects / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000473:pathology*; D010587:Phagocytosis / Q000187:drug effects; D014527:Uric Acid
chemical_list: D000085:Acetates; D004043:Dietary Fiber; D018836:Inflammation Mediators; D016328:NF-kappa B; D014527:Uric Acid; D020169:Caspases
keywords: arthritis; immunoregulation; microbiota