ORCID Profile
0000-0002-4556-7671
Current Organisation
Universidade Federal de Minas Gerais
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Publisher: Wiley
Date: 25-05-2015
DOI: 10.1002/ART.39107
Abstract: Host–microbial interactions are central in health and disease. Monosodium urate monohydrate (MSU) crystals cause gout by activating the NLRP3 inflammasome, leading to interleukin‐1β (IL‐1β) production and neutrophil recruitment. This study was undertaken to investigate the relevance of gut microbiota, acetate, and the metabolite‐sensing receptor GPR43 in regulating inflammation in a murine model of gout. Gout was induced by the injection of MSU crystals into the knee joints of mice. Macrophages from the various animals were stimulated to determine inflammasome activation and production of reactive oxygen species (ROS). Injection of MSU crystals caused joint inflammation, as seen by neutrophil influx, hypernociception, and production of IL‐1β and CXCL1. These parameters were greatly decreased in germ‐free mice, mice treated with antibiotics, and GPR‐43–deficient mice. Recolonization or administration of acetate to germ‐free mice restored inflammation in response to injection of MSU crystals. In vitro, macrophages produced ROS and assembled the inflammasome when stimulated with MSU. Macrophages from germ‐free animals produced little ROS, and there was little inflammasome assembly. Similar results were observed in macrophages from GPR‐43–deficient mice. Treatment of germ‐free mice with acetate restored in vitro responsiveness of macrophages to MSU crystals. In the absence of microbiota, there is decreased production of short‐chain fatty acids that are necessary for adequate inflammasome assembly and IL‐1β production in a manner that is at least partially dependent on GPR43. These results clearly show that the commensal microbiota shapes the host's ability to respond to an inflammasome‐dependent acute inflammatory stimulus outside the gut.
Publisher: Springer Science and Business Media LLC
Date: 22-07-2019
DOI: 10.1038/S41467-019-11152-6
Abstract: Severe respiratory syncytial virus (RSV) infection is a major cause of morbidity and mortality in infants years-old. Here we describe that high-fiber diet protects mice from RSV infection. This effect was dependent on intestinal microbiota and production of acetate. Oral administration of acetate mediated interferon-β (IFN-β) response by increasing expression of interferon-stimulated genes in the lung. These effects were associated with reduction of viral load and pulmonary inflammation in RSV-infected mice. Type 1 IFN signaling via the IFN-1 receptor (IFNAR) was essential for acetate antiviral activity in pulmonary epithelial cell lines and for the acetate protective effect in RSV-infected mice. Activation of Gpr43 in pulmonary epithelial cells reduced virus-induced cytotoxicity and promoted antiviral effects through IFN-β response. The effect of acetate on RSV infection was abolished in Gpr43 − / − mice. Our findings reveal antiviral effects of acetate involving IFN-β in lung epithelial cells and engagement of GPR43 and IFNAR.
Publisher: Wiley
Date: 15-12-2012
Publisher: Frontiers Media SA
Date: 20-02-2018
Publisher: Oxford University Press (OUP)
Date: 05-08-2016
DOI: 10.1189/JLB.3A1015-453RRR
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
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 10-2009
DOI: 10.1038/NATURE08530
Publisher: Springer Science and Business Media LLC
Date: 04-2015
DOI: 10.1038/NCOMMS7734
Abstract: Diet and the gut microbiota may underpin numerous human diseases. A major metabolic product of commensal bacteria are short-chain fatty acids (SCFAs) that derive from fermentation of dietary fibre. Here we show that diets deficient or low in fibre exacerbate colitis development, while very high intake of dietary fibre or the SCFA acetate protects against colitis. SCFAs binding to the 'metabolite-sensing' receptors GPR43 and GPR109A in non-haematopoietic cells mediate these protective effects. The inflammasome pathway has hitherto been reported as a principal pathway promoting gut epithelial integrity. SCFAs binding to GPR43 on colonic epithelial cells stimulates K(+) efflux and hyperpolarization, which lead to NLRP3 inflammasome activation. Dietary fibre also shapes gut bacterial ecology, resulting in bacterial species that are more effective for inflammasome activation. SCFAs and metabolite receptors thus explain health benefits of dietary fibre, and how metabolite signals feed through to a major pathway for gut homeostasis.
No related grants have been discovered for Angelica Vieira.