The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
A Role for Gut Microbiota and the Metabolite‐Sensing Receptor GPR43 in a Murine Model of Gout
Abstract
Objective: 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. Methods: 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). Results: 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. Conclusion: 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.
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Cites
Gout-associated uric acid crystals activate the NALP3 inflammasome
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Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation
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Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43
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Self-citationInnate Immune Activation Through Nalp3 Inflammasome Sensing of Asbestos and Silica
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Dysregulation of Allergic Airway Inflammation in the Absence of Microbial Colonization
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The essential role of the intestinal microbiota in facilitating acute inflammatory responses
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Cited by
Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism
Morrison, D. J., & Preston, T. (2016) · Gut Microbes · doi:10.1080/19490976.2015.1134082 · Cited by 3,781
Gut microbiota, metabolites and host immunity
Rooks, M. G., & Garrett, W. S. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.42 · Cited by 3,409
Free Fatty Acid Receptors in Health and Disease
Kimura, I., Ichimura, A., Ohue-Kitano, R., & Igarashi, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00041.2018 · Cited by 1,018
Impact of Omega-3 Fatty Acids on the Gut Microbiota
Costantini, L., Molinari, R., Farinon, B., & Merendino, N. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18122645 · Cited by 741
Inflammation in gout: mechanisms and therapeutic targets
So, A. K., & Martinon, F. (2017) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2017.155 · Cited by 608
Metadata
- Authors
- Vieira, A. T., Macia, L., Galvão, I., Martins, F. S., Canesso, M. C. C., Amaral, F. A., Garcia, C. C., Maslowski, K. M., De Leon, E., Shim, D., Nicoli, J. R., Harper, J. L., Teixeira, M. M., & Mackay, C. R.
- Venue
- Arthritis & Rheumatology
- Publisher
- Wiley
- Published
- 2015-05-25
- Volume
- 67
- Issue
- 6
- Pages
- 1646-1656
- ISSN
- 2326-5191 (ISSN-L)
- 2326-5205
- OpenAlex
- W1618714494
- Cited by
- 254
- References
- 11
- FWCI
- 17.71
- Type
- journal article
- Language
- en
- Open access
- closed
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- Vieira, A. T., Macia, L., Galvão, I., Martins, F. S., Canesso, M. C. C., Amaral, F. A., Garcia, C. C., Maslowski, K. M., De Leon, E., Shim, D., Nicoli, J. R., Harper, J. L., Teixeira, M. M., & Mackay, C. R. (2015). A Role for Gut Microbiota and the Metabolite‐Sensing Receptor GPR43 in a Murine Model of Gout. Arthritis & Rheumatology. https://doi.org/10.1002/art.39107
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