{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T00:43:23Z","timestamp":1792197803442,"version":"4.4.0"},"reference-count":66,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR34"],"award-info":[{"award-number":["TRR34"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TR156"],"award-info":[{"award-number":["TR156"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Bacterial sepsis is a major cause of mortality resulting from inadequate immune responses to systemic infection. Effective immunomodulatory approaches are urgently needed but it has remained elusive, which targets might be suitable for intervention. Increased expression of the G-protein-coupled receptor GPR43, which is known to govern intestinal responses to acetate, has been associated with sepsis patient survival but the mechanisms behind this observation have remained unclear. We show that elevated serum acetate concentrations prime neutrophils in a GPR43-dependent fashion, leading to enhanced neutrophil chemotaxis, oxidative burst, cytokine release and upregulation of phagocytic receptors. Consequently, acetate priming improved the capacity of human neutrophils to eliminate methicillin-resistant <jats:italic>Staphylococcus aureus<\/jats:italic>. Acetate administration increased mouse serum acetate concentrations and primed neutrophils. Notably, it rescued wild-type mice from severe <jats:italic>S. aureus<\/jats:italic> sepsis and reduced bacterial numbers in peripheral organs by several magnitudes. Acetate treatment improved the sepsis course even when applied several hours after onset of the infection, which recommends GPR43 as a potential target for sepsis therapy. Our study indicates that the severity of sepsis depends on transient neutrophil priming by appropriate blood acetate concentrations. Therapeutic interventions based on GPR43 stimulation could become valuable strategies for reducing sepsis-associated morbidity and mortality.<\/jats:p>","DOI":"10.1038\/s42003-021-02427-0","type":"journal-article","created":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T10:04:43Z","timestamp":1627639483000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Acetate sensing by GPR43 alarms neutrophils and protects from severe sepsis"],"prefix":"10.1038","volume":"4","author":[{"given":"Katja","family":"Schlatterer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Beck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Schoppmeier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-8626","authenticated-orcid":false,"given":"Andreas","family":"Peschel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorothee","family":"Kretschmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,7,30]]},"reference":[{"key":"2427_CR1","doi-asserted-by":"publisher","first-page":"e99","DOI":"10.1016\/S1473-3099(17)30485-1","volume":"18","author":"E Tacconelli","year":"2018","unstructured":"Tacconelli, E. et al. Surveillance for control of antimicrobial resistance. Lancet Infect. Dis. 18, e99\u2013e106 (2018).","journal-title":"Lancet Infect. Dis."},{"key":"2427_CR2","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","volume":"395","author":"KE Rudd","year":"2020","unstructured":"Rudd, K. E. et al. Global, regional, and national sepsis incidence and mortality, 1990\u20132017: analysis for the Global Burden of Disease Study. Lancet 395, 200\u2013211 (2020).","journal-title":"Lancet"},{"key":"2427_CR3","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1097\/00003246-200107000-00002","volume":"29","author":"DC Angus","year":"2001","unstructured":"Angus, D. C. et al. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit. Care Med. 29, 1303\u20131310 (2001).","journal-title":"Crit. Care Med."},{"key":"2427_CR4","doi-asserted-by":"publisher","first-page":"18033","DOI":"10.1038\/nrdp.2018.33","volume":"4","author":"AS Lee","year":"2018","unstructured":"Lee, A. S. et al. Methicillin-resistant Staphylococcus aureus. Nat. Rev. Dis. Prim. 4, 18033 (2018).","journal-title":"Nat. Rev. Dis. Prim."},{"key":"2427_CR5","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1128\/CMR.00134-14","volume":"28","author":"SY Tong","year":"2015","unstructured":"Tong, S. Y., Davis, J. S., Eichenberger, E., Holland, T. L. & Fowler, V. G. Jr. Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management. Clin. Microbiol. Rev. 28, 603\u2013661 (2015).","journal-title":"Clin. Microbiol. Rev."},{"key":"2427_CR6","doi-asserted-by":"publisher","first-page":"114850","DOI":"10.1016\/j.diagmicrobio.2019.06.002","volume":"95","author":"HS Sader","year":"2019","unstructured":"Sader, H. S., Castanheira, M., Streit, J. M. & Flamm, R. K. Frequency of occurrence and antimicrobial susceptibility of bacteria isolated from patients hospitalized with bloodstream infections in United States medical centers (2015-2017). Diagn. Microbiol. Infect. Dis. 95, 114850 (2019).","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"2427_CR7","doi-asserted-by":"publisher","first-page":"e422","DOI":"10.1016\/S1473-3099(19)30567-5","volume":"19","author":"I Rubio","year":"2019","unstructured":"Rubio, I. et al. Current gaps in sepsis immunology: new opportunities for translational research. Lancet Infect. Dis. 19, e422\u2013e436 (2019).","journal-title":"Lancet Infect. Dis."},{"key":"2427_CR8","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1177\/1751143718765407","volume":"19","author":"R Davies","year":"2018","unstructured":"Davies, R., O\u2019Dea, K. & Gordon, A. Immune therapy in sepsis: are we ready to try again? J. Intensive Care Soc. 19, 326\u2013344 (2018).","journal-title":"J. Intensive Care Soc."},{"key":"2427_CR9","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1159\/000487756","volume":"10","author":"SD Kobayashi","year":"2018","unstructured":"Kobayashi, S. D., Malachowa, N. & DeLeo, F. R. Neutrophils and bacterial immune evasion. J. Innate Immun. 10, 432\u2013441 (2018).","journal-title":"J. Innate Immun."},{"key":"2427_CR10","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/978-1-62703-845-4_1","volume":"1124","author":"HL Malech","year":"2014","unstructured":"Malech, H. L., Deleo, F. R. & Quinn, M. T. The role of neutrophils in the immune system: an overview. Methods Mol. Biol. 1124, 3\u201310 (2014).","journal-title":"Methods Mol. Biol."},{"key":"2427_CR11","doi-asserted-by":"publisher","first-page":"638","DOI":"10.1016\/j.intimp.2013.06.034","volume":"17","author":"K Futosi","year":"2013","unstructured":"Futosi, K., Fodor, S. & Mocsai, A. Neutrophil cell surface receptors and their intracellular signal transduction pathways. Int. Immunopharmacol. 17, 638\u2013650 (2013).","journal-title":"Int. Immunopharmacol."},{"key":"2427_CR12","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1016\/j.it.2018.08.005","volume":"39","author":"E Weiss","year":"2018","unstructured":"Weiss, E. & Kretschmer, D. Formyl-peptide receptors in infection, inflammation, and cancer. Trends Immunol. 39, 815\u2013829 (2018).","journal-title":"Trends Immunol."},{"key":"2427_CR13","first-page":"1","volume":"7","author":"NWM de Jong","year":"2019","unstructured":"de Jong, N. W. M., van Kessel, K. P. M. & van Strijp, J. A. G. Immune evasion by Staphylococcus aureus. Microbiol. Spectr. 7, 1\u201327 2019).","journal-title":"icrobiol. Spectr."},{"key":"2427_CR14","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.chom.2010.05.012","volume":"7","author":"D Kretschmer","year":"2010","unstructured":"Kretschmer, D. et al. Human formyl peptide receptor 2 senses highly pathogenic Staphylococcus aureus. Cell Host Microbe 7, 463\u2013473 (2010).","journal-title":"Cell Host Microbe"},{"key":"2427_CR15","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1111\/imr.12752","volume":"289","author":"T Lammermann","year":"2019","unstructured":"Lammermann, T. & Kastenmuller, W. Concepts of GPCR-controlled navigation in the immune system. Immunol. Rev. 289, 205\u2013231 (2019).","journal-title":"Immunol. Rev."},{"key":"2427_CR16","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1038\/nrmicro3390","volume":"13","author":"DA Bloes","year":"2015","unstructured":"Bloes, D. A., Kretschmer, D. & Peschel, A. Enemy attraction: bacterial agonists for leukocyte chemotaxis receptors. Nat. Rev. Microbiol. 13, 95\u2013104 (2015).","journal-title":"Nat. Rev. Microbiol."},{"key":"2427_CR17","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1111\/imr.12447","volume":"273","author":"J El-Benna","year":"2016","unstructured":"El-Benna, J. et al. Priming of the neutrophil respiratory burst: role in host defense and inflammation. Immunol. Rev. 273, 180\u2013193 (2016).","journal-title":"Immunol. Rev."},{"key":"2427_CR18","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1097\/MOH.0000000000000471","volume":"26","author":"KL Vogt","year":"2019","unstructured":"Vogt, K. L., Summers, C. & Condliffe, A. M. The clinical consequences of neutrophil priming. Curr. Opin. Hematol. 26, 22\u201327 (2019).","journal-title":"Curr. Opin. Hematol."},{"key":"2427_CR19","doi-asserted-by":"publisher","first-page":"1687","DOI":"10.1111\/jcmm.13112","volume":"21","author":"XF Shen","year":"2017","unstructured":"Shen, X. F., Cao, K., Jiang, J. P., Guan, W. X. & Du, J. F. Neutrophil dysregulation during sepsis: an overview and update. J. Cell. Mol. Med. 21, 1687\u20131697 (2017).","journal-title":"J. Cell. Mol. Med."},{"key":"2427_CR20","doi-asserted-by":"publisher","first-page":"25481","DOI":"10.1074\/jbc.M301403200","volume":"278","author":"E Le Poul","year":"2003","unstructured":"Le Poul, E. et al. Functional characterization of human receptors for short chain fatty acids and their role in polymorphonuclear cell activation. J. Biol. Chem. 278, 25481\u201325489 (2003).","journal-title":"J. Biol. Chem."},{"key":"2427_CR21","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1053\/j.gastro.2013.04.056","volume":"145","author":"MH Kim","year":"2013","unstructured":"Kim, M. H., Kang, S. G., Park, J. H., Yanagisawa, M. & Kim, C. H. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice. Gastroenterology 145, 396\u2013406 e391-e310 (2013).","journal-title":"Gastroenterology"},{"key":"2427_CR22","doi-asserted-by":"publisher","first-page":"28","DOI":"10.3389\/fimmu.2016.00028","volume":"7","author":"Z Ang","year":"2016","unstructured":"Ang, Z. & Ding, J. L. GPR41 and GPR43 in obesity and inflammation\u2014protective or causative? Front. Immunol. 7, 28 (2016).","journal-title":"Front. Immunol."},{"key":"2427_CR23","doi-asserted-by":"publisher","DOI":"10.1186\/s13104-018-3165-4","volume":"11","author":"ZJ Carr","year":"2018","unstructured":"Carr, Z. J. et al. Increased whole blood FFA2\/GPR43 receptor expression is associated with increased 30-day survival in patients with sepsis. BMC Res. Notes 11, 41 (2018).","journal-title":"BMC Res. Notes"},{"key":"2427_CR24","first-page":"73","volume":"6","author":"RH Richards","year":"1976","unstructured":"Richards, R. H., Dowling, J. A., Vreman, H. J., Feldman, C. & Weiner, M. W. Acetate levels in human plasma. Proc. Clin. Dial. Transpl. Forum 6, 73\u201379 (1976).","journal-title":"Proc. Clin. Dial. Transpl. Forum"},{"key":"2427_CR25","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1021\/acs.chemrev.6b00056","volume":"117","author":"G Milligan","year":"2017","unstructured":"Milligan, G., Shimpukade, B., Ulven, T. & Hudson, B. D. Complex pharmacology of free fatty acid receptors. Chem. Rev. 117, 67\u2013110 (2017).","journal-title":"Chem. Rev."},{"key":"2427_CR26","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1016\/0741-8329(85)90090-4","volume":"2","author":"H Nuutinen","year":"1985","unstructured":"Nuutinen, H., Lindros, K., Hekali, P. & Salaspuro, M. Elevated blood acetate as indicator of fast ethanol elimination in chronic alcoholics. Alcohol 2, 623\u2013626 (1985).","journal-title":"Alcohol"},{"key":"2427_CR27","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1093\/clinchem\/25.10.1787","volume":"25","author":"CD Tollinger","year":"1979","unstructured":"Tollinger, C. D., Vreman, H. J. & Weiner, M. W. Measurement of acetate in human blood by gas chromatography: effects of sample preparation, feeding, and various diseases. Clin. Chem. 25, 1787\u20131790 (1979).","journal-title":"Clin. Chem."},{"key":"2427_CR28","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1042\/CS20080642","volume":"117","author":"MA Vinolo","year":"2009","unstructured":"Vinolo, M. A. et al. Short-chain fatty acids stimulate the migration of neutrophils to inflammatory sites. Clin. Sci. 117, 331\u2013338 (2009).","journal-title":"Clin. Sci."},{"key":"2427_CR29","doi-asserted-by":"publisher","first-page":"533","DOI":"10.3389\/fphar.2018.00533","volume":"9","author":"M Li","year":"2018","unstructured":"Li, M., van Esch, B., Henricks, P. A. J., Folkerts, G. & Garssen, J. The anti-inflammatory effects of short chain fatty acids on lipopolysaccharide- or tumor necrosis factor alpha-stimulated endothelial cells via activation of GPR41\/43 and inhibition of HDACs. Front. Pharm. 9, 533 (2018).","journal-title":"Front. Pharm."},{"key":"2427_CR30","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1016\/j.bmcl.2009.11.112","volume":"20","author":"Y Wang","year":"2010","unstructured":"Wang, Y. et al. The first synthetic agonists of FFA2: discovery and SAR of phenylacetamides as allosteric modulators. Bioorg. Med. Chem. Lett. 20, 493\u2013498 (2010).","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"2427_CR31","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1136\/gut.28.10.1221","volume":"28","author":"JH Cummings","year":"1987","unstructured":"Cummings, J. H., Pomare, E. W., Branch, W. J., Naylor, C. P. & Macfarlane, G. T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 28, 1221\u20131227 (1987).","journal-title":"Gut"},{"key":"2427_CR32","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.tips.2013.02.002","volume":"34","author":"LB Bindels","year":"2013","unstructured":"Bindels, L. B., Dewulf, E. M. & Delzenne, N. M. GPR43\/FFA2: physiopathological relevance and therapeutic prospects. Trends Pharm. Sci. 34, 226\u2013232 (2013).","journal-title":"Trends Pharm. Sci."},{"key":"2427_CR33","doi-asserted-by":"publisher","first-page":"2033","DOI":"10.1172\/JCI27544","volume":"116","author":"PM Dang","year":"2006","unstructured":"Dang, P. M. et al. A specific p47phox -serine phosphorylated by convergent MAPKs mediates neutrophil NADPH oxidase priming at inflammatory sites. J. Clin. Investig. 116, 2033\u20132043 (2006).","journal-title":"J. Clin. Investig."},{"key":"2427_CR34","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/genomeA.01584-14","volume":"3","author":"M Sassi","year":"2015","unstructured":"Sassi, M., Sharma, D., Brinsmade, S. R., Felden, B. & Augagneur, Y. Genome sequence of the clinical isolate Staphylococcus aureus subsp. aureus strain UAMS-1. Genome Announc. 3, 1\u20132 (2015).","journal-title":"Genome Announc."},{"key":"2427_CR35","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1128\/MMBR.00005-09","volume":"73","author":"GA Somerville","year":"2009","unstructured":"Somerville, G. A. & Proctor, R. A. At the crossroads of bacterial metabolism and virulence factor synthesis in Staphylococci. Microbiol. Mol. Biol. Rev. 73, 233\u2013248 (2009).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2427_CR36","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.ceca.2005.01.019","volume":"37","author":"S Brechard","year":"2005","unstructured":"Brechard, S., Bueb, J. L. & Tschirhart, E. J. Interleukin-8 primes oxidative burst in neutrophil-like HL-60 through changes in cytosolic calcium. Cell Calcium 37, 531\u2013540 (2005).","journal-title":"Cell Calcium"},{"key":"2427_CR37","first-page":"668","volume":"221","author":"E Weiss","year":"2020","unstructured":"Weiss, E., Schlatterer, K., Beck, C., Peschel, A. & Kretschmer, D. Formyl-peptide receptor activation enhances phagocytosis of community-acquired methicillin-resistant Staphylococcus aureus. J. Infect. Dis. 221, 668\u2013678 (2020).","journal-title":"J. Infect. Dis."},{"key":"2427_CR38","doi-asserted-by":"publisher","first-page":"217","DOI":"10.3389\/fcimb.2017.00217","volume":"7","author":"I Miralda","year":"2017","unstructured":"Miralda, I., Uriarte, S. M. & McLeish, K. R. Multiple phenotypic changes define neutrophil priming. Front. Cell. Infect. Microbiol. 7, 217 (2017).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"2427_CR39","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1128\/MMBR.69.1.12-50.2005","volume":"69","author":"AJ Wolfe","year":"2005","unstructured":"Wolfe, A. J. The acetate switch. Microbiol. Mol. Biol. Rev. 69, 12\u201350 (2005).","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"2427_CR40","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1097\/QCO.0b013e3283528c9b","volume":"25","author":"MA Kovach","year":"2012","unstructured":"Kovach, M. A. & Standiford, T. J. The function of neutrophils in sepsis. Curr. Opin. Infect. Dis. 25, 321\u2013327 (2012).","journal-title":"Curr. Opin. Infect. Dis."},{"key":"2427_CR41","doi-asserted-by":"publisher","first-page":"4065362","DOI":"10.1155\/2018\/4065362","volume":"2018","author":"JM Patel","year":"2018","unstructured":"Patel, J. M. et al. Sepsis induces a dysregulated neutrophil phenotype that is associated with increased mortality. Mediators Inflamm. 2018, 4065362 (2018).","journal-title":"Mediators Inflamm."},{"key":"2427_CR42","doi-asserted-by":"publisher","first-page":"e12967","DOI":"10.1111\/eci.12967","volume":"48","author":"KL Vogt","year":"2018","unstructured":"Vogt, K. L., Summers, C., Chilvers, E. R. & Condliffe, A. M. Priming and de-priming of neutrophil responses in vitro and in vivo. Eur. J. Clin. Investig. 48, e12967 (2018).","journal-title":"Eur. J. Clin. Investig."},{"key":"2427_CR43","doi-asserted-by":"publisher","first-page":"1622","DOI":"10.1182\/bloodadvances.2018030585","volume":"3","author":"N Fine","year":"2019","unstructured":"Fine, N. et al. Primed PMNs in healthy mouse and human circulation are first responders during acute inflammation. Blood Adv. 3, 1622\u20131637 (2019).","journal-title":"Blood Adv."},{"key":"2427_CR44","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1093\/infdis\/jiw157","volume":"214","author":"S Uchiyama","year":"2016","unstructured":"Uchiyama, S. et al. Interferon alpha-enhanced clearance of group A Streptococcus despite neutropenia. J. Infect. Dis. 214, 321\u2013328 (2016).","journal-title":"J. Infect. Dis."},{"key":"2427_CR45","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1038\/nature08530","volume":"461","author":"KM Maslowski","year":"2009","unstructured":"Maslowski, K. M. et al. Regulation of inflammatory responses by gut microbiota and chemoattractant receptor GPR43. Nature 461, 1282\u20131286 (2009).","journal-title":"Nature"},{"key":"2427_CR46","doi-asserted-by":"publisher","first-page":"142","DOI":"10.3389\/fimmu.2018.00142","volume":"9","author":"I Galvao","year":"2018","unstructured":"Galvao, I. et al. The metabolic sensor GPR43 receptor plays a role in the control of Klebsiella pneumoniae infection in the lung. Front. Immunol. 9, 142 (2018).","journal-title":"Front. Immunol."},{"key":"2427_CR47","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11152-6","volume":"10","author":"KH Antunes","year":"2019","unstructured":"Antunes, K. H. et al. Microbiota-derived acetate protects against respiratory syncytial virus infection through a GPR43-type 1 interferon response. Nat. Commun. 10, 3273 (2019).","journal-title":"Nat. Commun."},{"key":"2427_CR48","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1007\/164_2016_50","volume":"236","author":"C Tang","year":"2017","unstructured":"Tang, C. & Offermanns, S. FFA2 and FFA3 in metabolic regulation. Handb. Exp. Pharm. 236, 205\u2013220 (2017).","journal-title":"Handb. Exp. Pharm."},{"key":"2427_CR49","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1124\/mol.115.102301","volume":"89","author":"D Bolognini","year":"2016","unstructured":"Bolognini, D., Tobin, A. B., Milligan, G. & Moss, C. E. The pharmacology and function of receptors for short-chain fatty acids. Mol. Pharm. 89, 388\u2013398 (2016).","journal-title":"Mol. Pharm."},{"key":"2427_CR50","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.3389\/fmicb.2019.01363","volume":"10","author":"S Jeong","year":"2019","unstructured":"Jeong, S., Kim, H. Y., Kim, A. R., Yun, C. H. & Han, S. H. Propionate ameliorates Staphylococcus aureus skin infection by attenuating bacterial growth. Front. Microbiol. 10, 1363 (2019).","journal-title":"Front. Microbiol."},{"key":"2427_CR51","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1056\/NEJMoa1204242","volume":"367","author":"A Perner","year":"2012","unstructured":"Perner, A. et al. Hydroxyethyl starch 130\/0.42 versus Ringer\u2019s acetate in severe sepsis. N. Engl. J. Med. 367, 124\u2013134 (2012).","journal-title":"N. Engl. J. Med."},{"key":"2427_CR52","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/1462-2920.13589","volume":"19","author":"P Louis","year":"2017","unstructured":"Louis, P. & Flint, H. J. Formation of propionate and butyrate by the human colonic microbiota. Environ. Microbiol. 19, 29\u201341 (2017).","journal-title":"Environ. Microbiol."},{"key":"2427_CR53","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1021\/acs.jproteome.5b01089","volume":"15","author":"DD Marshall","year":"2016","unstructured":"Marshall, D. D., Sadykov, M. R., Thomas, V. C., Bayles, K. W. & Powers, R. Redox imbalance underlies the fitness defect associated with inactivation of the Pta-AckA pathway in Staphylococcus aureus. J. Proteome Res. 15, 1205\u20131212 (2016).","journal-title":"J. Proteome Res."},{"key":"2427_CR54","doi-asserted-by":"publisher","first-page":"4724","DOI":"10.1128\/IAI.71.8.4724-4732.2003","volume":"71","author":"GA Somerville","year":"2003","unstructured":"Somerville, G. A. et al. Correlation of acetate catabolism and growth yield in Staphylococcus aureus: implications for host\u2013pathogen interactions. Infect. Immun. 71, 4724\u20134732 (2003).","journal-title":"Infect. Immun."},{"key":"2427_CR55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/microorganisms8050773","volume":"8","author":"RY Huang","year":"2020","unstructured":"Huang, R. Y., Raymond Herr, D. & Moochhala, S. manipulation of alcohol and short-chain fatty acids in the metabolome of commensal and virulent Klebsiella pneumoniae by linolenic acid. Microorganisms 8, 1\u20139 (2020).","journal-title":"Microorganisms"},{"key":"2427_CR56","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1002\/JLB.2A0318-130RR","volume":"104","author":"J Martensson","year":"2018","unstructured":"Martensson, J. et al. Neutrophil priming that turns natural FFA2R agonists into potent activators of the superoxide generating NADPH-oxidase. J. Leukoc. Biol. 104, 1117\u20131132 (2018).","journal-title":"J. Leukoc. Biol."},{"key":"2427_CR57","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1164\/rccm.201708-1559OC","volume":"197","author":"BH Singer","year":"2018","unstructured":"Singer, B. H. et al. Bacterial dissemination to the brain in sepsis. Am. J. Respir. Crit. Care Med. 197, 747\u2013756 (2018).","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2427_CR58","doi-asserted-by":"publisher","first-page":"e01361","DOI":"10.1128\/mBio.01361-14","volume":"5","author":"A Zaborin","year":"2014","unstructured":"Zaborin, A. et al. Membership and behavior of ultra-low-diversity pathogen communities present in the gut of humans during prolonged critical illness. mBio 5, e01361\u2013e01314 (2014).","journal-title":"mBio"},{"key":"2427_CR59","doi-asserted-by":"publisher","first-page":"e0167032","DOI":"10.1371\/journal.pone.0167032","volume":"11","author":"X Zhao","year":"2016","unstructured":"Zhao, X. et al. Sensitive and simplified detection of antibiotic influence on the dynamic and versatile changes of fecal short-chain fatty acids. PLoS ONE 11, e0167032 (2016).","journal-title":"PLoS ONE"},{"key":"2427_CR60","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa682","author":"WD Miller","year":"2020","unstructured":"Miller, W. D., Keskey, R. & Alverdy, J. C. Sepsis and the microbiome: a vicious cycle. J. Infect. Dis. https:\/\/doi.org\/10.1093\/infdis\/jiaa682 (2020).","journal-title":"J. Infect. Dis."},{"key":"2427_CR61","first-page":"1961","volume":"382","author":"Z DeFilipp","year":"2020","unstructured":"DeFilipp, Z., Bloom, P. P., Hohmann, E. L. & Group, F. M. T. S. Drug-resistant bacteremia after fecal microbiota transplant. Reply. N. Engl. J. Med. 382, 1961\u20131962 (2020).","journal-title":"N. Engl. J. Med."},{"key":"2427_CR62","doi-asserted-by":"publisher","unstructured":"Fava, F., Rizzetto, L. & Tuohy, K. M. Gut microbiota and health: connecting actors across the metabolic system. Proc. Nutr. Soc. 1\u201312, https:\/\/doi.org\/10.1017\/S0029665118002719 (2018).","DOI":"10.1017\/S0029665118002719"},{"key":"2427_CR63","doi-asserted-by":"publisher","first-page":"e39910","DOI":"10.1371\/journal.pone.0039910","volume":"7","author":"DA Bloes","year":"2012","unstructured":"Bloes, D. A., Otto, M., Peschel, A. & Kretschmer, D. Enterococcus faecium stimulates human neutrophils via the formyl-peptide receptor 2. PLoS ONE 7, e39910 (2012).","journal-title":"PLoS ONE"},{"key":"2427_CR64","doi-asserted-by":"publisher","first-page":"Tu3298","DOI":"10.1128\/genomeA.00112-16","volume":"4","author":"JC Moran","year":"2016","unstructured":"Moran, J. C. & Horsburgh, M. J. Whole-genome sequence of Staphylococcus epidermidis. Genome Announc. 4, Tu3298 (2016).","journal-title":"Genome Announc."},{"key":"2427_CR65","doi-asserted-by":"publisher","first-page":"214","DOI":"10.1086\/341454","volume":"186","author":"LV Collins","year":"2002","unstructured":"Collins, L. V. et al. Staphylococcus aureus strains lacking d-alanine modifications of teichoic acids are highly susceptible to human neutrophil killing and are virulence attenuated in mice. J. Infect. Dis. 186, 214\u2013219 (2002).","journal-title":"J. Infect. Dis."},{"key":"2427_CR66","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/nm.3779","volume":"21","author":"C Tang","year":"2015","unstructured":"Tang, C. et al. Loss of FFA2 and FFA3 increases insulin secretion and improves glucose tolerance in type 2 diabetes. Nat. Med. 21, 173\u2013177 (2015).","journal-title":"Nat. Med."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02427-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02427-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02427-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,5]],"date-time":"2023-02-05T08:13:04Z","timestamp":1675584784000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-021-02427-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,30]]},"references-count":66,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["2427"],"URL":"https:\/\/doi.org\/10.1038\/s42003-021-02427-0","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,30]]},"assertion":[{"value":"13 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 June 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 July 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"928"}}