Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease
Host-microbial cross-talk plays a crucial role in maintenance of gut homeostasis. However, how microbiota-derived metabolites, e.g., butyrate, regulate functions of neutrophils in the pathogenesis of inflammatory bowel disease (IBD) remains elusive. We sought to investigate the effects of butyrate o...
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doaj-4445b376a42b42e8829f88cb481cac3d2021-09-20T13:17:21ZengTaylor & Francis GroupGut Microbes1949-09761949-09842021-01-0113110.1080/19490976.2021.19682571968257Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel diseaseGengfeng Li0Jian Lin1Cui Zhang2Han Gao3Huiying Lu4Xiang Gao5Ruixin Zhu6Zhitao Li7Mingsong Li8Zhanju Liu9Shanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai Tenth People’s Hospital, Tongji University School of MedicineShanghai Tenth People’s Hospital, Tongji University School of MedicineSchool of Basic Medical Sciences, Henan University of Science and TechnologyThird Affiliated Hospital of Guangzhou Medical UniversityShanghai Tenth People’s Hospital, Tongji University School of MedicineHost-microbial cross-talk plays a crucial role in maintenance of gut homeostasis. However, how microbiota-derived metabolites, e.g., butyrate, regulate functions of neutrophils in the pathogenesis of inflammatory bowel disease (IBD) remains elusive. We sought to investigate the effects of butyrate on IBD neutrophils and elucidate the therapeutic potential in regulating mucosal inflammation. Peripheral neutrophils were isolated from IBD patients and healthy donors, and profiles of proinflammatory cytokines and chemokines were determined by qRT-PCR and ELISA, respectively. The migration and release of neutrophil extracellular traps (NETs) were studied by a Transwell model and immunofluorescence, respectively. The in vivo role of butyrate in regulating IBD neutrophils was evaluated in a DSS-induced colitis model in mice. We found that butyrate significantly inhibited IBD neutrophils to produce proinflammatory cytokines, chemokines, and calprotectins. Blockade of GPCR signaling with pertussis toxin (PTX) did not interfere the effects whereas pan-histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) effectively mimicked the role of butyrate. Furthermore, in vitro studies confirmed that butyrate suppressed neutrophil migration and formation of NETs from both CD and UC patients. RNA sequencing analysis revealed that the immunomodulatory effects of butyrate on IBD neutrophils were involved in leukocyte activation, regulation of innate immune response and response to oxidative stress. Consistently, oral administration of butyrate markedly ameliorated mucosal inflammation in DSS-induced murine colitis through inhibition of neutrophil-associated immune responses such as proinflammatory mediators and NET formation. Our data thus reveal that butyrate constrains neutrophil functions and may serve as a novel therapeutic potential in the treatment of IBD.http://dx.doi.org/10.1080/19490976.2021.1968257inflammatory bowel diseasebutyrateneutrophilsneutrophil extracellular trapsinflammatory mediators |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Gengfeng Li Jian Lin Cui Zhang Han Gao Huiying Lu Xiang Gao Ruixin Zhu Zhitao Li Mingsong Li Zhanju Liu |
spellingShingle |
Gengfeng Li Jian Lin Cui Zhang Han Gao Huiying Lu Xiang Gao Ruixin Zhu Zhitao Li Mingsong Li Zhanju Liu Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease Gut Microbes inflammatory bowel disease butyrate neutrophils neutrophil extracellular traps inflammatory mediators |
author_facet |
Gengfeng Li Jian Lin Cui Zhang Han Gao Huiying Lu Xiang Gao Ruixin Zhu Zhitao Li Mingsong Li Zhanju Liu |
author_sort |
Gengfeng Li |
title |
Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease |
title_short |
Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease |
title_full |
Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease |
title_fullStr |
Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease |
title_full_unstemmed |
Microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease |
title_sort |
microbiota metabolite butyrate constrains neutrophil functions and ameliorates mucosal inflammation in inflammatory bowel disease |
publisher |
Taylor & Francis Group |
series |
Gut Microbes |
issn |
1949-0976 1949-0984 |
publishDate |
2021-01-01 |
description |
Host-microbial cross-talk plays a crucial role in maintenance of gut homeostasis. However, how microbiota-derived metabolites, e.g., butyrate, regulate functions of neutrophils in the pathogenesis of inflammatory bowel disease (IBD) remains elusive. We sought to investigate the effects of butyrate on IBD neutrophils and elucidate the therapeutic potential in regulating mucosal inflammation. Peripheral neutrophils were isolated from IBD patients and healthy donors, and profiles of proinflammatory cytokines and chemokines were determined by qRT-PCR and ELISA, respectively. The migration and release of neutrophil extracellular traps (NETs) were studied by a Transwell model and immunofluorescence, respectively. The in vivo role of butyrate in regulating IBD neutrophils was evaluated in a DSS-induced colitis model in mice. We found that butyrate significantly inhibited IBD neutrophils to produce proinflammatory cytokines, chemokines, and calprotectins. Blockade of GPCR signaling with pertussis toxin (PTX) did not interfere the effects whereas pan-histone deacetylase (HDAC) inhibitor, trichostatin A (TSA) effectively mimicked the role of butyrate. Furthermore, in vitro studies confirmed that butyrate suppressed neutrophil migration and formation of NETs from both CD and UC patients. RNA sequencing analysis revealed that the immunomodulatory effects of butyrate on IBD neutrophils were involved in leukocyte activation, regulation of innate immune response and response to oxidative stress. Consistently, oral administration of butyrate markedly ameliorated mucosal inflammation in DSS-induced murine colitis through inhibition of neutrophil-associated immune responses such as proinflammatory mediators and NET formation. Our data thus reveal that butyrate constrains neutrophil functions and may serve as a novel therapeutic potential in the treatment of IBD. |
topic |
inflammatory bowel disease butyrate neutrophils neutrophil extracellular traps inflammatory mediators |
url |
http://dx.doi.org/10.1080/19490976.2021.1968257 |
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