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The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease

Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in...

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Autores principales: Wang, Fangyan, Qian, Fanyu, Zhang, Qihao, Zhao, Jian, Cen, Jianke, Zhang, Jiamin, Zhou, Jinhui, Luo, Ming, Jia, Chang, Rong, Xing, Chu, Maoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309029/
https://www.ncbi.nlm.nih.gov/pubmed/37398673
http://dx.doi.org/10.3389/fimmu.2023.1124118
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author Wang, Fangyan
Qian, Fanyu
Zhang, Qihao
Zhao, Jian
Cen, Jianke
Zhang, Jiamin
Zhou, Jinhui
Luo, Ming
Jia, Chang
Rong, Xing
Chu, Maoping
author_facet Wang, Fangyan
Qian, Fanyu
Zhang, Qihao
Zhao, Jian
Cen, Jianke
Zhang, Jiamin
Zhou, Jinhui
Luo, Ming
Jia, Chang
Rong, Xing
Chu, Maoping
author_sort Wang, Fangyan
collection PubMed
description Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum (C. butyricum) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host’s inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD.
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spelling pubmed-103090292023-06-30 The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease Wang, Fangyan Qian, Fanyu Zhang, Qihao Zhao, Jian Cen, Jianke Zhang, Jiamin Zhou, Jinhui Luo, Ming Jia, Chang Rong, Xing Chu, Maoping Front Immunol Immunology Kawasaki disease (KD), an acute febrile systemic vasculitis in children, has become the leading cause of acquired heart disease in developed countries. Recently, the altered gut microbiota was found in KD patients during the acute phase. However, little is known about its characteristics and role in the pathogenesis of KD. In our study, an altered gut microbiota composition featured by the reduction in SCFAs-producing bacteria was demonstrated in the KD mouse model. Next, probiotic Clostridium butyricum (C. butyricum) and antibiotic cocktails were respectively employed to modulate gut microbiota. The use of C. butyricum significantly increased the abundance of SCFAs-producing bacteria and attenuated the coronary lesions with reduced inflammatory markers IL-1β and IL-6, but antibiotics depleting gut bacteria oppositely deteriorated the inflammation response. The gut leakage induced by dysbiosis to deteriorate the host’s inflammation was confirmed by the decreased intestinal barrier proteins Claudin-1, Jam-1, Occludin, and ZO-1, and increased plasma D-lactate level in KD mice. Mechanistically, SCFAs, the major beneficial metabolites of gut microbes to maintain the intestinal barrier integrity and inhibit inflammation, was also found decreased, especially butyrate, acetate and propionate, in KD mice by gas chromatography-mass spectrometry (GC-MS). Moreover, the reduced expression of SCFAs transporters, monocarboxylate transporter 1 (MCT-1) and sodium-dependent monocarboxylate transporter 1 (SMCT-1), was also shown in KD mice by western blot and RT-qPCR analyses. As expected, the decrease of fecal SCFAs production and barrier dysfunction were improved by oral C. butyricum treatment but was deteriorated by antibiotics. In vitro, butyrate, not acetate or propionate, increased the expression of phosphatase MKP-1 to dephosphorylate activated JNK, ERK1/2 and p38 MAPK against excessive inflammation in RAW264.7 macrophages. It suggests a new insight into probiotics and their metabolites supplements to treat KD. Frontiers Media S.A. 2023-06-15 /pmc/articles/PMC10309029/ /pubmed/37398673 http://dx.doi.org/10.3389/fimmu.2023.1124118 Text en Copyright © 2023 Wang, Qian, Zhang, Zhao, Cen, Zhang, Zhou, Luo, Jia, Rong and Chu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Wang, Fangyan
Qian, Fanyu
Zhang, Qihao
Zhao, Jian
Cen, Jianke
Zhang, Jiamin
Zhou, Jinhui
Luo, Ming
Jia, Chang
Rong, Xing
Chu, Maoping
The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease
title The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease
title_full The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease
title_fullStr The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease
title_full_unstemmed The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease
title_short The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease
title_sort reduced scfa-producing gut microbes are involved in the inflammatory activation in kawasaki disease
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10309029/
https://www.ncbi.nlm.nih.gov/pubmed/37398673
http://dx.doi.org/10.3389/fimmu.2023.1124118
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