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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Frontiers Media S.A.
2023-06-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1124118/full |
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| author | Fangyan Wang Fangyan Wang Fanyu Qian Fanyu Qian Qihao Zhang Qihao Zhang Jian Zhao Jian Zhao Jianke Cen Jianke Cen Jiamin Zhang Jiamin Zhang Jinhui Zhou Jinhui Zhou Ming Luo Ming Luo Chang Jia Chang Jia Xing Rong Xing Rong Maoping Chu Maoping Chu Maoping Chu |
| author_facet | Fangyan Wang Fangyan Wang Fanyu Qian Fanyu Qian Qihao Zhang Qihao Zhang Jian Zhao Jian Zhao Jianke Cen Jianke Cen Jiamin Zhang Jiamin Zhang Jinhui Zhou Jinhui Zhou Ming Luo Ming Luo Chang Jia Chang Jia Xing Rong Xing Rong Maoping Chu Maoping Chu Maoping Chu |
| author_sort | Fangyan Wang |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-13T05:26:48Z |
| format | Article |
| id | doaj.art-c6ac3dde564b46ce832d4f0a8bb4b3ee |
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| language | English |
| last_indexed | 2024-03-13T05:26:48Z |
| publishDate | 2023-06-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-c6ac3dde564b46ce832d4f0a8bb4b3ee2023-06-15T05:30:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-06-011410.3389/fimmu.2023.11241181124118The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki diseaseFangyan Wang0Fangyan Wang1Fanyu Qian2Fanyu Qian3Qihao Zhang4Qihao Zhang5Jian Zhao6Jian Zhao7Jianke Cen8Jianke Cen9Jiamin Zhang10Jiamin Zhang11Jinhui Zhou12Jinhui Zhou13Ming Luo14Ming Luo15Chang Jia16Chang Jia17Xing Rong18Xing Rong19Maoping Chu20Maoping Chu21Maoping Chu22Department of Pathophysiology, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, ChinaThe Research Institute of Microbiota and Host Inflammation-Related Diseases, Wenzhou Medical University, Wenzhou, ChinaPediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaDepartment of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, ChinaPediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, ChinaThe Research Institute of Microbiota and Host Inflammation-Related Diseases, Wenzhou Medical University, Wenzhou, ChinaSchool of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, ChinaThe Research Institute of Microbiota and Host Inflammation-Related Diseases, Wenzhou Medical University, Wenzhou, ChinaDepartment of Pathophysiology, School of Basic Medical Science, Wenzhou Medical University, Wenzhou, ChinaThe Research Institute of Microbiota and Host Inflammation-Related Diseases, Wenzhou Medical University, Wenzhou, ChinaPediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, ChinaPediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, ChinaPediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, ChinaPediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaChildren’s Heart Center, Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaPediatric Research Institute, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaKey Laboratory of Structural Malformations in Children of Zhejiang Province, Wenzhou, ChinaChildren’s Heart Center, Institute of Cardiovascular Development and Translational Medicine, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, ChinaKawasaki 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.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1124118/fullKawasaki diseasegut microbiotabutyrateSCFAsMAPKmacrophage |
| spellingShingle | Fangyan Wang Fangyan Wang Fanyu Qian Fanyu Qian Qihao Zhang Qihao Zhang Jian Zhao Jian Zhao Jianke Cen Jianke Cen Jiamin Zhang Jiamin Zhang Jinhui Zhou Jinhui Zhou Ming Luo Ming Luo Chang Jia Chang Jia Xing Rong Xing Rong Maoping Chu Maoping Chu Maoping Chu The reduced SCFA-producing gut microbes are involved in the inflammatory activation in Kawasaki disease Frontiers in Immunology Kawasaki disease gut microbiota butyrate SCFAs MAPK macrophage |
| 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 | Kawasaki disease gut microbiota butyrate SCFAs MAPK macrophage |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1124118/full |
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