Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury

Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbio...

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Autores principales:	Zhiyuan Chen, Bin Wang, Jiali Dong, Yuan Li, Shuqin Zhang, Xiaozhou Zeng, Huiwen Xiao, Saijun Fan, Ming Cui
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	radiation-induced cardiopulmonary injury gut microbiota metabolites imidazole propionate pyroptosis <span style="font-variant: small-caps">l</span>-histidine Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/58fe2839ffec4f54b546f6116e7a6233
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spelling	oai:doaj.org-article:58fe2839ffec4f54b546f6116e7a62332021-11-11T16:54:11ZGut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury10.3390/ijms2221114361422-00671661-6596https://doaj.org/article/58fe2839ffec4f54b546f6116e7a62332021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11436https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived <span style="font-variant: small-caps;">l-</span>Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of <span style="font-variant: small-caps;">l</span>-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. <span style="font-variant: small-caps;">l</span>-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. <span style="font-variant: small-caps;">l</span>-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of <span style="font-variant: small-caps;">l</span>-Histidine, accumulated in peripheral blood and lung tissues following <span style="font-variant: small-caps;">l</span>-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced <span style="font-variant: small-caps;">l</span>-Histidine and ImP are promising radioprotective agents.Zhiyuan ChenBin WangJiali DongYuan LiShuqin ZhangXiaozhou ZengHuiwen XiaoSaijun FanMing CuiMDPI AGarticleradiation-induced cardiopulmonary injurygut microbiota metabolitesimidazole propionatepyroptosis<span style="font-variant: small-caps">l</span>-histidineBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11436, p 11436 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	radiation-induced cardiopulmonary injury gut microbiota metabolites imidazole propionate pyroptosis <span style="font-variant: small-caps">l</span>-histidine Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	radiation-induced cardiopulmonary injury gut microbiota metabolites imidazole propionate pyroptosis <span style="font-variant: small-caps">l</span>-histidine Biology (General) QH301-705.5 Chemistry QD1-999 Zhiyuan Chen Bin Wang Jiali Dong Yuan Li Shuqin Zhang Xiaozhou Zeng Huiwen Xiao Saijun Fan Ming Cui Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
description	Radiation-induced cardiopulmonary injuries are the most common and intractable side effects that are entwined with radiotherapy for thorax cancers. However, the therapeutic options for such complications have yielded disappointing results in clinical applications. Here, we reported that gut microbiota-derived <span style="font-variant: small-caps;">l-</span>Histidine and its secondary metabolite imidazole propionate (ImP) fought against radiation-induced cardiopulmonary injury in an entiric flora-dependent manner in mouse models. Local chest irradiation decreased the level of <span style="font-variant: small-caps;">l</span>-Histidine in fecal pellets, which was increased following fecal microbiota transplantation. <span style="font-variant: small-caps;">l</span>-Histidine replenishment via an oral route retarded the pathological process of lung and heart tissues and improved lung respiratory and heart systolic function following radiation exposure. <span style="font-variant: small-caps;">l</span>-Histidine preserved the gut bacterial taxonomic proportions shifted by total chest irradiation but failed to perform radioprotection in gut microbiota-deleted mice. ImP, the downstream metabolite of <span style="font-variant: small-caps;">l</span>-Histidine, accumulated in peripheral blood and lung tissues following <span style="font-variant: small-caps;">l</span>-Histidine replenishment and protected against radiation-induced lung and heart toxicity. Orally gavaged ImP could not enter into the circulatory system in mice through an antibiotic cocktail treatment. Importantly, ImP inhibited pyroptosis to nudge lung cell proliferation after radiation challenge. Together, our findings pave a novel method of protection against cardiopulmonary complications intertwined with radiotherapy in pre-clinical settings and underpin the idea that gut microbiota-produced <span style="font-variant: small-caps;">l</span>-Histidine and ImP are promising radioprotective agents.
format	article
author	Zhiyuan Chen Bin Wang Jiali Dong Yuan Li Shuqin Zhang Xiaozhou Zeng Huiwen Xiao Saijun Fan Ming Cui
author_facet	Zhiyuan Chen Bin Wang Jiali Dong Yuan Li Shuqin Zhang Xiaozhou Zeng Huiwen Xiao Saijun Fan Ming Cui
author_sort	Zhiyuan Chen
title	Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
title_short	Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
title_full	Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
title_fullStr	Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
title_full_unstemmed	Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury
title_sort	gut microbiota-derived <span style="font-variant: small-caps">l</span>-histidine/imidazole propionate axis fights against the radiation-induced cardiopulmonary injury
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/58fe2839ffec4f54b546f6116e7a6233
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Gut Microbiota-Derived <span style="font-variant: small-caps">l</span>-Histidine/Imidazole Propionate Axis Fights against the Radiation-Induced Cardiopulmonary Injury

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