Indole-3-Propionic Acid, a Functional Metabolite of Clostridium sporogenes, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation

Clostridium sporogenes (C. sporogenes), as a potential probiotic, metabolizes tryptophan and produces an anti-inflammatory metabolite, indole-3-propionic acid (IPA). Herein, we studied the effects of C. sporogenes and its bioactive metabolite,...

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Autores principales:	Lei Du, Renli Qi, Jing Wang, Zuohua Liu, Zhenlong Wu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>C. sporogenes</i> muscle inflammation indole-3-propionic acid miR-26a-2-3p IL-1β Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/799f60784f9e44c0a894329e8e8bf5bf
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spelling	oai:doaj.org-article:799f60784f9e44c0a894329e8e8bf5bf2021-11-25T17:56:37ZIndole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation10.3390/ijms2222124351422-00671661-6596https://doaj.org/article/799f60784f9e44c0a894329e8e8bf5bf2021-11-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/22/12435https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>Clostridium sporogenes</i> (<i>C. sporogenes</i>), as a potential probiotic, metabolizes tryptophan and produces an anti-inflammatory metabolite, indole-3-propionic acid (IPA). Herein, we studied the effects of <i>C. sporogenes</i> and its bioactive metabolite, IPA, on skeletal muscle development and chronic inflammation in mice. In the in vivo study, the muscle tissues and serum samples of mice with <i>C. sporogenes</i> supplementation were used to analyze the effects of <i>C. sporogenes</i> on muscle metabolism; the IPA content was determined by metabonomics and ELISA. In an in vitro study, C2C12 cells were exposed to lipopolysaccharide (LPS) alone or LPS + IPA to verify the effect of IPA on muscle cell inflammation by transcriptome, and the involved mechanism was revealed by different functional assays. We observed that <i>C. sporogenes</i> colonization significantly increased the body weight and muscle weight gain, as well as the myogenic regulatory factors’ (MRFs) expression. In addition, <i>C. sporogenes</i> significantly improved host IPA content and decreased pro-inflammatory cytokine levels in the muscle tissue of mice. Subsequently, we confirmed that IPA promoted C2C12 cells’ proliferation by activating MRF signaling. IPA also effectively protected against LPS-induced C2C12 cells inflammation by activating Pregnane X Receptor and restoring the inhibited miR-26a-2-3p expression. miR-26a-2-3p serves as a novel muscle inflammation regulatory factor that could directly bind to the 3′-UTR of IL-1β, a key initiator factor in inflammation. The results suggested that <i>C. sporogenes</i> with its functional metabolite IPA not only helps muscle growth development, but also protects against inflammation, partly by the IPA/ miR-26a-2-3p /IL-1β cascade.Lei DuRenli QiJing WangZuohua LiuZhenlong WuMDPI AGarticle<i>C. sporogenes</i>muscle inflammationindole-3-propionic acidmiR-26a-2-3pIL-1βBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 12435, p 12435 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>C. sporogenes</i> muscle inflammation indole-3-propionic acid miR-26a-2-3p IL-1β Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>C. sporogenes</i> muscle inflammation indole-3-propionic acid miR-26a-2-3p IL-1β Biology (General) QH301-705.5 Chemistry QD1-999 Lei Du Renli Qi Jing Wang Zuohua Liu Zhenlong Wu Indole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation
description	<i>Clostridium sporogenes</i> (<i>C. sporogenes</i>), as a potential probiotic, metabolizes tryptophan and produces an anti-inflammatory metabolite, indole-3-propionic acid (IPA). Herein, we studied the effects of <i>C. sporogenes</i> and its bioactive metabolite, IPA, on skeletal muscle development and chronic inflammation in mice. In the in vivo study, the muscle tissues and serum samples of mice with <i>C. sporogenes</i> supplementation were used to analyze the effects of <i>C. sporogenes</i> on muscle metabolism; the IPA content was determined by metabonomics and ELISA. In an in vitro study, C2C12 cells were exposed to lipopolysaccharide (LPS) alone or LPS + IPA to verify the effect of IPA on muscle cell inflammation by transcriptome, and the involved mechanism was revealed by different functional assays. We observed that <i>C. sporogenes</i> colonization significantly increased the body weight and muscle weight gain, as well as the myogenic regulatory factors’ (MRFs) expression. In addition, <i>C. sporogenes</i> significantly improved host IPA content and decreased pro-inflammatory cytokine levels in the muscle tissue of mice. Subsequently, we confirmed that IPA promoted C2C12 cells’ proliferation by activating MRF signaling. IPA also effectively protected against LPS-induced C2C12 cells inflammation by activating Pregnane X Receptor and restoring the inhibited miR-26a-2-3p expression. miR-26a-2-3p serves as a novel muscle inflammation regulatory factor that could directly bind to the 3′-UTR of IL-1β, a key initiator factor in inflammation. The results suggested that <i>C. sporogenes</i> with its functional metabolite IPA not only helps muscle growth development, but also protects against inflammation, partly by the IPA/ miR-26a-2-3p /IL-1β cascade.
format	article
author	Lei Du Renli Qi Jing Wang Zuohua Liu Zhenlong Wu
author_facet	Lei Du Renli Qi Jing Wang Zuohua Liu Zhenlong Wu
author_sort	Lei Du
title	Indole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation
title_short	Indole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation
title_full	Indole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation
title_fullStr	Indole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation
title_full_unstemmed	Indole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation
title_sort	indole-3-propionic acid, a functional metabolite of <i>clostridium sporogenes</i>, promotes muscle tissue development and reduces muscle cell inflammation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/799f60784f9e44c0a894329e8e8bf5bf
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Indole-3-Propionic Acid, a Functional Metabolite of <i>Clostridium sporogenes</i>, Promotes Muscle Tissue Development and Reduces Muscle Cell Inflammation

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