Cited by 88Muscle Physiology and DisordersGut microbiota and healthProbiotics and Fermented Foods

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

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Du, Lei, Qi, Renli, Wang, Jing, Liu, Zuohua, Wu, Zhenlong·2021·International Journal of Molecular Sciences

Abstract

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, IPA, on skeletal muscle development and chronic inflammation in mice. In the in vivo study, the muscle tissues and serum samples of mice with C. sporogenes supplementation were used to analyze the effects of C. sporogenes 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 C. sporogenes colonization significantly increased the body weight and muscle weight gain, as well as the myogenic regulatory factors’ (MRFs) expression. In addition, C. sporogenes 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 C. sporogenes 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.

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Authors
Du, L., Qi, R., Wang, J., Liu, Z., & Wu, Z.
Affiliations
  • Chongqing Academy of Animal Science (CN)
  • State Key Laboratory of Animal Nutrition (CN)
Corresponding author
  • Liu, Zuohua
  • Wu, Zhenlong
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-11-18
Volume
22
Issue
22
Pages
12435
ISSN
1422-0067 (ISSN-L)
OpenAlex
W3212098597
Cited by
87
References
36
Citations by year
2026: 21 · 2025: 23 · 2024: 22 · 2023: 12 · 2022: 9
FWCI
3.45
Type
journal article
Language
en
Open access
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Performance Reward and Guidance Project of Chongqing (cstc2019jxjl00008)
  • National Natural Science Foundation of China (No. 31625025, 31572410, 31572412, 31272450, 31272451)
  • Agricultural Development Program of Chongqing (19513)
  • National Key R&D Program of China (2018YFD0500404)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
Keywords
indole-3-propionic acid, Clostridium sporogenes, tryptophan metabolism, probiotics, skeletal muscle development, muscle inflammation, pregnane X receptor, IL-1β, myogenic regulatory factors, C2C12 myoblasts, lipopolysaccharide-induced inflammation, gut microbiota
MeSH terms
Gastrointestinal Microbiome, Pregnane X Receptor, Animals, Cell Line, Clostridium, Indoles, Inflammation, Lipopolysaccharides, Male, Mice, Inbred C57BL, Propionates, Tryptophan, Signal Transduction, Muscle, Skeletal, Gene Expression Regulation, Developmental, Probiotics, 3' Untranslated Regions, Gene Expression Profiling, Muscle Development, Muscle Cells, MicroRNAs, Mice, Interleukin-1beta, Transcriptome

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