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

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.

• Authors: Lei Du, Renli Qi, Jing Wang, Zuohua Liu, Zhenlong Wu
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 22 (Nov 18 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 34830317 (Publication Type: Journal Article)

Chemical References

• 3' Untranslated Regions
• IL1B protein, mouse
• Indoles
• Interleukin-1beta
• Lipopolysaccharides
• MicroRNAs
• Mirn26 microRNA, mouse
• Nr1i2 protein, mouse
• Pregnane X Receptor
• Propionates
• Tryptophan
• 3-(indol-3-yl)propionic acid

Topics

• 3' Untranslated Regions
• Animals
• Cell Line
• Clostridium (metabolism)
• Gastrointestinal Microbiome (drug effects)
• Gene Expression Profiling
• Gene Expression Regulation, Developmental
• Indoles (metabolism, pharmacology)
• Inflammation (prevention & control)
• Interleukin-1beta (genetics, metabolism)
• Lipopolysaccharides (antagonists & inhibitors, pharmacology)
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (genetics, metabolism)
• Muscle Cells (cytology, drug effects, metabolism)
• Muscle Development (drug effects)
• Muscle, Skeletal (drug effects, metabolism, pathology)
• Pregnane X Receptor (genetics, metabolism)
• Probiotics (metabolism)
• Propionates (metabolism, pharmacology)
• Signal Transduction
• Transcriptome
• Tryptophan (metabolism)