A Potential Probiotic for Diarrhea: Clostridium tyrobutyricum Protects Against LPS-Induced Epithelial Dysfunction via IL-22 Produced By Th17 Cells in the Ileum

Abstract

Probiotics are clinically used for diarrhea and inflammatory bowel diseases in both humans and animals. Previous studies have shown that Clostridium tyrobutyricum (Ct) protects against intestinal dysfunction, while its regulatory function in the gut needs further investigation and the related mechanisms are still not fully elucidated. This study aims to further verify the protective function of Ct and reveal its underlying mechanisms in alleviating diarrhea and intestinal inflammation. Ct inhibited LPS-induced diarrhea and intestinal inflammation in the ileum. IL-22 was identified and the protective role of Ct in the ileum presented an IL-22-dependent manner according to the transcriptomic analysis and in vivo interference mice experiments. The flow cytometric analysis of immune cells in the ileum showed that Ct enhanced the proportions of Th17 cells in response to LPS. The results of in situ hybridization further verified that Ct triggered Th17 cells to produce IL-22, which combined with IL-22RA1 expressed in the epithelial cells. Moreover, Ct was unable to enhance the levels of short-chain fatty acids (SCFAs) in the ileum, suggesting that the protective role of Ct in the ileum was independent of SCFAs. This study uncovered the role of Ct in alleviating diarrhea and inflammation with the mechanism of stimulating Th17 cells in the lamina propria to produce IL-22, highlighting its potential application as a probiotic for diarrhea and inflammation in the ileum.

Effects of Clostridium tyrobutyricum on Lipid Metabolism, Intestinal Barrier Function, and Gut Microbiota in Obese Mice Induced by High-Fat Diet

“…Our findings align with these previous reports and highlight that Ct intervention reduced lipid deposition in the liver by downregulating PPARγ expression and upregulating AMPK, ATGL, HSL, and PPARα expression. This validates the results of our previous transcriptomic data and is consistent with the research of Kershaw et al [ 24 , 36 ].…”

“…Our previous study on C. tyrobutyricum revealed its considerable high gastrointestinal tolerance and anti-inflammatory effect. Given that Ct was also linked to modifications in the expression of genes associated with hepatic lipid metabolism, we suspect that Ct treatment could alleviate obesity [ 24 ]. The present study offered novel evidence regarding the significant mitigating effect of C. tyrobutyricum intervention in lipid metabolic disorders brought on by the high-fat diet.…”

“…Transcriptome sequencing performed by our laboratory revealed that Ct can reverse metabolic processes, including the synthesis and breakdown of fatty acids. As evidenced by our Kyoto Encyclopedia of Genes and Genomes results, the adipocytokine signaling pathway was enriched for carnitine palmitoyltransferase-1 and acetyl-CoA carboxylase 2 (ACC2) [ 24 ]. In other words, Ct can play an essential role in host health by modulating intestinal immunity and may participate in regulating lipid metabolism.…”

Limosilactobacillus mucosae-derived extracellular vesicles modulates macrophage phenotype and orchestrates gut homeostasis in a diarrheal piglet model

“…Furthermore, although no statistical differences existed, the relative abundance of E. coli in the feces of diarrheal piglets was twice of that of healthy piglets. LPS is a classical virulence factor produced by E. coli that causes diarrhea 42 , 43 , and our KEGG functional analysis revealed that LPS biosynthesis was significantly higher in diarrheal newborn piglets than in healthy newborn piglets. The Fusobacteria are a small group of Gram-negative bacteria, of which Fusobacterium are commonly found in the digestive tract of humans and animals.…”

The role of Th17 cells in inflammatory bowel disease and the research progress

“…In addition, Clostridium can inhibit the release of the proinflammatory factor IL-17 through short-chain fatty acids (SCFAs), thereby reducing the differentiation of Th1 and Th17 cells ( 39 , 40 ). The mechanism by which SCFAs regulate T-cell differentiation includes the mTOR pathway, G-protein-coupled receptor signaling, and epigenome remodeling to promote Treg cell differentiation.…”