Anti-Inflammatory Pathways Modulated by Microbial Polysaccharides from Euganean Thermal Muds in Zebrafish

TL;DR

This study explores how microbial polysaccharides from Italian thermal muds reduce inflammation in zebrafish by modulating key inflammatory pathways.

Contribution

The study identifies specific anti-inflammatory pathways modulated by microbial polysaccharides from Euganean thermal muds using transcriptome analysis in zebrafish.

Findings

M-PS treatment down-regulated key genes in inflammatory pathways like TNF-α and IL6–JAK–STAT.

Eleven up-regulated pathways showed reduced gene expression in M-PS-treated zebrafish larvae.

Seven down-regulated pathways, including E2F and G2M checkpoint, were identified.

Abstract

Thermal mud produced by spas of the Euganean Thermal District (Italy) has been used since ancient times for therapeutic purposes. Recently, the anti-inflammatory activity of microbial polysaccharides (M-PS), extracted from traditionally maturated muds, was demonstrated using the zebrafish model organism. However, the downstream signalling pathways regulated by M-PS remain largely unknown. In this study, to investigate the underlying mechanisms of inflammation resolution, we performed a transcriptome analysis on zebrafish larvae inflamed with copper sulphate and treated with M-PS. Our findings revealed that M-PS treatment down-regulated the expression of key genes involved in several inflammatory pathways. Gene Set Enrichment Analysis identified eleven up-regulated pathways (e.g., TNF-α signalling via NFκB, IL6–JAK–STAT signalling, p53 pathway, apoptosis, and interferon response) with components reduced in number and expression level in M-PS-treated larvae compared to the inflamed ones. Additionally, seven down-regulated pathways were identified (e.g., transcription factors E2F, MYC, and the G2M checkpoint). DEG-pseudotime analysis further confirmed the association of these genes with the pathways identified by GSEA. These results provide valuable insights into the anti-inflammatory properties of M-PS and the therapeutic potential of Euganean thermal muds for inflammatory diseases.

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