# Therapeutic Potential of Irpex lacteus Polysaccharides in Lupus Nephritis: Insights From Gut Microbiota and Metabolomics Analysis in MRL/Lpr Mice

## TL;DR

Polysaccharides from Irpex lacteus may help treat lupus nephritis by reducing inflammation, improving kidney function, and reshaping gut microbes in mice.

## Contribution

This study reveals that Irpex lacteus polysaccharides modulate the gut microbiota-metabolism axis to treat lupus nephritis in MRL/lpr mice.

## Key findings

- PCP reduced autoantibodies, inflammation, and improved kidney function in MRL/lpr mice.
- PCP altered gut microbiota composition, increasing Firmicutes and Bacteroidota phyla and specific genera.
- PCP affected key metabolites involved in pathways like tryptophan and linoleic acid metabolism.

## Abstract

Polysaccharides from Irpex lacteus (PCP) were evaluated for their therapeutic effects on lupus nephritis (LN) in MRL/lpr mice. After 8‐week interventions with low‐ and high‐dose PCP, we systematically evaluated the therapeutic efficacy by measuring the levels of autoantibodies, the expression of inflammatory cytokines, and renal function‐related parameters. Finally, 16S rDNA gut microbiome sequencing with metabolomics analysis was used to explore the pharmacological mechanism of PCP intervention in LN. PCP could reverse the phenotype of MRL/lpr mice, reduce autoantibody levels, alleviate inflammatory responses, and improve renal function. Gut microbiome analysis found that PCP can improve gut microbiota composition and abundance of two phyla (Firmicutes, Bacteroidota) and five genera (Lachnospiraceae NK4A136 group, Alistipes, Butyricicoccus, Bacteroides, Lactobacillus), which play an important role in the process of PCP intervention on metabolism in MRL/lpr mice. UHPLC–MS untargeted metabolomics showed that PCP significantly affects multiple key differential metabolites, including Linoleic acid, L‐Phenylalanine, L‐Tyrosine, and 56 other metabolites. These metabolites are primarily involved in metabolic pathways such as tryptophan metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, tyrosine metabolism, linoleic acid metabolism, and arachidonic acid metabolism. Correlation analysis between gut microbiota and differential metabolites reveals a close relationship, suggesting that gut microbiota promoting host metabolism may be one of the mechanisms by which PCP treats LN. PCP alleviates LN by modulating the “microbiota‐metabolism axis,” reducing autoantibodies, inflammation, and renal damage, while reshaping gut microbiota and regulating key metabolic pathways.

Polysaccharides from Irpex lacteus alleviated kidney inflammatory response. PCP could reverse the phenotype of MRL/lpr mice, reduce autoantibody levels, alleviate inflammatory responses, and improve renal function. Improving the body's metabolism by gut microbes may be the possible mechanism of PCP in treating LN.