# Liver–Microbiome Crosstalk Mediates the Protective Effects of Artemisinin in Clostridium perfringens Models

## TL;DR

Artemisinin helps reduce the effects of Clostridium perfringens infection in animals by improving immune and liver functions, though it doesn't significantly change gut bacteria.

## Contribution

Artemisinin's protective effects in C. perfringens models are mediated through liver-microbiome interactions, not by altering gut microbiota composition.

## Key findings

- Artemisinin modulated inflammatory and antioxidant responses in a tissue- and species-specific manner.
- Transcriptomic analysis showed ART affected liver genes related to detoxification and stress response.
- Microbiota shifts were subtle, with genus-level correlations to immune and detoxification genes.

## Abstract

Clostridium perfringens
is a multi‐host opportunistic pathogen whose plasmid‐encoded toxins cause gas gangrene, necrotic enteritis and enterotoxemia, resulting in substantial economic losses in animal husbandry. In light of antibiotic bans and the need for alternatives, we employed reverse network pharmacology to screen and in vitro validate artemisinin (ART), then assessed its efficacy in murine and rabbit infection models challenged with
C. perfringens
type F. ART treatment did not significantly affect body weight change or intestinal histopathological damage. However, it significantly modulated inflammatory cytokines and antioxidant parameters in a tissue‐ and species‐dependent manner. Specifically, ART increased serum TNF‐α in mice, decreased IL‐1β in rabbits and elevated IL‐10 in multiple tissues. In addition, ART enhanced hepatic SOD and T‐AOC in mice and reduced hepatic MDA in rabbits. Microbiota analysis revealed limited and subtle shifts in community structure following ART intervention. Transcriptomic analysis further indicated that ART treatment induced marked changes in hepatic gene expression, particularly involving detoxification, lipid metabolism and stress response pathways, with notable species‐specific differences in enrichment profiles. While correlation analysis suggested associations of Anaerotruncus with hepatic detoxification genes and Bacteroides with inflammation‐regulatory genes, these genus‐level findings are based on correlation only and should be interpreted with caution given the lack of significant changes in overall microbial community structure. Collectively, these results indicate that ART can modulate host inflammatory and antioxidant responses, but its impact on gut microbiota composition in
C. perfringens
infection models appears limited, and the biological significance of observed genus‐level associations remains to be elucidated.

Artemisinin mitigates
Clostridium perfringens
infection in mice and rabbits by modulating gut–liver crosstalk, leading to restored intestinal morphology, balanced microbiota composition and improved immunometabolic profiles.