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Phytomedicine : international journal of phytotherapy and phytopharmacology · 2025

Phloretin alleviates Salmonella pullorum infection by modulating gut microbiota-derived 3-phenylpropionic acid and AhR/IL-22/STAT-3 axis.

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Ding Linlin, Li Qingjie, Qi Kaige, Chen Yonghui, Hu Na, Hu Sangyu, Fang Tianqi, Guan Shuang, Wang Jianfeng, Qiu Jiazhang, Deng Xuming, Xu Lei

Аннотация

BACKGROUND: Salmonella pullorum (S. pullorum) is an enteric pathogen that impairs growth performance, leading to substantial economic losses. Evidence demonstrates that the natural flavonoid phloretin can modulate gut microbiota functionality, and which underpins its therapeutic efficacy in ameliorating gastrointestinal disorders. However, the protective effects of phloretin against S. pullorum infections and underlying mechanisms remain unelucidated.

PURPOSE: This study aimed to elucidate the protective effects and mechanisms of phloretin in improving defense against S. pullorum infection by modulating gut microbiota in chicks.

METHODS: H&E staining, RT-qPCR and ELISA assays were used to assess the protective potentials of phloretin in S. pullorum-infected chicks. Then, 16S rRNA gene sequencing and untargeted metabolomics were employed to identify key microbiota and metabolites regulating the intestinal microenvironment. Moreover, fecal microbiota transplantation (FMT) and dietary metabolite supplementation were conducted to reshape the gut microbiota, elucidate the interaction between the microbiota and S. pullorum infection.

RESULTS: Phloretin treatment alleviated intestinal injury and enhanced growth performance in S. pullorum-infected chicks via improved intestinal barrier integrity, suppression of inflammatory responses, and restructuring of gut microbial composition. Additionally, these beneficial effects were also observed following FMT from phloretin-treated donors. Subsequent microbial and untargeted metabolomic analysis revealed that phloretin significantly enriched abundance of the functional bacterium Faecalibacterium, and the microbiota-derived phenylalanine metabolites 3-phenylpropionic acid (3-PPA). Importantly, 3-PPA supplementation attenuates S. pullorum-induced intestinal barrier damage and inflammation in chicks through modulation of the AhR/IL-22/STAT-3 signalling axis.

CONCLUSION: These findings provide new insights into the therapeutic potentials of phloretin for S. pullorum-infected chicks.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты