Mechanisms of Casein-Derived Immunomodulatory Peptides Maintaining Immune Homeostasis via Regulating Gut Microbiota in a Cyclophosphamide-Induced Mouse Model

IF 6.2 1区农林科学 Q1 AGRICULTURE, MULTIDISCIPLINARY

Journal of Agricultural and Food Chemistry Pub Date : 2025-09-24 DOI:10.1021/acs.jafc.5c07986

Siyi Li, Zichen Li, Yanfeng Tuo, Guangqing Mu, Shujuan Jiang

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Abstract

Two immunomodulatory signature peptides (PFPEVFG and SPAQILQW) were obtained from casein hydrolysates produced by Kluyveromyces marxianus JY-1 in our previous studies with the aid of virtual screening. However, their mechanisms for improving the composition of the gut microbiota in immunosuppressed mice remain unknown. The aim of this study was to reveal the mechanisms of immunomodulation and improvement of gut microbiota composition mediated by the casein peptides PFPEVFG and SPAQILQW through a cyclophosphamide (Cy)-induced immunosuppression and intestinal mucosal injury mouse model. The casein peptides PFPEVFG and SPAQILQW reversed Cy-induced intestinal structural damage and could correct for Cy-induced intestinal flora disorders. Importantly, fecal microbiota transplantation (FMT) confirmed that the casein peptides PFPEVFG and SPAQILQW attenuate immunosuppression by targeting participation in the dynamic balance of the gut microbiota. These results indicated that the casein peptides PFPEVFG and SPAQILQW have the potential to be used as natural medicines for the treatment of immunosuppression.

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酪蛋白来源的免疫调节肽通过调节肠道微生物群在环磷酰胺诱导小鼠模型中维持免疫稳态的机制

通过虚拟筛选，我们从马氏克卢维菌JY-1酪蛋白水解产物中获得了两个免疫调节特征肽PFPEVFG和SPAQILQW。然而，它们改善免疫抑制小鼠肠道微生物群组成的机制尚不清楚。本研究旨在通过环磷酰胺（Cy）诱导的免疫抑制和肠粘膜损伤小鼠模型，揭示酪蛋白肽PFPEVFG和SPAQILQW介导的免疫调节和肠道微生物群组成改善的机制。酪蛋白肽PFPEVFG和SPAQILQW可逆转cy诱导的肠道结构损伤，并可纠正cy诱导的肠道菌群紊乱。重要的是，粪便微生物群移植（FMT）证实了酪蛋白肽PFPEVFG和SPAQILQW通过靶向参与肠道微生物群的动态平衡来减轻免疫抑制。这些结果表明，酪蛋白肽PFPEVFG和SPAQILQW具有作为治疗免疫抑制的天然药物的潜力。

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来源期刊

Journal of Agricultural and Food Chemistry 农林科学-农业综合

CiteScore

9.90

自引率

8.20%

发文量

1375

审稿时长

2.3 months

期刊介绍： The Journal of Agricultural and Food Chemistry publishes high-quality, cutting edge original research representing complete studies and research advances dealing with the chemistry and biochemistry of agriculture and food. The Journal also encourages papers with chemistry and/or biochemistry as a major component combined with biological/sensory/nutritional/toxicological evaluation related to agriculture and/or food.