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植物乳杆菌关键色氨酸代谢特征对芳烃受体激活及溃疡性结肠炎缓解作用的鉴定

Identification of the key tryptophan metabolic characteristics of Lactiplantibacillus plantarum for aryl hydrocarbon receptor activation and ulcerative colitis alleviation.

作者信息

Zuo Xuemei, Zhang Tingting, Dong Xueqian, Liu Jianjun, Liu Yang

机构信息

Shandong Food Ferment Industry & Design Institute, QiLu University of Technology (Shandong Academy of Sciences), Jinan 250013 China.

Shanghai Engineering Research Center of Food Microbiology, School of Health Science and Engineering, University of Shanghai for Science and Technology, Shanghai 200093 China.

出版信息

Food Res Int. 2025 Feb;203:115766. doi: 10.1016/j.foodres.2025.115766. Epub 2025 Jan 23.

DOI:10.1016/j.foodres.2025.115766
PMID:40022314
Abstract

Lactiplantibacillus plantarum can activate aryl hydrocarbon receptor (AHR) signaling in the gut by metabolizing tryptophan, thereby counteracting inflammation. However, the tryptophan metabolic characteristics of microorganisms are strain-specific and significantly influence their AHR-activating effects. In this study, four strains with different tryptophan metabolic profiles were screened, and a dextran sulfate sodium-induced colitis model was established in C57BL/6 mice. The key tryptophan metabolic characteristics of L. plantarum involved in AHR downstream signaling activation to alleviate colitis were explored. The results showed that strain SFFI50, characterized by poor tryptophan metabolism, and strain SFFI175, which produced high levels of IAA and ICA, did not alleviate colitis. Strain SFFI118, capable of metabolizing tryptophan to produce IAA, ICA, and ILA, could slightly restore mouse body weight, DAI, and IL-22 expression. L. plantarum SFFI23 significantly restored body weight, colon length, histopathological damage, and cytokine expression in mice. Moreover, it activated the downstream signaling of AHR, specifically CYP1A1, and repairs the intestinal barrier function. Targeted metabolomic analysis revealed a significant increase in indole-3-lactic acid (ILA) in the mouse intestine. Correlation analysis revealed a significant positive correlation between high ILA production of L. plantarum, CYP1A1 expression, intestinal barrier function restoration, ILA levels in vivo, and colitis alleviation. Therefore, we inferred that high ILA production is a key tryptophan metabolic characteristic of L. plantarum which activated AHR downstream signaling (such as CYP1A1, IL-22, and STAT3) to alleviate colitis. This study provides a theoretical basis for the development of personalized dietary interventions to improve gut health.

摘要

植物乳杆菌可通过代谢色氨酸激活肠道中的芳烃受体(AHR)信号通路,从而对抗炎症。然而,微生物的色氨酸代谢特征具有菌株特异性,并显著影响其AHR激活效果。本研究筛选了四株具有不同色氨酸代谢谱的菌株,并在C57BL/6小鼠中建立了葡聚糖硫酸钠诱导的结肠炎模型。探索了植物乳杆菌参与AHR下游信号激活以减轻结肠炎的关键色氨酸代谢特征。结果表明,色氨酸代谢较差的菌株SFFI50和产生高水平吲哚-3-乙酸(IAA)和吲哚-3-羧酸(ICA)的菌株SFFI175均不能减轻结肠炎。能够将色氨酸代谢产生IAA、ICA和吲哚-3-乳酸(ILA)的菌株SFFI118可略微恢复小鼠体重、疾病活动指数(DAI)和白细胞介素-22(IL-22)的表达。植物乳杆菌SFFI23显著恢复了小鼠的体重、结肠长度、组织病理学损伤和细胞因子表达。此外,它激活了AHR的下游信号,特别是细胞色素P450 1A1(CYP1A1),并修复了肠道屏障功能。靶向代谢组学分析显示小鼠肠道中吲哚-3-乳酸(ILA)显著增加。相关性分析显示植物乳杆菌高ILA产量、CYP1A1表达、肠道屏障功能恢复、体内ILA水平和结肠炎缓解之间存在显著正相关。因此,我们推断高ILA产量是植物乳杆菌的关键色氨酸代谢特征,其激活AHR下游信号(如CYP1A1、IL-22和信号转导和转录激活因子3(STAT3))以减轻结肠炎。本研究为开发改善肠道健康的个性化饮食干预措施提供了理论依据。

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