在益生菌混合物中发现的小分子代谢物乙酸色醇酯和乙酸酪醇酯可抑制炎症反应。

IF 4.7 3区 医学 Q2 IMMUNOLOGY Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2023-02-21 DOI:10.1159/000529782
Orit Malka, Ravit Malishev, Marina Bersudsky, Manikandan Rajendran, Mathumathi Krishnamohan, Jakeer Shaik, Daniel A Chamovitz, Evgeni Tikhonov, Eliya Sultan, Omry Koren, Ron N Apte, Benyamin Rosental, Elena Voronov, Raz Jelinek
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引用次数: 0

摘要

益生菌发酵食品被认为有助于人类健康,但目前普遍缺乏确凿证据证明它们具有推定的系统治疗功效。在这里,我们报告了由益生菌牛奶发酵酵母菌 Kluyveromyces marxianus 分泌的小分子代谢物醋酸色酚和醋酸酪醇可抑制高炎症反应(如 "细胞因子风暴")。利用 LPS 诱导的高炎症模型进行的体内和体外综合分析表明,串联添加的这些分子对小鼠的发病率、实验室参数和死亡率有显著影响。具体来说,我们观察到促炎细胞因子 IL-6、IL-1α、IL-1β 和 TNF-α 的水平有所降低,活性氧也有所减少。重要的是,醋酸色醇和醋酸酪醇并没有完全抑制促炎细胞因子的生成,而是使其浓度恢复到基线水平,从而维持了包括吞噬作用在内的核心免疫功能。乙酸色醇酯和乙酸酪醇酯的抗炎作用是通过下调 TLR4、IL-1R 和 TNFR 信号通路以及增加 A20 的表达,从而抑制 NF-kB。总之,这项研究揭示了在益生菌混合物中发现的小分子抗炎特性的现象学和分子细节,指出了针对严重炎症的潜在治疗途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Tryptophol Acetate and Tyrosol Acetate, Small-Molecule Metabolites Identified in a Probiotic Mixture, Inhibit Hyperinflammation.

Probiotic fermented foods are perceived as contributing to human health; however, solid evidence for their presumptive therapeutic systemic benefits is generally lacking. Here we report that tryptophol acetate and tyrosol acetate, small-molecule metabolites secreted by the probiotic milk-fermented yeast Kluyveromyces marxianus, inhibit hyperinflammation (e.g., "cytokine storm"). Comprehensive in vivo and in vitro analyses, employing LPS-induced hyperinflammation models, reveal dramatic effects of the molecules, added in tandem, on mice morbidity, laboratory parameters, and mortality. Specifically, we observed attenuated levels of the proinflammatory cytokines IL-6, IL-1α, IL-1β, and TNF-α and reduced reactive oxygen species. Importantly, tryptophol acetate and tyrosol acetate did not completely suppress proinflammatory cytokine generation, rather brought their concentrations back to baseline levels, thus maintaining core immune functions, including phagocytosis. The anti-inflammatory effects of tryptophol acetate and tyrosol acetate were mediated through downregulation of TLR4, IL-1R, and TNFR signaling pathways and increased A20 expression, leading to NF-kB inhibition. Overall, this work illuminates phenomenological and molecular details underscoring anti-inflammatory properties of small molecules identified in a probiotic mixture, pointing to potential therapeutic avenues against severe inflammation.

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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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