Kinetics of imidazole propionate from orally delivered histidine in mice and humans.

IF 7.8 1区 生物学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Moritz V Warmbrunn, Ilias Attaye, Anthony Horak, Rakhee Banerjee, William J Massey, Venkateshwari Varadharajan, Elena Rampanelli, Youling Hao, Sumita Dutta, Ina Nemet, Judith Aron-Wisnewsky, Karine Clément, Annefleur Koopen, Koen Wortelboer, Per-Olof Bergh, Mark Davids, Nadia Mohamed, E Marleen Kemper, Stanley Hazen, Albert K Groen, Daniel H van Raalte, Hilde Herrema, Fredrik Backhed, J Mark Brown, Max Nieuwdorp
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Abstract

Imidazole Propionate (ImP), a gut-derived metabolite from histidine, affects insulin signaling in mice and is elevated in type 2 diabetes (T2D). However, the source of histidine and the role of the gut microbiota remain unclear. We conducted an intervention study in mice and humans, comparing ImP kinetics in mice on a high-fat diet with varying histidine levels and antibiotics, and assessed ImP levels in healthy and T2D subjects with histidine supplementation. Results show that dietary histidine is metabolized to ImP, with antibiotic-induced gut microbiota suppression reducing ImP levels in mice. In contrast, oral histidine supplementation resulted in increases in circulating ImP levels in humans, whereas antibiotic treatment increased ImP levels, which was associated with a bloom of several bacterial genera that have been associated with ImP production, such as Lactobacilli. Our findings highlight the gut microbiota's crucial role in regulating ImP and the complexity of translating mouse models to humans.

小鼠和人类口服组氨酸咪唑丙酸盐的动力学。
组氨酸丙酸咪唑盐(ImP)是一种来自肠道的组氨酸代谢物,它会影响小鼠的胰岛素信号传导,并在 2 型糖尿病(T2D)中升高。然而,组氨酸的来源和肠道微生物群的作用仍不清楚。我们在小鼠和人类中进行了一项干预研究,比较了不同组氨酸水平的高脂饮食和抗生素在小鼠中的 ImP 动力学,并评估了补充组氨酸的健康和 T2D 受试者的 ImP 水平。结果显示,饮食中的组氨酸会代谢为 ImP,抗生素引起的肠道微生物群抑制会降低小鼠的 ImP 水平。相反,口服组氨酸补充剂会导致人体循环中的 ImP 水平升高,而抗生素治疗会增加 ImP 水平,这与乳酸杆菌等几种与 ImP 产生有关的细菌属大量繁殖有关。我们的研究结果凸显了肠道微生物群在调节 ImP 方面的关键作用,以及将小鼠模型转化为人类模型的复杂性。
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来源期刊
npj Biofilms and Microbiomes
npj Biofilms and Microbiomes Immunology and Microbiology-Microbiology
CiteScore
12.10
自引率
3.30%
发文量
91
审稿时长
9 weeks
期刊介绍: npj Biofilms and Microbiomes is a comprehensive platform that promotes research on biofilms and microbiomes across various scientific disciplines. The journal facilitates cross-disciplinary discussions to enhance our understanding of the biology, ecology, and communal functions of biofilms, populations, and communities. It also focuses on applications in the medical, environmental, and engineering domains. The scope of the journal encompasses all aspects of the field, ranging from cell-cell communication and single cell interactions to the microbiomes of humans, animals, plants, and natural and built environments. The journal also welcomes research on the virome, phageome, mycome, and fungome. It publishes both applied science and theoretical work. As an open access and interdisciplinary journal, its primary goal is to publish significant scientific advancements in microbial biofilms and microbiomes. The journal enables discussions that span multiple disciplines and contributes to our understanding of the social behavior of microbial biofilm populations and communities, and their impact on life, human health, and the environment.
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