Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
Genome Med. 2024 Feb 8;16(1):27. doi: 10.1186/s13073-024-01296-6.
Interactions between the gut microbiota, diet, and host metabolism contribute to the development of cardiovascular disease, but a firm link between disease-specific gut microbiota alterations and circulating metabolites is lacking.
We performed shot-gun sequencing on 235 samples from 166 HF patients and 69 healthy control samples. Separate plasma samples from healthy controls (n = 53) were used for the comparison of imidazole propionate (ImP) levels. Taxonomy and functional pathways for shotgun sequencing data was assigned using MetaPhlAn3 and HUMAnN3 pipelines.
Here, we show that heart failure (HF) is associated with a specific compositional and functional shift of the gut microbiota that is linked to circulating levels of the microbial histidine-derived metabolite ImP. Circulating ImP levels are elevated in chronic HF patients compared to controls and associated with HF-related gut microbiota alterations. Contrary to the microbiota composition, ImP levels provide insight into etiology and severity of HF and also associate with markers of intestinal permeability and systemic inflammation.
Our findings establish a connection between changes in the gut microbiota, the presence, etiology, and severity of HF, and the gut-microbially produced metabolite ImP. While ImP appears promising as a circulating biomarker reflecting gut dysbiosis related to HF, further studies are essential to demonstrate its causal or contributing role in HF pathogenesis.
NCT02637167, registered December 22, 2015.
肠道微生物群、饮食和宿主代谢之间的相互作用导致了心血管疾病的发生，但特定的肠道微生物群改变与循环代谢物之间的确切联系尚不清楚。
我们对 166 名 HF 患者和 69 名健康对照样本中的 235 个样本进行了鸟枪法测序。健康对照者（n=53）的单独血浆样本用于比较亚精胺丙酸（ImP）水平。使用 MetaPhlAn3 和 HUMAnN3 管道对鸟枪法测序数据的分类和功能途径进行了分配。
在这里，我们表明心力衰竭（HF）与肠道微生物群的特定组成和功能转变相关，这种转变与微生物组衍生的代谢物 ImP 的循环水平有关。与对照组相比，慢性 HF 患者的循环 ImP 水平升高，并且与 HF 相关的肠道微生物群改变相关。与微生物群组成相反，ImP 水平提供了对 HF 的病因学和严重程度的深入了解，并且与肠道通透性和全身炎症的标志物相关。
我们的研究结果确立了肠道微生物群的变化、HF 的存在、病因和严重程度以及肠道微生物群产生的代谢物 ImP 之间的联系。虽然 ImP 作为反映与 HF 相关的肠道菌群失调的循环生物标志物具有很大的前景，但进一步的研究对于证明其在 HF 发病机制中的因果或促成作用至关重要。
NCT02637167，2015 年 12 月 22 日注册。
