Supplemental Digital Content is available in the text. Pulmonary arterial hypertension (PAH) is considered a disease of the pulmonary vasculature. Limited progress has been made in preventing or arresting progression of PAH despite extensive efforts. Our previous studies indicated that PAH could be considered a systemic disease since its pathology involves interplay of multiple organs. This, coupled with increasing implication of the gut and its microbiome in chronic diseases, led us to hypothesize that patients with PAH exhibit a distinct gut microbiome that contributes to, and predicts, the disease. Fecal microbiome of 18 type 1 PAH patients (mean pulmonary arterial pressure, 57.4, SD 16.7 mm Hg) and 13 reference subjects were compared by shotgun metagenomics to evaluate this hypothesis. Significant taxonomic and functional changes in microbial communities in the PAH cohort were observed. Pathways for the synthesis of arginine, proline, and ornithine were increased in PAH cohort compared with reference cohort. Additionally, groups of bacterial communities associated with trimethylamine/ trimethylamine N-oxide and purine metabolism were increased in PAH cohort. In contrast, butyrate-and propionate-producing bacteria such as Coprococcus, Butyrivibrio, Lachnospiraceae, Eubacterium, Akkermansia, and Bacteroides were increased in reference cohort. A random forest model predicted PAH from the composition of the gut microbiome with 83% accuracy. Finally, virome analysis showed enrichment of Enterococcal and relative depletion of Lactococcal phages in the PAH cohort. In conclusion, patients with PAH exhibit a unique microbiome profile that has the high predictive potential for PAH. This highlights previously unknown roles of gut bacteria in this disease and could lead to new therapeutic, diagnostic, or management paradigms for PAH.

中文翻译：

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肺动脉高压患者肠道微生物组的改变

补充数字内容在文本中可用。肺动脉高压 (PAH) 被认为是一种肺血管疾病。尽管做出了大量努力，但在预防或阻止 PAH 进展方面取得的进展有限。我们之前的研究表明 PAH 可以被认为是一种全身性疾病，因为它的病理学涉及多个器官的相互作用。再加上肠道及其微生物组对慢性疾病的影响越来越大，我们假设 PAH 患者表现出独特的肠道微生物组，有助于并预测该疾病。通过鸟枪宏基因组学比较了 18 名 1 型 PAH 患者（平均肺动脉压，57.4，SD 16.7 mmHg）和 13 名参考受试者的粪便微生物组，以评估这一假设。观察到 PAH 队列中微生物群落的显着分类学和功能变化。与参考队列相比，PAH 队列中精氨酸、脯氨酸和鸟氨酸的合成途径增加。此外，在 PAH 队列中，与三甲胺/三甲胺 N-氧化物和嘌呤代谢相关的细菌群落群增加。相比之下，参考队列中产生丁酸和丙酸的细菌，如粪球菌、丁酸弧菌、毛螺菌科、真杆菌、阿克曼氏菌和拟杆菌增加。随机森林模型根据肠道微生物组的组成预测 PAH，准确度为 83%。最后，病毒组分析显示 PAH 队列中肠球菌的富集和乳球菌噬菌体的相对消耗。综上所述，PAH 患者表现出独特的微生物组特征，对 PAH 具有很高的预测潜力。这突出了肠道细菌在这种疾病中以前未知的作用，并可能为 PAH 带来新的治疗、诊断或管理范例。