Aims: Circulating amino acid (AA) abnormalities serve as predictors of adverse outcomes in patients with heart failure (HF). However, the role of the gut microbiota in AA disturbances remains unknown. Thus, we investigated gut microbial functions and their associations with AA metabolic alterations in patients with HF.

Methods and Results: We performed whole-genome shotgun sequencing of fecal samples and mass spectrometry-based profiling of AAs in patients with compensated HF. Plasma levels of total essential AAs (EAAs) and histidine were significantly lower in patients with HF than in control subjects. HF patients also displayed increased and decreased abundance of gut microbial genes involved in the degradation and biosynthesis, respectively, of EAAs, including branched-chain AAs (BCAAs) and histidine. Importantly, a significant positive correlation was observed between the abundance of microbial genes involved in BCAA biosynthesis and plasma BCAA levels in patients with HF, but not in controls. Moreover, network analysis revealed that the depletion of Eubacterium and Prevotella, which harbor genes for BCAA and histidine biosynthesis, contributed to decreased abundance of microbial genes involved in the biosynthesis of those EAAs in patients with HF.

Conclusions: The present study demonstrated the relationship between gut microbiota and AA metabolic disturbances in patients with HF.

目标：循环氨基酸 (AA) 异常可作为心力衰竭 (HF) 患者不良结局的预测因子。然而，肠道微生物群在 AA 紊乱中的作用仍然未知。因此，我们研究了 HF 患者的肠道微生物功能及其与 AA 代谢改变的关联。

方法和结果：我们对代偿性 HF 患者的粪便样本进行了全基因组鸟枪法测序，并对 AA 进行了基于质谱的分析。心衰患者的血浆总必需氨基酸 (EAA) 和组氨酸水平显着低于对照组。HF 患者还表现出分别参与 EAA（包括支链 AA（BCAA）和组氨酸）降解和生物合成的肠道微生物基因丰度的增加和减少。重要的是，在 HF 患者中观察到参与 BCAA 生物合成的微生物基因的丰度与血浆 BCAA 水平之间存在显着的正相关，但在对照组中则没有。此外，网络分析表明，真杆菌 和 普雷沃泰拉含有 BCAA 和组氨酸生物合成基因，导致 HF 患者参与这些 EAA 生物合成的微生物基因丰度降低。

结论： 本研究证明了 HF 患者肠道微生物群与 AA 代谢紊乱之间的关系。