Systolic heart failure, gut microbiome, multi-omics dataset

Chronic systolic heart failure (HF) is a prevalent and morbid disease with marked variability in its progression and response to therapies. The gut microbiome has been hypothesized to contribute to HF pathophysiology, but clinical studies exploring potential relationships are limited.Our study objective was to investigate gut microbiome alterations in chronic systolic HF and their associations with host metabolites, immune responses, and disease severity using multi-omics profiling.We analyzed the gut microbiome in a cohort of adults with chronic systolic HF caused by non-ischemic cardiomyopathy (<i>n</i>=59) using multi-omics profiling (including microbiome metagenomics, cytokine profiling, untargeted metabolomics, targeted lipidomics, and targeted microbial metabolite profiling) and, in some cases, longitudinal sampling. Comparisons were made with healthy subjects (<i>n</i>=50) and associations with metabolites, inflammatory markers, and HF severity were evaluated.We found that the anti-inflammatory probiotic <i>Bifidobacterium</i> and the associated short chain fatty acid-producing metabolic pathways were depleted in the chronic HF cohort. We also discovered HF-specific microbiome-host immunome interactions. In addition to identifying several taxa and microbial pathways broadly associated with HF disease severity, we identified significant associations between <i>Bifidobacterium</i> and clinical HF improvement over time. Gut microbiome-host multi-omic data integration revealed a close association between <i>Bifidobacterium</i> and the circulating metabolite indole-3-propionic acid, which was previously implicated in cardiovascular physiology, pointing to potential mechanisms through which <i>Bifidobacterium</i> may affect chronic HF physiology.Our findings reveal profound gut microbiome shifts in chronic systolic HF with potential systemic host effects. We also identify <i>Bifidobacterium</i> as a potential biomarker for chronic HF trajectory and suggest novel microbiome-based therapeutic strategies.

慢性收缩性心力衰竭（HF）是一类高患病率且高致残性的疾病，其病程进展及治疗应答均存在显著异质性。肠道菌群被推测参与心力衰竭的病理生理过程，但目前探索二者潜在关联的临床研究仍较为有限。本研究旨在通过多组学分析，探究慢性收缩性心力衰竭患者的肠道菌群改变及其与宿主代谢物、免疫应答及疾病严重程度的关联。本研究针对59例由非缺血性心肌病引发的慢性收缩性心力衰竭成人队列，采用多组学分析（包括宏基因组学、细胞因子谱分析、非靶向代谢组学、靶向脂质组学及靶向微生物代谢物谱分析）开展肠道菌群研究，部分样本还进行了纵向采样；并以50名健康受试者作为对照，评估了肠道菌群与代谢物、炎症标志物及心力衰竭严重程度的关联。研究发现，慢性心力衰竭队列中，具有抗炎作用的益生菌双歧杆菌（Bifidobacterium）及其相关的短链脂肪酸生成代谢通路均呈现丰度降低。本研究还揭示了心力衰竭特异性的菌群-宿主免疫组互作关系。除鉴定出多种与心力衰竭严重程度显著相关的菌属及微生物通路外，本研究还发现双歧杆菌丰度与随时间推移的心力衰竭临床改善存在显著关联。通过整合肠道菌群-宿主多组学数据，本研究发现双歧杆菌与循环代谢物吲哚-3-丙酸（indole-3-propionic acid）存在紧密关联；该代谢物此前已被证实与心血管生理功能相关，这为双歧杆菌影响慢性收缩性心力衰竭病理生理的潜在机制提供了线索。本研究结果揭示了慢性收缩性心力衰竭患者中存在显著的肠道菌群改变，并伴随潜在的全身性宿主效应；同时，本研究鉴定出双歧杆菌可作为慢性心力衰竭病程轨迹的潜在生物标志物，并提出了基于菌群的新型治疗策略。