Non-invasive ventilation restores the gut microbiota in rats with acute heart failure

Heart failure (HF) is an increasingly prevalent disease in humans; it induces multiple symptoms and damages health. Animal gut microbiota has critical roles in host health, which could be related to HF symptoms. Currently, several options are used to treat HF, including non-invasive ventilation (NIV). However, studies on gut microbiota responses to acute HF and associated treatments effects on gut communities in patients are scarce. Here, we examined gut microbiota variations in rats with acute HF and treated by NIV at the short (one week after treatments) and long-term periods (three month after treatments), respectively, by the high-throughput sequencing based on bacterial 16S rRNA gene. According to the comparison of alpha diversity of gut microbiota, we observed decreased gut microbiota richness and diversity in animals with acute HF comapred to normal individuals. Additionally, beta-diversity analysis also revealed significant alterations in the gut microbiota composition inducing by acute HF, as reflected by increased Firmicutes/Bacteroidetes (F/B) ratios and Proteobacteria enrichment. When we combined network analysis results and the null model, we observed decreased stability and elevated deterministic gut microbiota assemblies in animals with acute HF. Importantly, in short- and long-term periods, in acute HF rats, we showed that NIV recovered gut microbiota dysbiosis to normal states. Finally, we showed that considerable gut microbiota variations existed in rats with acute HF, that underlying microbiota mechanisms regulated these changes, and confirmed that NIV was suitable for HF treatment. In future studies, our findings should be validated with different model systems or clinical samples.

心力衰竭（Heart Failure, HF）是一类日益高发的人类疾病，可引发多种临床症状并损害机体健康。动物肠道菌群（gut microbiota）对宿主健康发挥着关键调控作用，其功能状态或与HF的发病症状密切相关。目前临床针对HF的治疗手段包含无创通气（non-invasive ventilation, NIV）等多种方案，但现有研究中，关于急性HF患者的肠道菌群应答特征，以及相关治疗手段对患者肠道菌群群落的影响的相关报道仍较为匮乏。本研究依托基于细菌16S rRNA基因的高通量测序技术，分别在短期（治疗后1周）与长期（治疗后3个月）两个时间维度，检测了急性HF大鼠经NIV治疗后的肠道菌群变化情况。通过对肠道菌群α多样性的比较分析，我们发现急性HF模型大鼠的肠道菌群丰富度与多样性均显著低于正常对照个体。此外，β多样性分析同样揭示了急性HF诱导的肠道菌群组成发生显著改变，具体体现为厚壁菌门/拟杆菌门（Firmicutes/Bacteroidetes, F/B）比值升高以及变形菌门（Proteobacteria）的菌群富集现象。当结合网络分析结果与零模型（null model）开展联合分析时，我们观察到急性HF模型大鼠的肠道菌群稳定性下降，且确定性菌群组装过程显著增强。值得注意的是，在短期与长期干预阶段，NIV均能够使急性HF大鼠的肠道菌群失调恢复至正常生理状态。最后，本研究证实急性HF大鼠存在显著的肠道菌群紊乱，其背后存在相应的菌群调控机制，并确认NIV适用于HF的临床治疗。未来的相关研究中，本研究的发现需通过不同的模型系统或临床样本进行进一步验证。