肠道微生物群衍生的乳酸与酒精性心脏病患者的昼夜节律紊乱有关
Gut microbiota-derived lactate is associated with disrupted cardiac circadian rhythms in alcoholic heart disease.
摘要(中文译文)
酒精性心脏病（AHD）涉及肠道菌群失调、代谢紊乱和昼夜节律紊乱，但它们之间的相互联系仍不清楚。我们利用小鼠AHD模型，整合了超声心动图、代谢组学、心脏转录组学和16S rRNA测序来研究酒精诱导的病理变化。该研究评估了膳食纤维和乙酸盐干预在恢复肠道菌群平衡、乳酸稳态和昼夜节律基因表达方面的潜力。统计分析包括相关性网络、受试者工作特征（ROC）曲线和通路富集分析。慢性酒精摄入导致肠道菌群失调，其特征为嗜黏蛋白阿克曼菌（Akkermansia muciniphila）过度生长以及肠道乳杆菌（Lactobacillus intestinalis）和嗜酸拟杆菌（Bacteroides acidifaciens）耗竭。该状态与高乳酸血症分数、心肌功能障碍相关，表现为射血分数降低和心脏纤维化。转录组分析揭示了昼夜节律相关基因的严重失调，包括BHLHE41、NFIL3和PER2。干预措施改善了微生物多样性，降低了乳酸水平，并通过乳酸-昼夜节律通路成功调控了心脏相关指标。ROC分析验证了BHLHE41、NFIL3和PER2作为高精度生物标志物（AUC > 0.85）。我们的研究揭示了AHD中的肠-心轴，其中微生物来源的乳酸与昼夜节律紊乱相关联，加重疾病。膳食纤维和乙酸盐是有前景的疗法，可重新平衡代谢物并调节昼夜节律网络，为酒精相关心血管疾病提供了新的生物标志物和策略。
Abstract
Alcoholic Heart Disease (AHD) involves gut microbiota dysbiosis, metabolic disturbances, and circadian disruption, yet their interconnections remain unclear. Using a murine AHD model, we integrated echocardiography, metabolomics, cardiac transcriptomics, and 16S rRNA sequencing to investigate alcohol-induced pathology. It evaluated dietary fiber and acetate interventions for their potential to restore gut microbiota balance, lactate homeostasis, and circadian gene expression. Statistical analyses included correlation networks, receiver operating characteristic (ROC) curves, and pathway enrichment. Chronic alcohol consumption led to gut dysbiosis characterized by an overgrowth of Akkermansia muciniphila and a depletion of Lactobacillus intestinalisand and Bacteroides acidifaciens. This condition was associated with hyperlactatemia fraction, myocardial dysfunction, evidenced by a reduced revealed fraction and cardiac fibrosis. Transcriptomic analysis revealed strong dysregulation of circadian-related genes, including BHLHE41, NFIL3, and PER2. Interventions improved microbial diversity, reduced lactate levels, and successfully regulated cardiac related indicators through the lactate-circadian rhythm pathway. ROC analysis validated BHLHE41, NFIL3, and PER2 as high-accuracy biomarkers (AUC > 0.85). Our study reveals a gut‑heart axis in AHD where microbiota‑derived lactate links to circadian disruption, worsening disease. Dietary fiber and acetate are promising therapies that rebalance metabolites and modulate circadian networks, offering novel biomarkers and strategies for alcohol‑related cardiovascular disease.
如何引用
AMA
Wei Siang, Lin Wenji, Zhao Yiji, Feng Yan, Lai Ren. Gut microbiota-derived lactate is associated with disrupted cardiac circadian rhythms in alcoholic heart disease.. NPJ biofilms and microbiomes. 2026; doi:10.1038/s41522-026-00958-0.
APA
Wei Siang, Lin Wenji, Zhao Yiji, Feng Yan, Lai Ren (2026). Gut microbiota-derived lactate is associated with disrupted cardiac circadian rhythms in alcoholic heart disease.. NPJ biofilms and microbiomes. https://doi.org/10.1038/s41522-026-00958-0
GB/T 7714
Wei Siang, Lin Wenji, Zhao Yiji, Feng Yan, Lai Ren. Gut microbiota-derived lactate is associated with disrupted cardiac circadian rhythms in alcoholic heart disease.[J]. NPJ biofilms and microbiomes, 2026 doi:10.1038/s41522-026-00958-0.
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