Gut microbiota-derived lactate is associated with disrupted cardiac circadian rhythms in alcoholic heart disease
Year: 2026
Type: article
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.
Source: npj Biofilms and Microbiomes
Authors: Wei Siang, Lin Wenji, Zhao Yiji, Feng Yan, Lai Ren
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,290
Award: G2443546580
OpenAlex ID: W7135034840
