Sodium Butyrate Attenuates Isoprenaline-Induced Myocardial Injury via Restoring the Gut-Heart Axis and Suppressing...

The gut-heart axis plays a role in cardiac injury due to the disruption of barriers, endotoxemia, and inflammatory signaling; yet, it is not clear whether sodium butyrate (SB) is capable of alleviating isoprenaline-induced myocardial injury through coordinated intestinal, microbial, and metabolic restoration. This study used male Sprague-Dawley rats, which were grouped into control, control + SB, isoprenaline (ISO)-induced myocardial injury, and ISO + SB groups. We evaluated cardiac biomarkers of injury, oxidative stress, histopathologic, intestinal barrier (16S rRNA sequencing), and serum metabolomics (LC-MS). SB treatment decreased serum cardiac troponin I, creatine kinase-MB, and lactate dehydrogenase; relieved oxidative stress; and lowered myocardial necrosis and fibrosis. It re-established colonic architecture, upregulated the expression of ZO-1 (zonula occludens-1) and claudin-1, and reduced endotoxin in the bloodstream. SB also prevented the production of proinflammatory cytokines such as TNF-α, IL-6, and IL-1β; cardiac TLR4; IκBα degradation; and NF-κB p 65 phosphorylation. In addition, SB altered the gut microbiota in favor of beneficial commensals, including Ligilactobacillus and Bifidobacterium, and reduced Desulfovibrio. It normalized key circulating metabolites and enriched cardiometabolic pathways, and the patterns of correlation suggested the coordinated remodeling of the microbiome-metabolome. These findings reveal that SB prevents myocardial injury caused by ISO through strengthening gut barrier protection, alleviating endotoxemia, inhibiting TLR4/NF-κB, and remodeling the microbiome-metabolome axis, indicating its potential for use as a gut-targeted cardioprotective intervention.