Dynamic remodeling of the gut microbiome and host responses after myocardial infarction revealed by longitudinal metaproteomics.

The gut microbiota is increasingly recognized as a key regulator of cardiovascular health; however, its functional dynamics following myocardial infarction (MI) remain poorly defined. While traditional sequencing approaches focus on microbial composition, they cannot capture real-time functional activity. In this study, we established a rat model of MI via permanent ligation of the left anterior descending artery and collected fecal samples from MI and sham-operated cohorts at baseline and Days 2, 7, and 14 post-surgery. High-resolution metaproteomics was applied to quantify microbial and host proteins, integrating functional annotation, differential expression, and weighted gene co-expression network analysis (WGCNA). We observed an acute, generalized decline in microbial diversity at Day 2 across both groups, indicative of a physiological response to surgical stress. Crucially, MI-specific divergence emerged during the subacute phase (Day 7) and persisted into recovery (Day 14). At Day 7, functional perturbations peaked in the MI group, significantly involving carbohydrate metabolism, nucleotide biosynthesis, and oxidative stress pathways, accompanied by taxonomic shifts including the depletion of Akkermansia and enrichment of Odoribacter and Muribaculum. Concurrently, host-derived proteins displayed time-dependent alterations in lipid catabolism and redox regulation. WGCNA revealed co-regulated protein modules linked to MI status and the recovery phase, reflecting highly synchronized host-microbiome responses. This time-resolved metaproteomic study demonstrates that following initial surgical stress, MI triggers dynamic, stage-specific alterations in gut microbial function and coordinated host responses, providing mechanistic insights into the gut-heart axis and suggesting potential microbiota-targeted strategies to promote post-MI recovery.