The gut–heart axis and microbial diversity in post-COVID-19 vaccine myocardial infarction: insights into alpha and beta diversity shifts

Background: Emerging evidence implicates gut microbiota (GM) dysbiosis in myocardial infarction (MI) pathogenesis, especially in post-COVID-19 vaccination individuals. However, sex-specific patterns and the influence of vaccine type on GM diversity remain unexplored. The present cross-sectional study assessed alterations in GM alpha and beta diversity in post-COVID-19 vaccinated individuals with and without MI, stratified by sex and vaccine type. Methods: A cross-sectional study involved 40 participants: healthy males, healthy females, MI males, and MI females, further classified by vaccine type. Fecal samples underwent 16S rRNA sequencing. Alpha diversity indices [Observed species (Sobs), Chao1, ACE, Shannon, Simpson, and Coverage] and beta diversity (Bray–Curtis and UniFrac) were analyzed. Wilcoxon rank-sum test and Permutational Multivariate Analysis of Variance (PERMANOVA) were used for statistical evaluation ( P < 0.05). Results: Healthy females had significantly higher richness than males (Sobs: 431.60 ± 30.20 vs. 339.40 ± 35.05; P < 0.02). MI females showed reduced richness compared to healthy females (Sobs: 364.67 ± 48.02; P < 0.01). No significant differences were found between MI and healthy males ( P > 0.05). Among MI males, Pfizer recipients exhibited higher diversity than AstraZeneca recipients (Sobs: 396.57 ± 43.02 vs. 336.57 ± 30.19; P < 0.0131; Chao1: P < 0.0018; Shannon: P < 0.0292). Similar results were observed in MI females (Sobs: 400.00 ± 27.58 vs. 324.29 ± 30.43; P < 0.00022). Beta diversity revealed significant compositional shifts between MI and healthy individuals, as well as across sex and vaccine subgroups (PERMANOVA P < 0.05). Owing to the modest sample size ( n = 40) and subgroup stratification, these findings should be interpreted as exploratory and hypothesis-generating. Conclusion: The present pilot study provides early, hypothesis-generating insights into preliminary observations of a potential association between MI status, sex, COVID-19 vaccine platform, and GM diversity in a post-vaccination setting. The cross-sectional design, limited sample size, and absence of detailed demographic, clinical, and vaccination data (including the number of doses, booster status, timing relative to MI, and prior COVID-19 infection) preclude causal inference. Pfizer recipients had greater microbial richness, and MI females exhibited more pronounced dysbiosis, highlighting the need for hypothesis-generating observations that motivate future studies toward microbiome-informed approaches in the post-pandemic era. The cross-sectional design precludes any inference of causality or temporality regarding COVID-19 vaccination and MI.