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Our previous study demonstrated increased skin sympathetic nerve activity (SKNA) in acute coronary syndrome (ACS) patients and its correlation with ventricular arrhythmias. In the current study, we explored specific gut microbial profiles and their relationships with SKNA in ACS patients. Fifteen ACS patients and age- and sex-matched controls were included in this cross-sectional study. Demographic and clinical data were recorded, and SKNA was measured by neuECG. The gut microbial profiles were analyzed by 16S rRNA gene sequencing of the V3-V4 region. Statistically significant differences in alpha diversity (including the Chao 1 index and Faith's phylogenetic diversity) and gut microbial composition were observed between the ACS and control groups. Redundancy analysis and the Mantel test revealed a significant relationship between SKNA and the microbial profiles. The abundance of butyrate-producing bacteria, including Lachnospira and Oscillibacter, was decreased in the ACS group, whereas the abundance of the genus Hungatella, a trimethylamine producer, significantly increased and was positively correlated with the abundance of SKNA. This study is the first to establish an association between SKNA and gut microbial profiles in ACS patients. SKNA may serve as a potential biomarker reflecting the interaction between the nervous system and gut microbiota in ACS.