Interplay between Skin Sympathetic Nerve Activity and Gut Microbiota, the Neurocardiac Axis in Acute Coronary Syndrome

BACKGROUND Previous studies have linked gut dysbiosis to the acute coronary syndrome (ACS) and sympathetic nervous system disturbances. However, the relationship between skin sympathetic nerve activity (SKNA) and gut microbiota in ACS patients remains largely unexplored. We hypothesize that elevated SKNA may interact with specific microbial profiles in ACS. METHODS AND RESULTS Fifteen ACS patients with age- and sex-matched controls were enrolled in the cross-sectional study. Subjects with type 2 diabetes or on antibiotics, proton pump inhibitors, or metformin were excluded. Demographic and clinical data were recorded, and SKNA was measured by neuECG. Gut microbial profiles were analyzed by sequencing the V3-V4 region of the 16S rRNA gene. Significant differences in alpha diversity, including Chao 1 index and Faith’s phylogenetic diversity, were observed between the ACS and control groups ( P <0.001). Distinct beta diversity between the two groups was also identified using unweighted normalized UniFrac analysis ( P =0.001). Redundancy analysis and Mantel test revealed a significant relationship between SKNA and microbial profiles. Several butyrate-producing bacteria were decreased in the ACS group, while the genus Hungatella , a trimethylamine producer, showed a significant increase and was positively correlated with SKNA. Additionally, predicted microbial functional analysis indicated an elevation in branched-chain amino acid biosynthesis in the ACS group. CONCLUSIONS This study is the first to establish an association between SKNA and gut microbial profiles in ACS patients. SKNA can serve as a biomarker for ACS, offering a simple and non-invasive tool to explore the interaction between the nervous system and gut microbiota in cardiovascular diseases. Clinical Perspective WHAT IS NEW? The Skin sympathetic nerve activity (SKNA) is a novel and non-invasive recording of the sympathetic nervous system from the skin of patients. The NEW findings in our study from acute coronary syndrome (ACS) patients are (1) to establish the correlation between SKNA, heart rate variability and microbiota, (2) the Hungatella is correlated with SKNA and standard deviation of NN intervals (SDNN). WHAT ARE THE CLINICAL IMPLICATIONS? Since microbiota and sympathetic nervous system (SNS) might be essential factors of ACS, it is important to assess the abundance of microbiota and SNS activity for accurate management of ACS. The Hungatella , one of the microbiota involved in atherosclerotic cardiovascular disease, heart failure, inflammatory process, and anxiety disorder, might be the link between SNS and ACS. In our study, we prove the positive association between Hungatella and SKNA. Therefore, by checking the SKNA of patients with ACS, we might discover the SNS activity and also the underlying microbiota etiology of ACS. Then, it is critical and accurate to target Hungatella in ACS patients with high SKNA to reduce the risk of ACS.