Hermie J. M. Harmsen

Aims Despite treatment advancements, cardiovascular disease remains a leading cause of death worldwide. Identifying new targets is crucial for enhancing preventive and therapeutic strategies. The gut microbiome has been associated with coronary artery disease (CAD), however our understanding of specific changes during CAD development remains limited. We aimed to investigate microbiome changes in participants without clinically manifest CAD with different cardiovascular risk levels and in patients with ST-elevation myocardial infarction (STEMI). Methods and results In this cross-sectional study, we characterized the gut microbiome using metagenomics of 411 faecal samples from individuals with low (n = 130), intermediate (n = 130), and high (n = 125) cardiovascular risk based on the Framingham score, and STEMI patients (n = 26). We analysed diversity, and differential abundance of species and functional pathways while accounting for confounders including medication and technical covariates. Collinsella stercoris, Flavonifractor plautii, and Ruthenibacterium lactatiformans showed increased abundances with cardiovascular risk, while Streptococcus thermophilus was negatively associated. Differential abundance analysis revealed eight species and 49 predicted metabolic pathways that were differently abundant among the groups. In the gut microbiome of STEMI patients, there was a depletion of pathways linked to vitamin, lipid, and amino acid biosynthesis. Conclusion We identified four microbial species showing a gradual trend in abundance from low-risk individuals to those with STEMI, and observed differential abundant species and pathways in STEMI patients compared to those without clinically manifest CAD. Further investigation is warranted to gain deeper understanding of their precise role in CAD progression and potential implications, with the ultimate goal of identifying novel therapeutic targets.

Dystonia is a movement disorder in which patients have involuntary abnormal movements or postures. Non-motor symptoms, such as psychiatric symptoms, sleep problems and fatigue, are common. We hypothesise that the gut microbiome might play a role in the pathophysiology of the (non-)motor symptoms in dystonia via the gut–brain axis. This exploratory study investigates the composition of the gut microbiome in dystonia patients compared to healthy controls. Furthermore, the abundance of neuro-active metabolic pathways, which might be implicated in the (non-)motor symptoms, was investigated. We performed both metagenomic and 16S rRNA sequencing on the stool samples of three subtypes of dystonia (27 cervical dystonia, 20 dopa-responsive dystonia and 24 myoclonus-dystonia patients) and 25 controls. While microbiome alpha and beta diversity was not different between dystonia patients and controls, dystonia patients had higher abundances of Ruminococcus torques and Dorea formicigenerans, and a lower abundance of Butyrivibrio crossotus compared to controls. For those with dystonia, non-motor symptoms and the levels of neurotransmitters in plasma explained the variance in the gut microbiome composition. Several neuro-active metabolic pathways, especially tryptophan degradation, were less abundant in the dystonia patients compared to controls. This suggest that the gut–brain axis might be involved in the pathophysiology of dystonia. Further studies are necessary to confirm our preliminary findings.