Multi-omics study reveals that statin therapy is associated with restoration of gut microbiota homeostasis and improvement in outcomes in patients with acute coronary syndrome

Abstract

Rationale: Prior chronic treatment with statins has been shown to be associated with more favorable outcomes in patients with acute coronary syndrome (ACS). Specific changes in the gut microbiota and microbial metabolites have been shown to influence the progression of coronary artery disease. However, the critical microbial and metabolomic changes associated with the cardiovascular protective effects of statins in ACS remain elusive. Methods: In the present study, we performed 16S rRNA sequencing and serum metabolomic analysis in 36 ACS patients who had received chronic statin treatment, 67 ACS patients who had not, and 30 healthy volunteers. A follow-up study was conducted. Metagenomic functional prediction of important bacterial taxa was achieved using PICRUSt2. Results : Statins modulated the gut microbiome of ACS patients towards a healthier status, i.e., reducing potentially pathogenic bacteria such as Parabacteroides merdae but increasing beneficial bacteria such as Bifidobacterium longum subsp. longum , Anaerostipes hadrus and Ruminococcus obeum . Moreover, prior chronic statin therapy was associated with improved outcome in ACS patients. Multi-omics analysis revealed that specific changes in bacterial taxa were associated with disease severity or outcomes either directly or by mediating metabolites such as fatty acids and prenol lipids. Finally, we discovered that important taxa associated with statins were correlated with fatty acid- and isoprenoid-related pathways that were predicted by PICRUSt2. Conclusions: Our study suggests that statin treatment might benefit ACS patients by modulating the composition and function of the gut microbiome, which might result in improved circulating metabolites and reduced metabolic risk. Our findings provide new insights for understanding the heterogenic roles of statins in ACS patients through host gut microbiota metabolic interactions.

The Intestinal Effect of Atorvastatin: Akkermansia muciniphila and Barrier Function

“…Studies from animal or human cohorts have found that using statins profoundly alters the gut microbiota profile. Though the featured microbiota changes induced by statins are yet to be characterized, most studies linked the altered gut microbiota composition to positive therapeutic responses of statins on CAD outcomes (Khan et al, 2018;Kim et al, 2019;Dias et al, 2020;Kummen et al, 2020;Vieira-Silva et al, 2020;Hu et al, 2021). A recent report, however, revealed the negative side of statin-induced microbiota changes, which reduced fecal butyrate and increased secondary bile acid production in a PXR-dependent manner (Caparros-Martin et al, 2017).…”

Bifico Relieves Irritable Bowel Syndrome By Regulating Gut Microbiota Dysbiosis and Inflammatory Cytokines in an Animal Model

“…In the genera level, Parabacteroides and Sutterella were increased in the IBS group compared to the control group and the IBS + Bi co group. Parabacteroides and Parabacteroides merdae (belongs to Parabacteroides genera) were considered as potentially pathogenic bacterium that were reported to be frequently enriched in the hypertensive gut microbiome [45,46]. Moreover, in infectious diseases, Parabacteroides merdae is generally considered an opportunistic pathogen, which is able to develop antimicrobial drug resistance [47].…”

Alterations of Gut Microbiome and Serum Metabolome in Coronary Artery Disease Patients Complicated With Non-alcoholic Fatty Liver Disease Are Associated With Adverse Cardiovascular Outcomes

“…Bacterial DNA was isolated from fecal samples by using the bead-beating method. The DNA extracted from each sample was used as the template to amplify the V3-V4 region of 16S rRNA gene by using PCR (Phusion High-Fidelity PCR Master Mix with GC Buffer, from New England Biolabs Company), which were illustrated in our previous publication ( 24 ). Raw data quality control was performed.…”

“…The purified products were mixed at an equal ratio for sequencing using an Illumina MiSeq system (Illumina Inc., USA). The detailed method refers to our previous study ( 24 ).…”