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

Abstract

Rationale: Patients suffering from coronary artery disease (CAD) complicated with nonalcoholic fatty liver disease (NAFLD) present worse cardiovascular outcomes than CAD patients without NAFLD. The progression of CAD is recently reported to be associated with gut microbiota and microbe-derived metabolites. However, it remains unclear how the complication of NAFLD will affect gut microbiota and microbe-derived metabolites in CAD patients, and whether or not this interplay is related to the worse cardiovascular outcomes in CAD-NAFLD patients.Methods: We performed 16S rRNA sequencing and serum metabolomic analysis in 27 CAD patients with NAFLD, 81 CAD patients without NAFLD, and 24 matched healthy volunteers. Predicted functional profiling was achieved using PICRUSt2. The occurrence of cardiovascular events was assessed by a follow-up study. The association of alterations in the gut microbiome and metabolome with adverse cardiovascular events and clinical indicators was revealed by Spearman correlation analysis.Results: We discovered that the complication of NAFLD was associated with worse clinical outcomes in CAD patients and critical serum metabolome shifts. We identified 25 metabolite modules that were correlated with poor clinical outcome in CAD-NAFLD patients compared with non-NAFLD patients, represented by increased cardiac-toxic metabolites including prochloraz, brofaromine, aristolochic acid, triethanolamine, and reduced potentially beneficial metabolites including estradiol, chitotriose, palmitelaidic acid, and moxisylyte. In addition, the gut microbiome of individuals with CAD-NAFLD was changed and characterized by increased abundances of Oscillibacter ruminantium and Dialister invisus, and decreased abundances of Fusicatenibacter saccharivorans, Bacteroides ovatus and Prevotella copri. PICRUSt2 further confirmed an increase of potential pathogenic bacteria in CAD-NAFLD. Moreover, we found that variations of gut microbiota were critically correlated with changed circulating metabolites and clinical outcomes, which revealed that aberrant gut microbiota in CAD-NAFLD patients may sculpt a detrimental metabolome which results in adverse cardiovascular outcomes.Conclusions: Our findings suggest that CAD patients complicated with NAFLD result in worse clinical outcomes possibly by modulating the features of the gut microbiota and circulating metabolites. We introduce “liver-gut microbiota-heart axis” as a possible mechanism underlying this interrelationship. Our study provides new insights on the contribution of gut microbiota heterogeneity to CAD-NAFLD progression and suggests novel strategies for disease therapy.

Identification of oral bacteria in the gut, atherosclerotic plaque, and cultured blood samples of patients with cardiovascular diseases – A secondary analysis of metagenomic microbiome data

“…Moreover, studies have shown that the LPS of E. coli can penetrate cardiac tissues and reach blood circulation, which leads to a thrombogenic effect (Carnevale et al 2020). E. coli, along with Dialister invisus, has been linked with periodontal abscess, periodontitis, caries, halitosis, apical periodontitis-infected pulpal tissues, and decayed teeth (Tandon et al 2013;Hu et al 2022). This strengthens the relationship between these oral diseases and CVDs, which has been proven by various studies (Sanz et al 2020;Kim et al 2019).…”

Fibroblast Growth Factor 19 Alters Bile Acids to Induce Dysbiosis in Mice With Alcohol-Induced Liver Disease

“…Contrary to our results, P excrementihominis is reduced in patients with either alcohol-associated hepatitis 52 or cardiovascular disease complicated with nonalcoholic fatty liver disease, positioning this species as potentially protective. 53 However, another recent study demonstrated P excrementihominis was induced significantly in patients with irritable bowel syndrome and may be associated with intestinal inflammation. 21 Our data indicate significantly increased inflammatory gene expression in liver, ileum, and colon, which could be mediated by changes in the gut microbiome and increased circulating LPS ( Figure 6 A ).…”

Effects of dietary supplementation of fish oil plus vitamin D3 on gut microbiota and fecal metabolites, and their correlation with nonalcoholic fatty liver disease risk factors: a randomized controlled trial

“…Additionally, a study of 132 participants showed that the gut microbiome of individuals with coronary artery disease coexisting with NAFLD was characterized by increased abundance of Dialister compared with healthy volunteers. 38 Interestingly, a case-control study of Chinese urban adults showed that the relative abundance of Dialister was higher in NAFLD subjects compared with healthy participants, and it was higher in males compared with female NAFLD subjects. 39 The above-mentioned results have demonstrated that fish oil plus vitamin D 3 has respectable efficacy in the treatment of NAFLD by regulating the gut microbiota.…”