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October 10, 2017, Researchers from BGI-research, China National GeneBank in collaboration with the Kunlun He group from Chinese PLA General Hospital and the Shilong Zhong group fromGuangdong General Hospital, published their findings of gut microbiome in atherosclerotic cardiovascular disease (ASCVD) on Nature Communication. This is the first report on Chinese ASCVD patients with the largest sample up to now in the microbiome study of cardiovascular diseases. This study uncovered pronounced differences in the gut microbiota structure between ASCVD patients and healthy controls. This is also the first time that a group of patients with multiple comorbidities (liver cirrhosis, obesity, type 2 diabetes and rheumatoid arthritis) have been surveyed by metagenomics, and through mapping against a comprehensive high-quality reference gene catalog that includes both cultivated and uncultivated microbes, their microbiota are parsed on both taxonomic and functional levels.
Cardiovascular and metabolic diseases, collectively referred to as cardiometabolic diseases (CMDs), are associated with high morbidity and mortality, and impose increasingly heavy healthcare and economic burdens. Previous studies have shown that the gut microbiota metabolizes choline, phosphatidylcholine and L-carnitine to produce trimethylamine (TMA), which is oxidized in the liver into the proatherogenic metabolite, trimethylamine-N-oxide (TMAO). TMAO is one of the most potential casual factor for atherosclerosis, and inhibition of gut microbiota-dependent TMAO production has been shown as a promising strategy for the treatment of atherosclerosis. However, there may exist other mechanisms by which the gut microbiota is involved in the pathogenesis of CMD, but their discovery is impeded by the lack of a large CMD cohort for the extensive characterization of CMD patients’ microbiota.
To fill this gap, the researchers sequenced the microbial DNA from stool samples, representative of the gut microbiome, from 218 individuals with ASCVD and 187 healthy controls, and performed a metagenome-wide association study (MWAS). They identified multiple strains (metagenomic linkage groups, MLGs) and functional modules associated with ASCVD. At the validation stage, additional 845 samples from a published cohort were utilized to verify the ASCVD-associated microbial features found in this study.
Results showed that there were tremendous deviations in the gut microbiome of ASCVD patients from healthy control. Compare to healthy individuals, ASCVD patients were enriched in Enterobacteriaceae, which is often present in the oral cavity such as Streptococcus species of this clade, Lactobacillus salivarius, Solobacterium moorei, and Atopobium parvulum,and Clostridium clusters. In comparison, healthy controls were enriched in potentially beneficial microbial members such as F. prausnitzii. Further association studies with clinical index revealed that Streptococcus was positive correlated with blood pressure, and that Enterobacteriaceae was positively correlated with heart index. The risk predict model built on 47 microbes biomarkers showed good classification performance at a AUC of 86%.
“This is the first time that a gut microbiome study has been performed on a sizable number of CMD patients of Asian origin”, the first author Zhuye Jie says, “It is surprising that high abundances of microbes are usually present in the oral cavity, which are found in ASCVD patients and most of them can serve as ASCVD markers. ASCVD is commonlyaccompanied by other diseasessuch as type 2 diabetes, obesity, liver cirrhosis, and rheumatoid arthritis, which we altogether term CMDs, so it will be very interesting to investigate the differences and relationships between them. We found that CMDs share a lot of gut microbial markers, such as Streptococcus, and similar functional patterns such as the enhancement of PTS system and amino acid transporter system. Meanwhile, the distinct microbial features of each disease allow us to distinguish between CMDs based on the gut microbiota. These findings may help explain the similarities and differences between CMDs.”
The results of this study will inspire further studies on the gut microbiota and ASCVD, and provide potential microbial biomarkers for the noninvasive diagnosis of ASCVD and targets for the treatment of this disease.