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Gut Microbiome Composition Varies in Atherosclerotic Cardiovascular Disease

NEW YORK (GenomeWeb) – The gut microbiomes of people with atherosclerotic cardiovascular disease differ greatly from those of healthy people, according to a new study.

Previous work has suggested that the gut microbiome may influence the development of atherosclerosis. Microbes in the gut metabolize choline, phosphatidylcholine, and L-carnitine to produce trimethylamine (TMA), which is transformed in the liver into trimethylamine-N-oxide (TMAO), a major cause of atherosclerosis.

A BGI-Shenzhen-led team of researchers conducted a metagenome-wide association study using stool samples from some 200 people with atherosclerotic cardiovascular disease (ASCVD) and healthy controls. As they reported in Nature Communications yesterday, the researchers found that people with atherosclerotic cardiovascular disease had increased numbers of bacteria like Enterobacteriaceae and Streptococcus in their stool and that they could distinguish people with disease from healthy people.

"It is surprising that high abundances of microbes [that] are usually present in the oral cavity… are found in ASCVD patients and most of them can serve as ASCVD markers," first author Zhuye Jie from BGI-Shenzhen said in a statement.

Jie and colleagues performed metagenomic shotgun sequencing of 405 fecal samples from 218 people with ASCVD and 187 healthy people. The participants with ASCVD had 50 percent or higher stenosis of one or more vessel. The researchers aligned the reads they generated to a reference gut microbiome database, mapping about 80 percent of the reads from each sample.

Multivariate analysis separated the samples from people with ASCVD and controls. The researchers noted differences in abundance of certain microbes between the groups, as ASCVD samples harbored lower levels of Bacteroides and Prevotella, but higher numbers of Streptococcus and Escherichia.

In particular, there was an increased abundance of Enterobacteriaceae like Escherichia coli, Klebsiella species, and Enterobacter aerogenes among the samples from people with ASCVD, as compared to control samples.

They also noticed higher levels of bacteria like Streptococcus species, Lactobacillus salivarius, Solobacterium moorei, and Atopobium parvulum among the ASCVD samples. These bacteria are typically found in oral microbiome samples.

At the same time, microbes like Bacteroides species, Prevotella copri, and Alistipes shahii were less abundant in samples from people with ASCVD, as compared to controls, as were Roseburia intestinalis and Faecalibacterium cf. prausnitzii.

Jie and colleagues used these differences in gut microbiome makeup to develop a random forest classifier to distinguish people with ASCVD from controls. In all, they included 47 metagenomic linkage groups in the classifier and found that it could distinguish the two with an area under the curve of 86 percent.

The researchers also found that these metagenomic linkage groups were associated with certain clinical features. One such group, K. oxytoca correlated with serum levels of aspartate transaminase — a heart attack marker — α-hydroxybutyrate dehydrogenase, and creatine kinase. Others, meanwhile, were associated with diastolic blood pressure or systolic blood pressure.

By also comparing differences in functional pathways present in the microbiota of people with ASCVD and controls, the researchers found that people with ASCVD had a greater potential for the transport of simple sugars and amino acids, but a decreased potential for the biosynthesis of vitamins.

A number of the functional alterations were consistent with changes in the prevalence of bacteria that typically encode them. For instance, ACVD sample were enriched for genes involved in the synthesis of the O-antigen of lipopolysaccharides, which correlates with the enrichment of Enterobacteriaceae.

Jie and colleagues also found that some of these gut microbe changes also occurred in ASCVD-associated diseases like liver cirrhosis, type 2 diabetes, obesity, and rheumatoid arthritis. All of these conditions had increased levels of oral microbes within stool samples, though they noted that the gut microbiomes of each also had unique features.

"These findings may help explain the similarities and differences between [cardiometabolic diseases]," Jie added.