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Cardiovascular disease (CVD) is a serious threat to human health, killing more than 17 million people worldwide each year
.
Atherosclerosis (AS) is the basis of pathological changes in cardiovascular diseases, its pathogenesis is complex, and there is a lack of targeted therapeutic drugs and means
.
Human gut microbiome studies have found that gut microbiota plays a key role in CVD, with multiple gut microbiome-derived metabolites showing anti- or AS-promoting effects
.
The team of Liu Hongwei/Liu Shuangjiang of the Institute of Microbiology found that a fungal active molecule could significantly improve the symptoms of atherosclerosis in mice, and further intestinal microbiota analysis found that after oral administration of this molecule, the abundance of Parabacteroid merdaede fecal core bacteria increased by 420 times
.
Analyzing a cohort of atherosclerosis from China and a cohort of CVD in a European population, the researchers found that the abundance of Paratypoides faeciocal in the intestinal region was significantly negatively correlated with
CVD disease.
ApoE-/- Atherosclerotic mice colonized with a strain of Paraesis fecal significantly reduced the symptoms of arteriosclerosis
.
Further targeted metabolomic analysis showed that the levels of fecal BCAAs in mice increased significantly after colonization with Parabacteroides faecals, and the levels of BCAAs in feces and blood decreased significantly
.
Elevated blood BCAA levels have been shown to be closely related
to the occurrence and development of insulin resistance, fatty liver and cardiovascular disease.
Genomic analysis and in vitro fermentation experiments confirmed that Parabacteroides faecalis has the ability to
degrade branched-chain amino acids into branched-chain short-chain fatty acids.
After the key gene porA knockout of the key gene porA for the breakdown of branched-chain amino acids of Parabacteroides faecal, the anti-atherosclerotic effect of the bacterium disappeared
.
Studies have confirmed that Parabacteroides fecal exerts anti-atherosclerosis by promoting the catabolism of intestinal branched-chain amino acids, reducing the concentration of branched-chain amino acids in the blood, improving insulin resistance, inhibiting the activation of the mTORC1 signaling pathway of arterial plaque macrophages
.
A long-term high-fat diet and a high-cholesterol diet can induce atherosclerosis
through different pathological mechanisms.
The study found that Paratypoides faecalices improved atherosclerosis with high fat-induced obesity with insulin resistance better than the atherosclerosis model
caused by a high cholesterol diet.
Further analysis of the CVD cohort showed that the blood BCAA amino acid level of CVD patients was significantly higher than that of healthy people, and the abundance of porA gene of intestinal flora was significantly lower than that of healthy control population
.
The study revealed the key role of intestinal microbial dysregulation, especially the abnormal metabolism of intestinal branched-chain amino acids in the occurrence and development of CVD diseases, proved the important potential of targeted regulation of intestinal microbiota microecology in the treatment of CVD diseases, and provided new ideas
for clinical treatment.
The results have been published online in the internationally authoritative journal Nature Metabolism, entitled "Gut Parabacteroides merdae protects against cardiovascular damage by enhancing.
" branched-chain amino acid catabolism”
。 Nature Metabolism published Herbert Tilg at the same time under the title "A gut bacterium tackles atherosclerosis.
" Professor's Monograph "News & Views"
.
Dr.
Shanshan Qiao of Hongwei's research group and researcher Liu Chang of Shandong University are the joint first authors of the paper, and researchers Liu Hongwei and Liu Shuangjiang of the Institute of Microbiology are the co-corresponding authors
.
This work was supported
by the National Key Research and Development Program and the Strategic Leading Science and Technology Special Project of the Chinese Academy of Sciences (Category B).
Figure 1 Parabacteroid merdaede improves atherosclerosis mechanisms
