| Cardiovascular diseases?CVDs?are the leading cause of death worldwide because of the complications of atherosclerosis.On the basis of WHO statistics,15.2 million people died of cardiovascular diseases such as ischemic heart disease and stroke,accounting for 26.7%of the total number of deaths worldwide in 2016.The current treatment of atherosclerosis is mainly to reduce serum high cholesterol,such as statin drugs in the prevention and treatment of the disease.However,this method only reduces cardiovascular mortality by 30%.There are still a large number of patients who are not sensitive to statins and other conventional therapies,and eventually die from myocardial infarction or stroke.Trimethylamine N-oxide?TMAO?,which is metabolized from diatery choline,phosphatidylcholine and carnitine by gut microbiota,can induce inflammation and promote atherosclerosis.TMAO has become one of the new targets for the prevention and treatment of atherosclerosis.Although it has been reported that some small molecule compounds are used to reduce serum TMAO levels,there are no reports on the use of probiotics to effectively inhibit TMAO production and prevent TMAO-induced atherosclerosis.Based on this,we screened probiotics from the feces of healthy people and screened probiotics that reduced serum TMAO levels and TMAO-induced atherosclerosis in animal models with high serum TMAO levels.The specific details are as follows:?1?Effect of Trimethylamine Degrading Bacteria on Serum level of TMAO in Mice In the present study,82 isolates were screened from healthy Chinese fecal samples on a basal salt medium supplemented with TMA as the sole carbon source.The isolates belonged to the family Enterobacteriaceae,particularly to genera Klebsiella,Escherichia,Cronobacter,and Enterobacter.Serum TMAO and cecal TMA levels were significantly decreased in choline-fed mice treated with Enterobacter aerogenes ZDY01 compared with those in choline-fed mice treated with phosphate-buffered saline.The proportions of Bacteroidales family S24-7 were significantly increased,whereas the proportions of Helicobacteraceae and Prevotellaceae were significantly decreased through the administration of E.aerogenes ZDY01.Results indicated that the use of probiotics to act directly on the TMA in the gut might be an alternative approach to reduce serum TMAO levels and to prevent the development of atherosclerosis and“fish odor syndrome”through the effect of TMA on the gut microbiota.?2?Effect of Lactobacillus plantarum on Serum level of TMAO in MiceAlthough E.aerogenes ZDY01 in the previous chapter can significantly reduce cecal TMA and serum TMAO levels,it is a conditional pathogen and is not suitable for clinical use.Therefore,we have administered five potential probiotics?Lactobacillus plantarum ZDY04,Lactobacillus rhamnosus ZDY9,Lactobacillus plantarum ZDY01,Lactobacillus casei ZDY8 and Lactobacillus bulgaricus ZDY5?to BALB/c mice fed with 1.3%choline.The results showed that only Lactobacillus plantarum ZDY04 can significantly reduce cecal TMA and serum TMAO levels via regulating the relative abundance of the family Lachnospiraceae,Erysipelotrichaceae,Bacteroidaceae and genus Mucispirillum,rather than reducing cecal TMA and serum TMAO levels by altering liver FMO3 expression levels and metabolizing intestinal choline,TMA,and TMAO.?3?Effect of Lactobacillus plantarum ZDY04 on TMAO-induced atherosclerosisIt has been previously shown that Lactobacillus plantarum ZDY04 reduces the level of serum TMAO in mice by altering the intestinal flora of mice.Therefore,to investigate the effect of Lactobacillus plantarum ZDY04 on TMAO-induced atherosclerosis and its mechanism,Lactobacillus plantarum ZDY04 was intragastrically administered to ApoE-/-mice fed with 1.3%choline for 16 weeks.The full-length aorta and heart of the mice were collected and detected by oil red O staining.Mouse atherosclerotic plaque area and the expression levels of related genes were detected.The results showed that Lactobacillus plantarum ZDY04 significantly reduced the plaque area of full-length aorta and aortic sinus in mice,and inhibited macrophage foaming,aortic inflammatory cytokines expression and cholesterol transport. |
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