專題討論14:腸道菌落與動脈硬化
Gut Microbiota and Atherosclerosis

程 序 表

S14-6
Targeting the gut microbiome as a treatment for cardiovascular diseases
陳明汝
國立臺灣大學

  Recently, both human and animal experiments have revealed that gut microflora dysbiosis can accelerate the progression of cardiovascular diseases (CVDs) due to inducing a chronic inflammatory state by endotoxaemia and upregulating gut permeability. Additionally, several dietary-related effects of the gut microbiota contribute to the pathogenesis of CVD, such as trimethylamine N-oxide (TMAO), short chain fatty acids (SCFA), secondary bile acid and indoxyl sulfate (IS), affecting the host physiological processes by activation of numerous signaling pathways. Thus, understanding the gut microbiome is crucial not only because the gut microbiome–drug interaction plays a role in drug bioavailability, activity and toxicity, the intestinal microbiome also provides a new potential therapeutic target for the treatment of CADs.
  Intervention studies in humans directing to selectively modify the composition of the microbiota or to pharmacologically manipulate the microbiota to influence production of their metabolites are investigated. Consumption of specific strains of probiotics showed anti-atherogenic effects involving in increase of the bacterial diversity in gut with changes in colon levels of SCFA and decrease in levels of proinflammatory cytokines. Selection of health promoting foods, such as fibers and polyphenols, could be converted into biologically active compounds by the colonic microorganisms, so also upregulating the colon-systemic metabolic axis. Besides, interventions, that target leaky mucosal membranes, endotoxin-coupled lipid absorption or removal of circulating endotoxins, demonstrate a potential to reduce the progression of inflammatory-induced metabolic diseases. For example, in both animals and humans, oral administration of bovine colostrum-derived anti-LPS compounds were associated with the alleviation of insulin resistance, hyperlipidemia and liver damage associated with the metabolic syndrome. Furthermore, both Bariatric surgery and physical activity also alter gut microbiome. Bariatric procedures such as the Roux-en-Y gastric bypass (RYGB) operation improve obesity-associated metabolic disorders in addition to their weight loss effects. These surgically induced metabolic shifts were related to an alteration of the gut microbiota. Exercise increases fecal concentrations of SCFA leading to enhance energy within a physically active subjects, thereby becoming a survival benefit during caloric deficient periods.
  In summary, the human microbiome has been intensively studied as a therapeutic target using various approaches. In the future, a positive shift towards and inclusive view of precision medicine is anticipated that encompasses both human and microbial genomes as well as their combined metabolic activities.