Nature Microbiology:吃红肉易导致心脏病?研究揭开红肉增加心血管疾病风险的具体机制

2021-12-29 “生物世界”公众号 “生物世界”公众号

之前已有许多研究发现,食用红肉与心脏病和死亡风险增加有关,还有研究显示,食用红肉与癌症风险增加有关。世界卫生组织癌症研究署于2017年将红肉列入2A级致癌物清单(该等级指很可能对人类致癌)。

隆冬之际,天寒地冻,约上三五好友,喝点小酒,吃个火锅,涮点牛羊肉,可谓人生一大乐事。然而,你是否知道,当你大口吃肉的同时,心脑血管疾病也在悄悄向你靠近?

之前已有许多研究发现,食用红肉与心脏病和死亡风险增加有关,还有研究显示,食用红肉与癌症风险增加有关。世界卫生组织癌症研究署于2017年将红肉列入2A级致癌物清单(该等级指很可能对人类致癌)。

红肉,是营养学名词,指在烹饪前呈现岀红色的肉,如猪肉、牛肉、羊肉、鹿肉、兔肉等等所有哺乳动物的肉都是红肉。

2021年12月23日,美国克利夫兰医学中心的研究人员在 Nature 子刊 Nature Microbiology 上发表了题为:The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism的研究论文。这项研究揭示了富含红肉的饮食如何增加心血管疾病风险的。

这些发现建立在主要通讯作者 Stanley Hazen 教授十多年的研究基础上。在之前一系列具有里程碑意义的研究中,Hazen教授发现,当肠道微生物消化富含肉碱的食物(如红肉和其他动物产品)时,会产生一种被称为氧化三甲胺(TMAO)的副产物,它会增加患心脏病和中风的风险。

如今,这项最新发现为肠道微生物在摄入富含红肉的饮食后将肉碱转化为促动脉粥样硬化和血液凝块的两步过程提供了更全面的理解。

Stanley Hazen教授表示,这些新研究确定了肠道微生物基因簇,该基因簇与第二步有关,该步骤将富含红肉的饮食与心脏病风险升高联系起来。这一发现将帮助我们找到新的治疗目标,以预防或减少与饮食有关的心血管疾病风险。

Stanley Hazen教授

2018年,Stanley Hazen教授及其团队在 Journal of Clinical Investigation 期刊发表的一项研究结果显示,膳食肉碱在肠道中通过两个肠道微生物参与的步骤转化为氧化三甲胺(TMAO)。这一过程中的中间代谢物是一种叫做γBB(γ-丁基甜菜碱)的分子。

Stanley Hazen教授表示,多种肠道微生物可以将膳食中的肉碱转化为γBB,但很少有微生物能将分子转化为TMA(TMAO的前体)。在杂食动物中,肠道细菌 E. timonensis 是参与γBB转化为TMA/TMAO的主要人类肠道微生物。相反,长期素食者和纯素食者的肠道中这种微生物的含量非常低,因此几乎没有能力将肉碱转化为TMAO。

研究团队利用从近3000名患者收集的样本和临床数据,研究了空腹血浆γBB水平与疾病结局之间的关系。较高的γBB水平与心血管疾病和主要不良事件(包括死亡、非致命性心脏病发作或中风)有关。

γBB水平的升高与人类受试者心血管疾病风险的增加有关

为了理解γBB和观察到的患者结果之间的机制联系,研究人员研究了从小鼠和患者收集的粪便样本,以及动脉损伤的临床前模型。他们发现,引入的肠道细菌 E. timonensis 完成了肉碱向TMAO的转化,提高了TMAO水平,增加了凝血风险。

肠道微生物将肉碱转化为γBB,再转化为TMAO

紧接着,研究人员使用测序技术来识别相关的肠道微生物基因簇。根据新发现的功能,该基因簇被命名为gbu基因簇,共有6个基因。他们发现,在γBB存在的情况下,gbu基因簇中所有6个基因的表达都增加,其中4个基因(gbuA、gbuB、gbuC和gbuE)在γBB向TMA/TMAO的转化中至关重要。

E. timonensis的gbu基因簇对γBB向TMA/TMAO的转化至关重要

通过研究患者样本,研究团队发现gbuA的丰度与富含红肉的饮食和血浆TMAO水平显着相关,而素食者的肠道微生物gbuA水平较低。这表明调整饮食可能有助于降低与饮食和TMAO相关的心血管疾病风险。

研究模式图

综上所述,这项研究发现,当我们摄入红肉等富含肉碱的食物时,多种肠道微生物可以将膳食中的肉碱转化为γBB,随后一种特殊的肠道细菌 E. timonensis 会增加gbu基因簇的表达,并将γBB转化为氧化三甲胺(TMAO),从而增加了心血管疾病的风险。

基于这一原理,gbu基因簇的作用十分值得我们进一步探索,未来也许能作为一个潜在的、预防和治疗心血管疾病的靶点。

原始出处:

Buffa, J.A., Romano, K.A., Copeland, M.F. et al. The microbial gbu gene cluster links cardiovascular disease risk associated with red meat consumption to microbiota L-carnitine catabolism. Nat Microbiol (2021). https://doi.org/10.1038/s41564-021-01010-x.

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    2022-06-26 xjy02
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    2022-06-19 sunylz
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    2022-02-25 liye789132251
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