吃红肉增加心血管疾病风险再添新证据,源于肠道菌群的代谢物

2022-08-03 甲遇庚 “生物世界”公众号

长期以来,科学家们已经将饱和脂肪、膳食胆固醇、钠、亚硝酸盐,甚至是高温烹饪等因素与ASCVD的风险增加联系了起来,认为大口吃肉这种不健康的饮食习惯是诱发ASCVD的重要因素之一。

动脉粥样硬化性心血管疾病(简称:ASCVD)是包括冠心病 、心肌梗死、中风等在内的一组心脏和血管疾病的总称。ASCVD已连续多年蝉联全球每年发病率和死亡率排行榜的榜首,仅2020年一年就夺走了近1860万人的生命,其中三分之一发生在70岁以下人群。

长期以来,科学家们已经将饱和脂肪、膳食胆固醇、钠、亚硝酸盐,甚至是高温烹饪等因素与ASCVD的风险增加联系了起来,认为大口吃肉这种不健康的饮食习惯是诱发ASCVD的重要因素之一。然而,到目前为止,还缺乏上述因素导致疾病机制的确凿证据。

2022年8月1日,美国心脏病协会杰出科学家、克利夫兰诊所心血管与代谢科学系主任 Stanley Hazen 教授和塔夫茨大学弗里德曼营养科学与政策学院 Dariush Mozaffarian 教授领导的研究团队在 Arteriosclerosis, Thrombosis, and Vascular Biology(ATVB)上发表了题为:Dietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study 的研究论文。

该团队首次研究了动物源性食物与动脉粥样硬化性心血管疾病(ASCVD)风险之间的相互关系、肠道菌群副产物和传统的ASCVD风险途径(如血液胆固醇、血压和血糖)对ASCVD风险的调节作用。同时,确定了有助于解释疾病风险的潜在生物途径。

Stanley Hazen教授

此前,对红肉摄入和健康的大部分关注都围绕着饮食中的饱和脂肪和血液胆固醇水平。这些新发现有助于回答长期以来关于肉类摄入量与心血管疾病风险之间的机制问题。

该研究第一作者、塔夫茨大学弗里德曼营养科学与政策学院博士后研究员 Meng Wang 表示,根据这项研究发现,新的干预措施可能有助于针对红肉和肠道微生物组之间的相互作用,以帮助我们找到降低心血管疾病风险的方法。

包括红肉(猪牛羊肉等)、加工肉类(熟食)、鱼、家禽和蛋品在内的动物源性食物是每日膳食的主要组成部分。这些不同的食物对动脉粥样硬化性心血管疾病(ASCVD)的影响已被广泛研究,但得到确切的证据仍然存在挑战。老年人是ASCVD风险最高的人群,充足的高质量蛋白质(动物源性食品)对于抵消与衰老相关的肌肉质量和力量损失似乎很重要。然而,科学家们对这些关联背后的潜在机制知之甚少。

该团队假设红肉和加工肉类的摄入量与ASCVD的发病率呈正相关,并且这些关联部分是由血浆中三甲胺氧化物(TMAO)相关代谢物水平介导的。

当摄入高脂食物之后,食物残渣进入肠道,被肠道细菌转化为三甲胺(TMA),TMA 进入肝脏后,被黄素单加氧酶(FMO)氧化为TMAO 。TMAO的作用是抑制血液中胆固醇的降解。因此,胆固醇就只能沉积到动脉血管壁,导致血管壁加厚、硬化。

Stanley Hazen 教授等人此前的研究已经证实血浆中高水平TMAO与动脉粥样硬化形成有关。

2022年5月22日,Dariush Mozaffarian 教授等人在 JAMA 子刊 JAMA Network Open 上发表的一项涉及5333名参与者的心血管心脏研究中发现,老年人的TMAO和相关代谢物水平与较高的死亡风险呈正相关。血浆中TMAO及其生物标志物水平最高的参与者死亡风险比水平最低的参与者高出20%至30% 。

在这项新研究中,该团队调查了一项始于1989年的美国心血管健康研究,参与者年龄均在65岁以上,63.5%为女性。研究人员在基线和随访期间测量了参与者几种血液生物标志物,包括TMAO及其两种关键的中间代谢物γ-丁基甜菜碱和巴豆甜菜碱的水平,它们来自红肉中丰富的肉碱。

TMAO及其中间代谢物的生成途径

在后续的随访中,参与者的病史、生活方式、健康状况和社会人口特征(如家庭收入、教育和年龄)都被收集和评估。他们还在研究开始时以及1995年至1996年期间回答了两份经过验证的食物频率问卷,以了解他们通常的饮食习惯,包括红肉、加工肉、鱼、家禽和鸡蛋的摄入量。

研究人员发现,在平均12.5年的随访中,未加工红肉、总肉类和总动物源性食物的摄入量与较高的ASCVD风险有关。

饮食、肠道菌群生成的 TMAO 相关代谢物和 ASCVD 的关系概念图

具体而言:

每天食用1.1份肉类(约90克)会增加22%的ASCVD发病风险,其中约10%的风险由摄入红肉后经肠道细菌产生的三种代谢物(TMAO、γ-丁基甜菜碱和巴豆甜菜碱)水平介导;

与肉类摄入相关的ASCVD较高风险部分由血糖和胰岛素水平介导;

对于加工肉类而言,ASCVD风险增加由系统性炎症介导,但与血压或血液胆固醇水平无关;

此外,在家禽、鸡蛋或鱼类中没有发现这一关联。

研究共同通讯作者、Dariush Mozaffarian 教授表示,该研究确定了有助于解释红肉和加工肉类与动脉粥样硬化心血管疾病之间联系的三个主要途径,即与肠道菌群相关的代谢物,如TMAO、血糖水平和系统性炎症,它们中的每一种似乎都比与血液胆固醇或血压相关的途径更重要。这意味着,在选择动物源性食物时,关注总脂肪、饱和脂肪或胆固醇的差异不是最重要的;而更好地了解食物中的其他成分(如肉碱和血红素铁)对健康的影响才是最重要的。

Stanley Hazen 教授表示,这项研究将肠道细菌-TMAO通路与动物源性食物和动脉粥样硬化性心血管疾病风险增加联系了起来。选择合理的饮食是降低这种风险的一种手段,因为饮食干预可以显着降低TMAO的水平。

原始出处:

Amanda M. Fretts, et al. Association of Trimethylamine N-Oxide and Metabolites With Mortality in Older Adults. JAMA Netw Open. 2022;5(5):e2213242. doi:10.1001/jamanetworkopen.2022.13242.

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  4. [GetPortalCommentsPageByObjectIdResponse(id=1660030, encodeId=f0d71660030bf, content=<a href='/topic/show?id=24e82545262' target=_blank style='color:#2F92EE;'>#代谢物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25452, encryptionId=24e82545262, topicName=代谢物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c1225086772, createdName=旅苦化文_216, createdTime=Sun Sep 18 16:09:30 CST 2022, time=2022-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1392495, encodeId=8237139249584, content=<a href='/topic/show?id=223081e33b6' target=_blank style='color:#2F92EE;'>#肠道菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81733, encryptionId=223081e33b6, topicName=肠道菌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aa292500107, createdName=1249897bm37(暂无昵称), createdTime=Fri Aug 05 03:09:30 CST 2022, time=2022-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1473343, encodeId=09da14e3343d3, content=<a href='/topic/show?id=862be0746bc' target=_blank style='color:#2F92EE;'>#疾病风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70746, encryptionId=862be0746bc, topicName=疾病风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3c757221906, createdName=花花1368, createdTime=Fri Aug 05 03:09:30 CST 2022, time=2022-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1499096, encodeId=6c891499096ac, content=<a href='/topic/show?id=bb6f89e145a' target=_blank style='color:#2F92EE;'>#血管疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89714, encryptionId=bb6f89e145a, topicName=血管疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ccb99370406, createdName=andy2090, createdTime=Fri Aug 05 03:09:30 CST 2022, time=2022-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1236644, encodeId=8a6a123664496, content=抛弃动物蛋白、脂肪的好处和必要性,就提心血管风险,他们吃饱了,就告诉咱有害, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJLxEbhSEziblP49HVwdGqT9ZA10TKycvqlJEWIPICGKMneOAVALCYkM6RFdibTuGa6XuvjHqNXOQcw/132, createdBy=20932540713, createdName=ColinGao, createdTime=Thu Aug 04 19:38:23 CST 2022, time=2022-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1236491, encodeId=5e2e12364918e, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=47401570839, createdName=waj970409, createdTime=Thu Aug 04 06:56:26 CST 2022, time=2022-08-04, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1660030, encodeId=f0d71660030bf, content=<a href='/topic/show?id=24e82545262' target=_blank style='color:#2F92EE;'>#代谢物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25452, encryptionId=24e82545262, topicName=代谢物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6c1225086772, createdName=旅苦化文_216, createdTime=Sun Sep 18 16:09:30 CST 2022, time=2022-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1392495, encodeId=8237139249584, content=<a href='/topic/show?id=223081e33b6' target=_blank style='color:#2F92EE;'>#肠道菌#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=81733, encryptionId=223081e33b6, topicName=肠道菌)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=aa292500107, createdName=1249897bm37(暂无昵称), createdTime=Fri Aug 05 03:09:30 CST 2022, time=2022-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1473343, encodeId=09da14e3343d3, content=<a href='/topic/show?id=862be0746bc' target=_blank style='color:#2F92EE;'>#疾病风险#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=29, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=70746, encryptionId=862be0746bc, topicName=疾病风险)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3c757221906, createdName=花花1368, createdTime=Fri Aug 05 03:09:30 CST 2022, time=2022-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1499096, encodeId=6c891499096ac, content=<a href='/topic/show?id=bb6f89e145a' target=_blank style='color:#2F92EE;'>#血管疾病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=89714, encryptionId=bb6f89e145a, topicName=血管疾病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=ccb99370406, createdName=andy2090, createdTime=Fri Aug 05 03:09:30 CST 2022, time=2022-08-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1236644, encodeId=8a6a123664496, content=抛弃动物蛋白、脂肪的好处和必要性,就提心血管风险,他们吃饱了,就告诉咱有害, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJLxEbhSEziblP49HVwdGqT9ZA10TKycvqlJEWIPICGKMneOAVALCYkM6RFdibTuGa6XuvjHqNXOQcw/132, createdBy=20932540713, createdName=ColinGao, createdTime=Thu Aug 04 19:38:23 CST 2022, time=2022-08-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1236491, encodeId=5e2e12364918e, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=47401570839, createdName=waj970409, createdTime=Thu Aug 04 06:56:26 CST 2022, time=2022-08-04, status=1, ipAttribution=)]
    2022-08-04 ColinGao

    抛弃动物蛋白、脂肪的好处和必要性,就提心血管风险,他们吃饱了,就告诉咱有害

    0

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    2022-08-04 waj970409

    学习

    0

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