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猪蹄鸡爪啃多了会emo？Cell子刊：食物中常见的这种氨基酸，竟与抑郁严重程度有关！

2022-07-21 四五七 MedSci原创

抑郁肠道菌群脯氨酸
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Cell Metabolism：脯氨酸与抑郁症严重程度相关，饮食和人体血浆中脯氨酸浓度越高，抑郁症状越严重，并且这一过程中，肠道菌群扮演了重要角色，后续的小鼠和果蝇实验也均证明了脯氨酸能够加剧抑郁

美食已然成为了当代年轻人的精神慰藉，心情不好，吃顿好的；工作累了，吃顿好的；放假休息，吃顿好的。
火锅、串串、炸鸡、奶茶…通通“炫“我嘴里，只有肚子饱了，心灵才不会空虚。
不过，不是所有食物都能改善心情，emo的时候啃猪蹄，搞不好还会加重抑郁情绪！
最近，来自西班牙的科学家就发现一种食物中常见氨基酸——脯氨酸，与抑郁症严重程度相关，饮食和人体血浆中脯氨酸浓度越高，抑郁症状越严重，并且这一过程中，肠道菌群扮演了重要角色，后续的小鼠和果蝇实验也均证明了脯氨酸能够加剧抑郁，emo翻倍的作用。该研究发表于Cell Metabolism。
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首先，为了调查饮食与抑郁症的关联，研究人员以问卷形式收集了116名参与者，其中包括44名非抑郁患者，47名轻度抑郁患者，25名重度抑郁患者的日常饮食情况。
按照问卷中93种常见食物及饮料的食用频率和营养成分配料表，研究人员就能大致分析每种营养素如：维生素、矿物质、氨基酸、脂肪酸等的摄入与抑郁程度是否存在关系。（注：本研究中通过PHQ-9抑郁症筛查量表评估参与者抑郁程度，得分越高抑郁程度越高）
结果显示，在所有的营养素中，脯氨酸对抑郁症影响最大。
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脯氨酸（Proline）作为一种非必需氨基酸，分布于多种蛋白质中，是胶原蛋白和软骨的重要构成成分，富含脯氨酸的食物有：猪蹄、软骨、鸡皮、鱼皮、牛蹄筋类和猪皮等。
但是，研究人员也发现，并不是所有吃猪蹄、摄入高脯氨酸饮食的人抑郁评分都高，这其中还离不开肠道菌群的作用，别忘了肠道菌群共享了我们吃下去的每一口食物。
有些人的肠道菌群刚好能够促进脯氨酸代谢，即使他吃下了高脯氨酸的食物，但是他血浆中的脯氨酸水平依然很低，因此抑郁评分就低；而那些肠道菌群不适应脯氨酸代谢，又吃了高脯氨酸食物的人，血浆中的脯氨酸水平高，抑郁评分也相应就高。
对参与者们的粪便进行分析，血浆脯氨酸水平高的参与者，肠道菌群中副拟杆菌属及酸氨基球菌属含量多，而双歧杆菌属及一些产生短链脂肪酸的菌属含量少，而血浆脯氨酸水平低的参与者肠道中则有更多促进脯氨酸转运和代谢的细菌。
 
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接下来，为了进一步证明脯氨酸确实能够影响抑郁严重程度，研究人员还在小鼠和果蝇身上进行了实验。
向小鼠饮食中添加脯氨酸，然后进行为期6周的不可预测慢性轻度压力刺激（unpredictable chronic mild stress），比如把小鼠放到一个45度倾斜的笼子、把小鼠的被窝弄湿、把小鼠放到一个拥挤的笼子里、让小鼠的被窝沾上陌生小鼠的味道、拿走小鼠的被窝并往笼子里注水……（小鼠：我麻了）。
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总之，6周过后，和普通饮食的小鼠相比，饮食中添加了脯氨酸的小鼠，抑郁症状更严重，具体表现为：提溜起小鼠的尾巴，小鼠悬空一动不动的时间更长了（绝望表现），对甜食的欲望也减退了（欣快感消失），说明饮食中添加脯氨酸确实能够让本就抑郁的小鼠，心情更加雪上加霜。
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血浆中脯氨酸水平高不高，除了受饮食影响，还要看肠道菌群的作用，于是，研究人员又将不同的抑郁程度的20名患者的粪便菌群移植到20只抗生素处理的小鼠身上，小鼠就获得了不同脯氨酸代谢能力的肠道菌群。
供者抑郁程度越高（也可以理解为肠道菌群脯氨酸代谢能力越差），接受粪菌移植的受体小鼠在后续的条件性恐惧实验中“僵硬”（freezing）时间就越长，说明来自抑郁患者的粪便菌群同样能够诱导小鼠出现情绪障碍。
重度抑郁障碍患者一个典型表现就是额叶功能下降，主要是涉及调控情绪、认知、决策功能的内侧前额叶皮层（mPFC）。
在移植了抑郁患者的粪便菌群后，研究人员还发现小鼠mPFC部位的脯氨酸转运蛋白Slc6a20表达发生改变，供者抑郁评分越高，受体小鼠mPFC的Slc6a20表达就越高。
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为了探明Slc6a20在抑郁中的作用，在果蝇实验中，研究人员敲低了果蝇神经细胞中Slc6a20基因表达，结果显示，敲低了Slc6a20基因表达果蝇即使在压力刺激的情况下，也不再表现出明显的抑郁行为。
以上实验提示mPFC中的脯氨酸转运蛋白参与调控抑郁行为的发生，而粪便菌群通过影响大脑脯氨酸转运蛋白的表达，进而影响抑郁严重程度。
最后，研究人员还向无菌果蝇中分别移植了两种肠道菌群，一种是有利于脯氨酸代谢的植物乳杆菌，一种是不利于脯氨酸代谢的阴沟肠杆菌，在压力刺激的情况下，移植了植物乳杆菌的果蝇抑郁表现更少，说明移植促脯氨酸代谢的肠道菌群具有抗抑郁效果。
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本研究首次揭示了脯氨酸、肠道菌群与抑郁症存在关系。
作为一个日益严重的公共卫生问题，全球超过3.5亿人饱受抑郁症的困扰，而抑郁症发生的潜在机制至今仍未阐明，目前抑郁症治疗的有效率约为60%-80%，复发率＞50%。降低膳食中脯氨酸水平，调节肠道菌群，或能为抑郁治疗提供新的方向。
参考文献：
[1]Mayneris-Perxachs J, Castells-Nobau A, Arnoriaga-Rodríguez M, et al. Microbiota alterations in proline metabolism impact depression. Cell Metab. 2022;34(5):681-701.e10. doi:10.1016/j.cmet.2022.04.001

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    2023-04-16 维他命

    #CEL#

    0

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    2022-09-25 zhaozhouchifen

    #Cell#

    0

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    2023-01-18 zhaohui6731

    #氨基酸#

    0

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    2022-11-10 szx39

    脯氨酸与肠道菌群，新亮点

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=1962799, encodeId=5f311962e9989, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Apr 16 00:25:56 CST 2023, time=2023-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872470, encodeId=699a18e2470c5, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Sep 25 18:25:56 CST 2022, time=2022-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1860894, encodeId=d3031860894cb, content=<a href='/topic/show?id=5e746403ed5' target=_blank style='color:#2F92EE;'>#氨基酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64037, encryptionId=5e746403ed5, topicName=氨基酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf3d82, createdName=zhaohui6731, createdTime=Wed Jan 18 10:25:56 CST 2023, time=2023-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2099569, encodeId=acd02099569cc, content=脯氨酸与肠道菌群，新亮点, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b2831614439, createdName=szx39, createdTime=Thu Nov 10 10:49:46 CST 2022, time=2022-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234016, encodeId=3c2b1234016b7, content=有意思！, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=969d2873055, createdName=走，走走, createdTime=Fri Jul 22 14:05:39 CST 2022, time=2022-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1416937, encodeId=8be3141693e4b, content=<a href='/topic/show?id=27c710101804' target=_blank style='color:#2F92EE;'>#食物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101018, encryptionId=27c710101804, topicName=食物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e3a33221853, createdName=yhy100201, createdTime=Fri Jul 22 10:25:56 CST 2022, time=2022-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555350, encodeId=3afb1555350f9, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Fri Jul 22 10:25:56 CST 2022, time=2022-07-22, status=1, ipAttribution=)]
    2022-07-22 走，走走

    有意思！

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1962799, encodeId=5f311962e9989, content=<a href='/topic/show?id=dbe6445416' target=_blank style='color:#2F92EE;'>#CEL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=74, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4454, encryptionId=dbe6445416, topicName=CEL)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c3ff68, createdName=维他命, createdTime=Sun Apr 16 00:25:56 CST 2023, time=2023-04-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1872470, encodeId=699a18e2470c5, content=<a href='/topic/show?id=fd764459a8' target=_blank style='color:#2F92EE;'>#Cell#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4459, encryptionId=fd764459a8, topicName=Cell)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=524d95, createdName=zhaozhouchifen, createdTime=Sun Sep 25 18:25:56 CST 2022, time=2022-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1860894, encodeId=d3031860894cb, content=<a href='/topic/show?id=5e746403ed5' target=_blank style='color:#2F92EE;'>#氨基酸#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=64037, encryptionId=5e746403ed5, topicName=氨基酸)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf3d82, createdName=zhaohui6731, createdTime=Wed Jan 18 10:25:56 CST 2023, time=2023-01-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2099569, encodeId=acd02099569cc, content=脯氨酸与肠道菌群，新亮点, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b2831614439, createdName=szx39, createdTime=Thu Nov 10 10:49:46 CST 2022, time=2022-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1234016, encodeId=3c2b1234016b7, content=有意思！, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=969d2873055, createdName=走，走走, createdTime=Fri Jul 22 14:05:39 CST 2022, time=2022-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1416937, encodeId=8be3141693e4b, content=<a href='/topic/show?id=27c710101804' target=_blank style='color:#2F92EE;'>#食物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101018, encryptionId=27c710101804, topicName=食物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=e3a33221853, createdName=yhy100201, createdTime=Fri Jul 22 10:25:56 CST 2022, time=2022-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1555350, encodeId=3afb1555350f9, content=<a href='/topic/show?id=f367681e434' target=_blank style='color:#2F92EE;'>#猪#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=68174, encryptionId=f367681e434, topicName=猪)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=9ec214601917, createdName=muzishouyi, createdTime=Fri Jul 22 10:25:56 CST 2022, time=2022-07-22, status=1, ipAttribution=)]
    2022-07-22 yhy100201

    #食物#

    0

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    2022-07-22 muzishouyi

    #猪#

    0

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