Nat Metab:肠道微生物代谢产物甲酸盐可加剧结直肠癌的发生发展

2022-04-28 xiaozeng MedSci原创

肠道微生物代谢产物甲酸盐是结直肠癌发生发展相关的肠源性癌代谢物。

结直肠癌(CRC)作为全球最常见的癌症类型之一,其在癌症发病率上排名第三,在癌症相关死亡率上排名第二。既往研究显示,肠道微生物组与结直肠癌的发生、发展以及治疗中涉及的相关分子机制息息相关。


肠道微生物组是CRC发生发展期间免疫调节和肿瘤微环境产生的关键参与者。既往研究中发现,分离的肠道微生物会诱导遗传变异和微环境的改变,最终诱导肿瘤的生长。然而,肠道微生物组-宿主代谢稳态破坏的相关研究仍较少,目前继续更多的CRC微生物组研究。


既往的内外源实验及模型研究均揭示,具核梭杆菌(F. nucleatum,Fn)能够促进CRC的发生发展。在该研究中,研究人员旨在探究Fn在CRC发病中参与的代谢作用和相关的代谢稳态机制。


高梭杆菌丰度的CRC患者中甲酸盐生成相关基因pfl的表达显著增高

研究人员发现,甲酸盐是一种由CRC相关的Fn所产生的代谢物,其可促进CRC的发生发展。在该研究中,研究人员描述了CRC表型与梭杆菌丰度的相关性。共培养Fn和患者来源的CRC细胞显示出相应的促癌作用,同时伴随着甲酸盐代谢分泌的增加以及谷氨酰胺代谢的增强。


进一步研究显示,微生物组衍生的甲酸盐可通过介导AhR信号转导通路驱动CRC的侵袭,并增加肿瘤细胞的干细胞特性。小鼠模型研究发现,给予具核梭杆菌或甲酸盐能够引起肿瘤发生率或肿瘤大小的增加,同时伴随着Th17细胞的扩增,其可促进炎症反应。


相关分子示意图

 

总而言之,该研究鉴定甲酸盐为结直肠癌发生发展相关的肠源性癌代谢物。


原始出处:

Ternes, D., Tsenkova, M., Pozdeev, V.I. et al. The gut microbial metabolite formate exacerbates colorectal cancer progression. Nat Metab (18 April 2022).https://doi.org/10.1038/s42255-022-00558-0.

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    2023-03-20 liye789132251
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    2022-07-26 guojianrong
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encryptionId=71353e8964f, topicName=发生发展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Fri Sep 02 10:47:51 CST 2022, time=2022-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1897012, encodeId=411c189e012d5, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Wed Nov 16 11:47:51 CST 2022, time=2022-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798417, encodeId=df941e9841774, content=<a href='/topic/show?id=08276918eab' target=_blank style='color:#2F92EE;'>#生物代谢#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=69187, encryptionId=08276918eab, topicName=生物代谢)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/iaP1mV9qBwx5tE2F4xcG1r4x1PibWvluIFLB8VsViakqNMBia2Z0wFibVrYwDEILvHB1OomzzTAAGy5MVl5BrdEv9Bw/132, createdBy=e11f100, createdName=guguangxiang, createdTime=Fri Aug 26 13:47:51 CST 2022, time=2022-08-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1453701, encodeId=d1f71453e0167, content=<a href='/topic/show?id=098ee8679ad' target=_blank style='color:#2F92EE;'>#结直肠#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=78679, encryptionId=098ee8679ad, topicName=结直肠)], attachment=null, authenticateStatus=null, createdAvatar=/v1.0.0/img/user_icon.png, createdBy=9ace5575596, createdName=crystal0564, createdTime=Fri Apr 29 13:47:51 CST 2022, time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1513479, encodeId=79c915134e996, content=<a href='/topic/show?id=8e4b2540671' target=_blank style='color:#2F92EE;'>#代谢产物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25406, encryptionId=8e4b2540671, topicName=代谢产物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e1510553828, createdName=124987c6m39暂无昵称, createdTime=Fri Apr 29 13:47:51 CST 2022, time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1215424, encodeId=7860121542488, content=认真***, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Thu Apr 28 19:54:11 CST 2022, time=2022-04-28, status=1, ipAttribution=)]
    2022-09-02 wgsun
  5. [GetPortalCommentsPageByObjectIdResponse(id=1885754, encodeId=702f1885e5411, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Mar 20 00:47:51 CST 2023, time=2023-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1825387, encodeId=c66d182538e32, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, 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encryptionId=71353e8964f, topicName=发生发展)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=346311, createdName=wgsun, createdTime=Fri Sep 02 10:47:51 CST 2022, time=2022-09-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1897012, encodeId=411c189e012d5, content=<a href='/topic/show?id=4a391158248' target=_blank style='color:#2F92EE;'>#MET#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11582, encryptionId=4a391158248, topicName=MET)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=18fc139, createdName=一闲, createdTime=Wed Nov 16 11:47:51 CST 2022, time=2022-11-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1798417, encodeId=df941e9841774, content=<a href='/topic/show?id=08276918eab' target=_blank style='color:#2F92EE;'>#生物代谢#</a>, beContent=null, objectType=article, channel=null, level=null, 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time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1513479, encodeId=79c915134e996, content=<a href='/topic/show?id=8e4b2540671' target=_blank style='color:#2F92EE;'>#代谢产物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25406, encryptionId=8e4b2540671, topicName=代谢产物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e1510553828, createdName=124987c6m39暂无昵称, createdTime=Fri Apr 29 13:47:51 CST 2022, time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1215424, encodeId=7860121542488, content=认真***, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo6EF3hKja8nER8RMzxQdria9eCYFhgLTLsDOeqnvIYdeLDz5eP6EnicLuE5gibiawgno4zUA0jAR7Nbtp2llQ9fs3Mk/0, createdBy=278f1986883, createdName=医鸣惊人, createdTime=Thu Apr 28 19:54:11 CST 2022, time=2022-04-28, status=1, ipAttribution=)]
    2022-11-16 一闲
  6. 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time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1513479, encodeId=79c915134e996, content=<a href='/topic/show?id=8e4b2540671' target=_blank style='color:#2F92EE;'>#代谢产物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25406, encryptionId=8e4b2540671, topicName=代谢产物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e1510553828, createdName=124987c6m39暂无昵称, createdTime=Fri Apr 29 13:47:51 CST 2022, time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1215424, encodeId=7860121542488, content=认真***, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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  7. [GetPortalCommentsPageByObjectIdResponse(id=1885754, encodeId=702f1885e5411, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Mon Mar 20 00:47:51 CST 2023, time=2023-03-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1825387, encodeId=c66d182538e32, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, 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time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1513479, encodeId=79c915134e996, content=<a href='/topic/show?id=8e4b2540671' target=_blank style='color:#2F92EE;'>#代谢产物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=40, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=25406, encryptionId=8e4b2540671, topicName=代谢产物)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2e1510553828, createdName=124987c6m39暂无昵称, createdTime=Fri Apr 29 13:47:51 CST 2022, time=2022-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1215424, encodeId=7860121542488, content=认真***, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, 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  8. 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    2022-04-28 医鸣惊人

    认真***

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