Gut microbes with the gbu genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition.

IF 12.2 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Wei-Kai Wu,Yi-Ling Lo,Jian-Ying Chiu,Chia-Lang Hsu,I-Hsuan Lo,Suraphan Panyod,Yu-Chieh Liao,Tina H T Chiu,Yu-Tang Yang,Han-Chun Kuo,Hsin-Bai Zou,Yi-Hsun Chen,Hsiao-Li Chuang,Jeffrey J Y Yen,Jin-Town Wang,Han-Mo Chiu,Cheng-Chih Hsu,Ching-Hua Kuo,Lee-Yan Sheen,Hsien-Li Kao,Ming-Shiang Wu
{"title":"Gut microbes with the gbu genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition.","authors":"Wei-Kai Wu,Yi-Ling Lo,Jian-Ying Chiu,Chia-Lang Hsu,I-Hsuan Lo,Suraphan Panyod,Yu-Chieh Liao,Tina H T Chiu,Yu-Tang Yang,Han-Chun Kuo,Hsin-Bai Zou,Yi-Hsun Chen,Hsiao-Li Chuang,Jeffrey J Y Yen,Jin-Town Wang,Han-Mo Chiu,Cheng-Chih Hsu,Ching-Hua Kuo,Lee-Yan Sheen,Hsien-Li Kao,Ming-Shiang Wu","doi":"10.1080/19490976.2024.2446374","DOIUrl":null,"url":null,"abstract":"Gut microbial metabolism of L-carnitine, which leads to the production of detrimental trimethylamine N-oxide (TMAO), offers a plausible link between red meat consumption and cardiovascular risks. Several microbial genes, including cntA/B, the cai operon, and the recently identified gbu gene cluster, have been implicated in the conversion of dietary L-carnitine into TMA(O). However, the key microbial genes and associated gut microbes involved in this pathway have not been fully explored. Utilizing the oral carnitine challenge test (OCCT), which specifically measures TMAO production from L-carnitine intake and identifies TMAO producer phenotypes, we compared the abundance of microbial genes between low- and high-TMAO producers across three independent cohorts. Our findings consistently revealed that the gbu gene cluster, rather than cntA/B or the cai operon, was significantly enriched in high-TMAO producers. We further analyzed 292 paired multi-omic datasets from OCCT and shotgun metagenomic sequencing, which demonstrated a significant positive correlation between the abundance of fecal gbu genes and L-carnitine-induced TMAO production, with gbuB showing the strongest correlation. Interestingly, these fecal gbu genes were found to increase with L-carnitine supplementation and decrease with a plant-based diet. Notably, we verified a previously uncultured gbu-containing bacterium, JAGTTR01 sp018223385, as the major contributor to TMA formation in the human gut. We isolated these gbu-containing gut microbes and confirmed their role in TMA/TMAO production using anaerobic incubation and a gnotobiotic mouse model. Using an in-house collection of gbu-containing isolates, we developed a qPCR-based method to quantify fecal gbuB and validated its correlation with L-carnitine-mediated TMAO production as measured by OCCT. Overall, these findings suggest that gbu-containing gut microbes are crucial for TMAO increases following L-carnitine intake and may serve as biomarkers or targets for personalized nutrition.","PeriodicalId":12909,"journal":{"name":"Gut Microbes","volume":"25 1","pages":"2446374"},"PeriodicalIF":12.2000,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Gut Microbes","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/19490976.2024.2446374","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Gut microbial metabolism of L-carnitine, which leads to the production of detrimental trimethylamine N-oxide (TMAO), offers a plausible link between red meat consumption and cardiovascular risks. Several microbial genes, including cntA/B, the cai operon, and the recently identified gbu gene cluster, have been implicated in the conversion of dietary L-carnitine into TMA(O). However, the key microbial genes and associated gut microbes involved in this pathway have not been fully explored. Utilizing the oral carnitine challenge test (OCCT), which specifically measures TMAO production from L-carnitine intake and identifies TMAO producer phenotypes, we compared the abundance of microbial genes between low- and high-TMAO producers across three independent cohorts. Our findings consistently revealed that the gbu gene cluster, rather than cntA/B or the cai operon, was significantly enriched in high-TMAO producers. We further analyzed 292 paired multi-omic datasets from OCCT and shotgun metagenomic sequencing, which demonstrated a significant positive correlation between the abundance of fecal gbu genes and L-carnitine-induced TMAO production, with gbuB showing the strongest correlation. Interestingly, these fecal gbu genes were found to increase with L-carnitine supplementation and decrease with a plant-based diet. Notably, we verified a previously uncultured gbu-containing bacterium, JAGTTR01 sp018223385, as the major contributor to TMA formation in the human gut. We isolated these gbu-containing gut microbes and confirmed their role in TMA/TMAO production using anaerobic incubation and a gnotobiotic mouse model. Using an in-house collection of gbu-containing isolates, we developed a qPCR-based method to quantify fecal gbuB and validated its correlation with L-carnitine-mediated TMAO production as measured by OCCT. Overall, these findings suggest that gbu-containing gut microbes are crucial for TMAO increases following L-carnitine intake and may serve as biomarkers or targets for personalized nutrition.
带有gbu基因的肠道微生物决定了摄入左旋肉碱产生的氧化三甲胺,并作为精确营养的生物标志物。
左旋肉碱的肠道微生物代谢会导致有害的三甲胺n -氧化物(TMAO)的产生,这为红肉消费与心血管风险之间的联系提供了一种合理的联系。一些微生物基因,包括cntA/B、cai操纵子和最近发现的gbu基因簇,都与膳食中左旋肉碱转化为TMA(O)有关。然而,参与这一途径的关键微生物基因和相关肠道微生物尚未被充分探索。利用口服肉毒碱激发试验(OCCT),专门测量左旋肉碱摄入产生的氧化三甲胺并确定氧化三甲胺产生者表型,我们比较了三个独立队列中低氧化三甲胺产生者和高氧化三甲胺产生者之间微生物基因的丰度。我们的研究结果一致表明,gbu基因簇,而不是cntA/B或cai操纵子,在高tmao生产者中显著富集。我们进一步分析了来自OCCT和霰弹枪宏基因组测序的292对多组数据集,结果表明粪便gbu基因丰度与左旋肉碱诱导的TMAO产生显著正相关,其中gbuB的相关性最强。有趣的是,这些粪便gbu基因被发现在补充左旋肉碱时增加,而在植物性饮食中减少。值得注意的是,我们证实了先前未培养的含ggu的细菌JAGTTR01 sp018223385是人类肠道中TMA形成的主要贡献者。我们分离了这些含ggu的肠道微生物,并通过厌氧培养和非生物小鼠模型证实了它们在TMA/TMAO生产中的作用。利用内部收集的含有gbuB的分离株,我们开发了一种基于qpcr的方法来量化粪便gbuB,并验证了其与OCCT测量的左旋肉碱介导的TMAO产生的相关性。总的来说,这些发现表明,含ggu的肠道微生物对左旋肉碱摄入后氧化三甲胺的增加至关重要,可能作为个性化营养的生物标志物或目标。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Gut Microbes
Gut Microbes Medicine-Microbiology (medical)
CiteScore
18.20
自引率
3.30%
发文量
196
审稿时长
10 weeks
期刊介绍: The intestinal microbiota plays a crucial role in human physiology, influencing various aspects of health and disease such as nutrition, obesity, brain function, allergic responses, immunity, inflammatory bowel disease, irritable bowel syndrome, cancer development, cardiac disease, liver disease, and more. Gut Microbes serves as a platform for showcasing and discussing state-of-the-art research related to the microorganisms present in the intestine. The journal emphasizes mechanistic and cause-and-effect studies. Additionally, it has a counterpart, Gut Microbes Reports, which places a greater focus on emerging topics and comparative and incremental studies.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信