Gut microbes with the gbu genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition
Year: 2024
Type: article
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.
Source: Gut Microbes
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
Language: English
Topic: Gut microbiota and health
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $3,060
Awards: Establishment of Standard Gut-Heart Axis Examination and Drug Discovery Platform in Developing Microbiome Diagnostic Tools and Clinical Therapeutics( II ), Bioinformatics Core Facility for Biotechnology and Pharmaceuticals, Establishment of Standard Gut-Heart Axis Examination and Drug Discovery Platform in Developing Microbiome Diagnostic Tools and Clinical Therapeutics( I ), Establishment of Standard Gut-Heart Axis Examination and Drug Discovery Platform in Developing Microbiome Diagnostic Tools and Clinical Therapeutics( III )
OpenAlex ID: W4405794166