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Gut microbes with the gbu genes determine TMAO production from L-carnitine intake and serve as a biomarker for precision nutrition
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 , the operon, and the recently identified gene cluster, have been imp...
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Published in: | Gut microbes 2025-12, Vol.17 (1), p.2446374 |
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Main Authors: | , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
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Summary: | 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
, the
operon, and the recently identified
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
gene cluster, rather than
or the
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
genes and L-carnitine-induced TMAO production, with
showing the strongest correlation. Interestingly, these fecal
genes were found to increase with L-carnitine supplementation and decrease with a plant-based diet. Notably, we verified a previously uncultured
-containing bacterium, JAGTTR01 sp018223385, as the major contributor to TMA formation in the human gut. We isolated these
-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
-containing isolates, we developed a qPCR-based method to quantify fecal
and validated its correlation with L-carnitine-mediated TMAO production as measured by OCCT. Overall, these findings suggest that
-containing gut microbes are crucial for TMAO increases following L-carnitine intake and may serve as biomarkers or targets for personalized nutrition. |
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ISSN: | 1949-0976 1949-0984 1949-0984 |
DOI: | 10.1080/19490976.2024.2446374 |