Metagenomic analysis of gut microbiota reveals its role in trimethylamine metabolism in heart failure

Takuo Emoto, Tomohiro Hayashi, Tokiko Tabata, Tomoya Yamashita, Hikaru Watanabe, Tomoya Takahashi, Yasuhiro Gotoh, Kenjiro Kami, Naofumi Yoshida, Yoshihiro Saito, Hidekazu Tanaka, Kensuke Matsumoto, Tetsuya Hayashi, Takuji Yamada, Ken ichi Hirata

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)


Background: We had previously reported an increase in trimethylamine N-oxide (TMAO) levels in patients with both compensated and decompensated heart failure (HF) and alteration in gut microbiota composition using 16S rRNA gene amplicon analysis. Although a metagenome-wide analysis showed that choline-TMA lyase levels increased in HF patients, which TMA generation pathway from choline, carnitine, or betaine contributes to the increase in TMAO levels in HF needs to be elucidated. Methods: We conducted a metagenome-wide shotgun sequencing analysis of gut microbiota and measured the TMAO levels in plasma of 22 HF patients during the compensated phase and 11 age-, sex-, and comorbidity-matched control subjects, whose gut microbiota compositions were reported in a previous 16S rRNA-based analysis. Results: The abundance of cntA/B was positively correlated with TMAO, especially in HF patients, whereas that of cutC/D or betaine reductase was not correlated either in controls or HF patients. The abundance of cntA/B was mainly derived from the genera Escherichia and Klebsiella either in controls or HF patients. Conclusion: TMAO levels in plasma depend on the abundance of cntA/B in HF. Although it is difficult to exclude the involvement of confounding factors, microbial dysbiosis connecting the abundance of cntA/B in the gut and the increase of TMAO in plasma can be a therapeutic target for HF.

Original languageEnglish
Pages (from-to)138-142
Number of pages5
JournalInternational Journal of Cardiology
Publication statusPublished - Sept 1 2021

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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