Gut microbiota-derived metabolite Trimethylamine-N-oxide (TMAO) and multiple health outcomes: an umbrella review and updated meta-analysis

Doudou Li, Ying Lu, Shuai Yuan, Xiaxia Cai, Yuan He, Jie Chen, Qiong Wu, Di He, Aiping Fang, Yacong Bo, Peige Song, Debby Bogaert, Konstantinos K Tsilidis, Susanna C. Larsson, Huanling Yu, Huilian Zhu, Evropi Theodoratou, Yimin Zhu, Xue Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

BACKGROUND: Trimethylamine-N-oxide (TMAO) is a gut microbiota-derived metabolite produced from dietary nutrients. Many studies have discovered that circulating TMAO concentrations are linked to a wide range of health outcomes.

OBJECTIVES: This study aimed to summarize health outcomes related to circulating TMAO concentrations.

METHODS: We searched the Embase, Medline, Web of Science, and Scopus databases from inception to 15 February, 2022 to identify and update meta-analyses examining the associations between TMAO and multiple health outcomes. For each health outcome, we estimated the summary effect size, 95% prediction CI, between-study heterogeneity, evidence of small-study effects, and evidence of excess-significance bias. These metrics were used to evaluate the evidence credibility of the identified associations.

RESULTS: This umbrella review identified 24 meta-analyses that investigated the association between circulating TMAO concentrations and health outcomes including all-cause mortality, cardiovascular diseases (CVDs), diabetes mellitus (DM), cancer, and renal function. We updated these meta-analyses by including a total of 82 individual studies on 18 unique health outcomes. Among them, 14 associations were nominally significant. After evidence credibility assessment, we found 6 (33%) associations (i.e., all-cause mortality, CVD mortality, major adverse cardiovascular events, hypertension, DM, and glomerular filtration rate) to present highly suggestive evidence.

CONCLUSIONS: TMAO might be a novel biomarker related to human health conditions including all-cause mortality, hypertension, CVD, DM, cancer, and kidney function. Further studies are needed to investigate whether circulating TMAO concentrations could be an intervention target for chronic disease.This review was registered at as CRD42021284730.

Original languageEnglish
Pages (from-to)230-243
JournalThe American Journal of Clinical Nutrition (AJCN)
Issue number1
Early online date28 Mar 2022
Publication statusPublished - 6 Jul 2022

Keywords / Materials (for Non-textual outputs)

  • TMAO
  • all-cause mortality
  • cardiovascular disease
  • diabetes mellitus
  • hypertension
  • trimethylamine-N-oxide
  • umbrella review
  • updated meta-analyses


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