Mapping out the gut microbiota-dependent trimethylamine N-oxide super pathway for systems biology applications

I. M. E. Valenbreder, Sonia Balăn, Marian Breuer, Michiel Adriaens*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


The metabolic axis linking the gut microbiome and heart is increasingly being researched in the context of cardiovascular health. The gut microbiota-derived trimethylamine/trimethylamine N-oxide (TMA/TMAO) pathway is responsible along this axis for the bioconversion of dietary precursors into TMA/TMAO and has been implicated in the progression of heart failure and dysbiosis through a positive-feedback interaction. Systems biology approaches in the context of researching this interaction offer an additional dimension for deepening the understanding of metabolism along the gut-heart axis. For instance, genome-scale metabolic models allow to study the functional role of pathways of interest in the context of an entire cellular or even whole-body metabolic network. In this mini review, we provide an overview of the latest findings on the TMA/TMAO super pathway and summarize the current state of knowledge in a curated pathway map on the community platform WikiPathways. The pathway map can serve both as a starting point for continual curation by the community as well as a resource for systems biology modeling studies. This has many applications, including addressing remaining gaps in our understanding of the gut-heart axis. We discuss how the curated pathway can inform a further curation and implementation of the pathway in existing whole-body metabolic models, which will allow researchers to computationally simulate this pathway to further understand its role in cardiovascular metabolism.
Original languageEnglish
JournalFrontiers in Systems Biology
Publication statusPublished - 8 Mar 2023


  • gut microbiome
  • TMA/TMAO pathway
  • constraint-based modeling
  • gut-heart axis
  • pathway
  • whole-body metabolic model
  • heart failure

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