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

Abstract

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
Article number1074749
JournalFrontiers in Systems Biology
Volume3
DOIs
Publication statusPublished - 8 Mar 2023

Keywords

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

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