What is SYNERGY24-TMAO
SYNERGY24-TMAO is a five-year Synergy research project, funded by the Knowledge Foundation (KK-stiftelsen) and hosted at Örebro University, that aims to elucidate how the dietary metabolite Trimethylamine N-oxide (TMAO) acts as a shared driver of disease mechanisms across three highly prevalent chronic inflammatory diseases: cardiovascular disease (CVD), chronic kidney disease (CKD), and periodontitis.
These diseases represent a major burden to global health and healthcare systems and frequently coexist in the same individuals. While traditionally studied as separate conditions, emerging evidence suggests that they share common inflammatory, metabolic, and microbial pathways. TMAO, a gut microbiota–derived metabolite formed from dietary nutrients such as choline and carnitine, has been implicated in systemic inflammation, endothelial dysfunction, fibrosis, and tissue damage. However, the molecular mechanisms, context-dependent effects, and key intervention points of TMAO across organ systems remain insufficiently understood.
SYNERGY24-TMAO addresses this critical knowledge gap by integrating clinical data, mechanistic experimental models, preclinical validation, and advanced multi-omics approaches to provide a unified understanding of how TMAO contributes to chronic inflammatory disease progression.
Core question
Can the dietary metabolite Trimethylamine N-oxides (TMAO) be the common pathophysiologic denominator between chronic inflammatory diseases?
The subprojects in relation to the core question
The project is organized into four interconnected subprojects (SP1–SP4), each addressing a critical dimension of the core question while contributing to a unified framework.
SP1 – Clinical cohorts
SP1 examines associations between circulating TMAO levels, disease severity, and outcomes in clinical cohorts with CVD, CKD, and periodontitis, using clinical data and multi-omics profiling to identify shared and disease-specific TMAO signatures.
SP2 – In vitro mechanisms
SP2 dissects the cellular and molecular mechanisms by which TMAO regulates inflammation, immune responses, and tissue remodelling using controlled in vitro models and high-resolution omics analyses.
SP3 – In vivo validation
SP3 validates mechanistic findings in preclinical in vivo models to assess systemic and organ-specific effects of TMAO and to test targeted interventions.
SP4 – Integration and knowledge transfer
SP4 integrates clinical and experimental data using systems biology and predictive modelling to identify shared pathways, biomarkers, and translational opportunities.
