Fecal Microbiome Composition Does Not Predict Diet-Induced TMAO Production in Healthy Adults

Area of Science:

• Microbiome research
• Metabolomics
• Cardiovascular disease research

Background:

• Trimethylamine-N-oxide (TMAO) is a microbial metabolite linked to cardiovascular disease.
• Plasma TMAO levels increase after red meat consumption, potentially due to gut microbe adaptation.
• Understanding the link between diet, gut microbes, and TMAO is crucial for cardiovascular health.

Purpose of the Study:

• To investigate the relationship between fecal microbial composition and plasma TMAO levels.
• To determine if known TMAO-producing bacterial genes predict TMAO levels in humans.
• To assess the correlation between microbial gene abundance and enzyme activity related to TMAO production.

Main Methods:

• A randomized crossover study involving healthy participants consuming red meat, white meat, or non-meat diets for 4 weeks each.
• Collection of fecal, plasma, and urine samples for TMAO quantitation and shotgun metagenomic sequencing.
• Measurement of fecal trimethylamine lyase activity in culture.

Main Results:

• The cai gene cluster showed a weak correlation with plasma TMAO.
• Machine learning models incorporating bacterial gene abundances did not improve TMAO prediction.
• Fecal microbial gene copy number did not accurately predict the metabolic activity of TMAO-producing enzymes.

Conclusions:

• Systemic TMAO levels are not predictable from fecal microbiome composition in this study.
• Bacterial gene abundance does not necessarily correlate with the metabolic activity of those genes.
• Further research is needed to understand the complex interplay between diet, gut microbiota, and TMAO metabolism.