An Expanded Genetic Code Enables Trimethylamine Metabolism in Human Gut Bacteria

Area of Science:

• Microbiome research
• Cardiovascular disease mechanisms
• Gut bacteria metabolism

Background:

• Animal-based diets are linked to cardiovascular disease (CVD) via trimethylamine (TMA) and trimethylamine-N-oxide (TMAO).
• Human gut bacteria possess pathways for TMA metabolism, but these are often misannotated.
• The genus *Bilophila* has unique genetic capabilities for TMA metabolism without TMAO production.

Purpose of the Study:

• To investigate the role of *Bilophila* bacteria in mitigating cardiovascular disease.
• To explore the metabolic pathways of *Bilophila* in the context of diet and TMAO production.
• To establish mechanistic links between diet, gut microbiota, and CVD development.

Main Methods:

• Meta-analysis of foundational gut microbiome studies.
• Analysis of genomic signatures for genetic code expansion in *Bilophila*.
• Assessment of *Bilophila* pathway transcription and abundance in relation to diet and CVD occurrence.

Main Results:

• The *Bilophila* demethylation pathway is actively transcribed in human gut microbiomes.
• Animal-based diets significantly increase *Bilophila* abundance.
• Higher *Bilophila* abundance showed a negative correlation with cardiovascular disease occurrence.

Conclusions:

• *Bilophila* may play a protective role in cardiovascular disease by circumventing TMAO production.
• This finding challenges the view of *Bilophila* as solely a pathobiont.
• Further research into *Bilophila* cell biology and ecology is warranted for potential biomedical applications in CVD prevention.