Figure 1.

Graphical representation of how the intestinal microbiome might contribute to the development of pulmonary hypertension. Dietary choline and l-carnitine are catabolized to trimethylamine (TMA) by intestinal microorganisms. In the liver, TMA is metabolized to TMA N-oxide (TMAO). TMAO-treated macrophages have elevated cytokine expression and induce proliferation and migration of pulmonary artery smooth muscle cells (7), two of the hallmarks of pulmonary hypertension. TMAO also enhances platelet reactivity and increases the risk of thrombosis (3), which may contribute to the formation of in situ thrombi often seen in pulmonary hypertension lungs. However, this potential link has not been formally investigated. 3,3-dimethyl-1-butanol (DMB) inhibits microbial TMA lyase activity, thus reducing the production of TMAO, and may be beneficial in the treatment of pulmonary arterial hypertension.