A chemical called trimethylamine N-oxide (TMAO), which originates from gut bacteria digesting animal products such as red meat, is present at higher levels in the blood of people with an irregular heart beat than the rest of the population.
The researchers found that after they had controlled for various factors like age and comorbidities, people in the top third of TMAO levels had a 70% increased risk of having atrial fibrillation compared with those in the bottom third.
Atrial fibrillation is the most common sustained heart rhythm disorder in the U.S. impacting more than 10 million adults. It occurs because the upper chambers of the heart beat rapidly and irregularly, which can lead to blood clots, stroke and heart failure if left unchecked.
TMAO is formed when trimethylamine produced by gut bacteria is carried to the liver and oxidized. Animal-derived foods such as red and processed meat, eggs, high fat dairy products, and some supplements, are the main dietary precursors for production of TMAO. It has previously been linked to increased risk of cardiovascular disease more generally, but whether high levels of this chemical increased risk of atrial fibrillation was less clear.
In this study, published in the journal of Journal of Clinical Investigation, lead investigator Robert Koeth, MD, PhD, a clinician scientist based at the Cleveland Clinic, and colleagues assessed blood TMAO levels in 5,000 adults who underwent elective heart catheterization for known or suspected cardiovascular disease.
They also studied the effects of TMAO on heart beat regularity in model mice susceptible to atrial fibrillation and tested a potential candidate drug to see if it could reduce levels of TMAO in these animals.
After controlling for age, sex, diabetes, cardiovascular disease, blood pressure, smoking, body mass index, inflammation and kidney function, people with the highest TMAO levels had about 1.7‑times the odds of having atrial fibrillation compared with people with the lowest levels.
In the mouse studies, when TMAO levels in the blood were higher, the animals developed atrial fibrillation sooner and it became a persistent problem more quickly. The researchers also saw changes in how electrical signals moved through parts of the heart that made it easier for abnormal rhythms to start and continue.
The researchers tested iodomethylcholine in the mice, an experimental small molecule drug that blocks the gut microbial enzyme responsible for converting choline into trimethylamine. In response to the drug, TMAO levels fell, the mix of gut bacteria changed, and both the first episodes of atrial fibrillation and its progression were delayed without notable negative effects on the liver.
“A possible pathogenic culprit for the development of atrial myopathy and electromechanical dysfunction is chronic autonomic dysfunction from TMAO inhibition of the M2 muscarinic acetylcholine receptor and increasing sympathetic tone,” write Koeth and team.
The results suggest “TMAO promotes atrial fibrillation in a gut microbiota dependent manner by causing autonomic dysfunction, atrial myopathy, and electromechanical dysfunction,” they conclude.
The post Gut Bacteria Chemical Linked to Irregular Heart Beat appeared first on Inside Precision Medicine.