For a long time, doctors have assumed that the lipids that cause atherosclerosis came from fatty, cholesterol-rich food. Yet researchers at the University of Connecticut (UConn) have found lipids with a chemical signature that doesn’t resemble lipids that come from animals. Instead, they come from the Bacteroidetes family of bacteria, which typically resides in the mouth and gastrointestinal tract.
“I always call them greasy bugs because they make so much lipid. They are constantly shedding tiny blebs of lipids. Looks like bunches of grapes,” said Frank Nichols, DDS, PhD, a UConn Health periodontist who studies the links between gum disease and atherosclerosis.
Bacteroidetes makes distinctive fats. The molecules have unusual fatty acids with branched chains and odd numbers of carbons. Typically, mammals don’t make branched chain fatty acids or fatty acids with odd numbers of carbons. The chemical differences between these bacterial lipids and human lipids result in subtle weight differences between the molecules.
“We used these weight differences and modern mass spectrometers to selectively measure the quantity of the bacterial lipids in human samples to link the lipids to atherosclerosis,” said Xudong Yao, PhD, MS, a UConn associate professor of chemistry who analyzed the lipid samples. “Establishment of such a link is a first step to mark the lipids as indicators for early disease diagnosis.”
The marked chemical differences between Bacteroidetes lipids and the human body’s native lipids may be the reason they cause disease, suggests Nichols. The immune cells that initially stick to the blood vessel walls and collect the lipids recognize them as foreign. These immune cells react to the lipids and set off alarms, inflaming and thickening the blood vessel walls, creating plaques, clogs, and atheromas.
Despite being non-native lipids, the Bacteroidetes lipids could be broken down by an enzyme in the body that processes lipids into the starting material to make inflammation-enhancing molecules. So, the Bacteroidetes lipids damage blood vessels in two ways: the immune system sees them as a signal of bacterial invasion, and then enzymes break them down and super-charge the inflammation.
The researchers note that Bacteroidetes is not an invading species, as it usually remains in the oral cavity and in the gastrointestinal tract. If conditions are right, it can cause gum disease but not infect the blood vessels. However, the lipids it produces also pass easily through cell walls and into the bloodstream.
Next, the researchers will analyze thin slices of atheroma to localize exactly where the bacterial lipids are accumulating. If the Bacteroidetes-specific lipids are accumulating within the atheroma but not in the normal artery wall, the researchers believe, it would be convincing evidence that these unusual lipids are associated specifically with atheroma formation and therefore contribute to heart disease.