Dr. Amy Nett: Great question and probably kind of a complicated question. Essentially multiple studies over at least the past 15 years have shown associations between infections, including bacterial infections like Chlamydia pneumoniae, Helicobacter pylori, also viral infections like herpes virus, cytomegalovirus, and increases in lipids, including LDL and probably triglycerides as well. For example, there is one study, at least, that I’m aware of that did show Helicobacter pylori leads to elevated levels of total cholesterol, LDL, lipoprotein(a), ApoB, and LDL particle number and also increased triglycerides and potentially decreased HDL. Essentially we’re seeing an unfavorable lipid profile in response to Helicobacter pylori. It’s very clear that chronic infection does affect the lipid profile.
As to the mechanism, well, several mechanisms have been proposed to explain the association between infections and this dyslipidemia. Some of the evidence suggests that viral and bacterial infections directly alter lipid metabolism of the infected cell and that potentially some of the bacterial metabolism can itself produce triglycerides as a byproduct of their metabolism. Other evidence suggests that lipids actually increase as a result of the body’s attempt to fight off the infection. Still more evidence suggests that LDL may actually have antimicrobial properties and is directly involved in inactivating microbial pathogens. This has been confirmed with studies that show mice with defective LDL receptors—and, therefore, very high levels of LDL—are protected against infection by gram-negative bacteria, just like Helicobacter pylori is a gram-negative bacterium. So multiple different mechanisms that may cause an elevation in LDL, elevation in total cholesterol or triglycerides when we have chronic infection.
There’s actually an interesting article in the journal Nature called “Cholesterol, Iinflammation and Iinnate Iimmunity.” I thought this one was interesting because it shows that, yes, the inflammatory response does increase LDL, probably due to its beneficial effects in response to infection, but that this elevation probably then worsens the diseases associated with chronic metabolic inflammation, including atherosclerosis, because the high cholesterol potentially further augments the high cholesterol. What I mean by that is when you have high blood cholesterol, you have an accumulation of cholesterol in the macrophages and in other immune cells, which further promotes the inflammatory response, and this includes an augmentation of the toll-like receptor signaling. It also includes inflammasome activation and the production of monocytes and neutrophils. Activation, then, of the toll-like receptor signaling then leads to a decrease in cholesterol efflux, which results in further accumulation of the amplification of the inflammatory response, so you have chronic infection leading to an increased LDL through different pathways, but then you also have the amplification due to the changes in cellular signalling and namely this activation of toll-like receptor signaling. That’s another way that having chronic infection is probably going to be increasing the LDL, increasing oxidized LDL, and sort of worsening those metabolic parameters.
Hopefully that answers the question in terms of how the gut infections contribute to raised cholesterol. It’s really not the microbiome that contributes. It’s when you have chronic infection, and a common cause of chronic infection is dysbiosis or GI infection.