COMMENTARY

The Gut-Liver Axis and NAFLD: Clarifying the Link

William F. Balistreri, MD

Disclosures

December 11, 2013

In This Article

The Choline Connection

There may also be a link to other dietary constituents. An analogy has been drawn between microbial impact on atherosclerosis and adverse intrahepatic events. Atherosclerosis has long been recognized to be partially driven by inflammation, and the gut metagenome appears to contribute to this inflammatory milieu. Studies in animals have documented the mechanistic link between intestinal microbial metabolism of the choline moiety of ingested phosphatidylcholine (lecithin) and coronary artery disease.[19]

Choline-containing nutrients that reach the cecum and large bowel may serve as fuel for the gut microbiota, producing trimethylamine (TMA), which is rapidly oxidized to trimethylamine-N-oxide (TMAO). TMAO enhances the accumulation of cholesterol in macrophages and the accumulation of foam cells in artery walls, leading to an increased risk for cardiovascular disease.[19]

An analogous mechanism is probably a contributing factor to NAFLD -- microbial conversion of choline into TMA reduces the bioavailability of choline. This allows an influx of fatty acids to the liver, where generation of radical oxidative species from fatty acids leads to oxidative stress.[20]

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