PFAS Biliary Excretion Pathway
The liver is a primary PFAS target organ, and hepatic clearance through bile is an important PFAS elimination pathway. PFAS secreted into bile by hepatic transporters (particularly MRP2) are concentrated in the gallbladder, where bile storage results in higher PFAS concentrations than in circulating blood. The gallbladder’s epithelial cells and the bile itself accumulate PFAS before release into the duodenum.
This biliary concentration mechanism means the gallbladder is exposed to PFAS at higher levels than most other tissues. PFAS in bile are also subject to enterohepatic recirculation — reabsorption from the small intestine and return to hepatic circulation — which maintains high PFAS levels in the biliary system over time.
PFAS and Gallbladder Disease Risk
Epidemiological studies have found associations between PFAS serum levels and gallbladder disease, including cholecystitis and cholelithiasis (gallstones). The Nurses’ Health Study found that women with higher PFAS quartiles had modestly elevated rates of cholecystectomy (gallbladder removal surgery) — a marker of symptomatic gallbladder disease.
Proposed mechanisms include PFAS-induced alterations in bile acid composition and cholesterol metabolism that promote gallstone formation, and PFAS-induced gallbladder epithelial inflammation that facilitates cholecystitis. PFAS-activated PPARα in gallbladder epithelial cells may alter the lipid composition of bile in ways that favor cholesterol precipitation.
Gastroenterological Relevance
Gastroenterologists and surgeons evaluating patients for cholecystitis or evaluating whether cholecystectomy is indicated may benefit from noting environmental PFAS exposure as a potential contributing factor, particularly in younger patients with gallbladder disease — a population where environmental contributors are more likely relevant than age-related degenerative changes.
Dietary approaches that support bile flow and gallbladder function — adequate dietary fat to stimulate gallbladder contraction, adequate hydration, and avoidance of rapid weight cycling — are reasonable alongside PFAS exposure reduction for patients with gallbladder disease in contaminated areas.