Trimethylamine (TMA) lyase inhibition enhances total fecal neutral sterol loss. A–F: at 8 wk of age, wild-type C57BL/6J male mice were switched from standard rodent chow to 1 of 4 experimental synthetic diets containing low (0.02%, wt/wt) or high (0.2%, wt/wt) levels of dietary cholesterol with or without the microbe-targeted TMA lyase inhibitor iodomethylcholine (IMC; 0.06%, wt/wt). After 4 wk on diets, mice were housed on wire bottom cages for a 3-day quantitative fecal collection. G–I: at 4 wk of age, apolipoprotein E-deficient (ApoE−/−) female mice were switched from standard rodent chow to a diet containing 1% supplemental choline with or without the microbe-targeted TMA lyase inhibitor IMC (0.06%, wt/wt) for 21 consecutive weeks. After 21 wk on diets, mice were housed on wire bottom cages for a 3-day quantitative fecal collection. Fecal excretion of total (G), cholesterol (H), and coprostanol (I) animal/microbial sterols (cholesterol and coprostanol) was quantified using gas-liquid chromatography. All data shown represent the means ± SE for n = 5 mice per group; *significantly different than the nondrug-treated mice within each diet group.