title: Alteration of gut bacteria and metabolomes after glucaro-1,4-lactone treatment contributes to the prevention of hypercholesterolemia.
abstract: D-Glucaro-1,4-lactone (1,4-GL) has been shown to have a hypocholesterolemic effect in rats and human subjects. However, little information is known concerning the alteration of metabolome associated with the effect. Here, we show that 1,4-GL delays the development of hypercholesterolemia with the coadministration of a high-fat, high-cholesterol diet (HFHC) in rats. Metabonomic results based on proton nuclear magnetic resonance indicate that urinary trimethylamine N-oxide, trimethylamine, lactate, acetate, formate, and creatinine are significantly altered after 1,4-GL and HFHC treatments. Colonic flora test results reveal that the quantity of Bifidobacterium and Lactobacillus in the intestines respectively increase by about 1.7- and 4.2-fold in rats treated with 1,4-GL compared with those in the control group. Rats that were coadministered with HFHC and 1,4-GL exhibit normal levels of lactate and acetate in serum and display urinary excretions of lactate and acetate that are 2 to 3 times higher compared with those treated with HFHC alone. The results imply that the increased probiotic quantities and urinary excretion of breakdown products of fat/cholesterol after 1,4-GL treatment contribute to the prevention of hypercholesterolemia. Our study offers insights into the model of action for 1,4-GL in preventing hypercholesterolemia.
authors: School of Pharmacy, Nanchang University , Nanchang, 330006, People's Republic of China.
authors: Baogang
authors: B
authors: Xie
authors: Aihong
authors: A
authors: Liu
authors: Xuejun
authors: X
authors: Zhan
authors: Xinming
authors: X
authors: Ye
authors: Jing
authors: J
authors: Wei
mesh_terms: D000818:Animals; D001644:Bifidobacterium; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000009:adverse effects; D003404:Creatinine / Q000652:urine; D059305:Diet, High-Fat / Q000009:adverse effects; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005937:Glucaric Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006937:Hypercholesterolemia / Q000097:blood / Q000517:prevention & control*; D007778:Lactobacillus; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D055442:Metabolome / Q000187:drug effects*; D008744:Methylamines; D019936:Probiotics / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
chemical_list: D002791:Cholesterol, Dietary; D008744:Methylamines; D014280:Triglycerides; C009194:saccharolactone; D003404:Creatinine; C005855:trimethyloxamine; D005937:Glucaric Acid