Baumgartner S, Reijnders D, Konings M C J M, Groen A K, Lütjohann D, Goossens G H, Blaak E E, Plat J
Department of Human Biology and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229 ER, Maastricht, The Netherlands.
Department of Human Biology and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, 6229 ER, Maastricht, The Netherlands; Top Institute Food and Nutrition, 6700 AN, Wageningen, The Netherlands.
Chem Phys Lipids. 2017 Oct;207(Pt B):239-245. doi: 10.1016/j.chemphyslip.2017.06.006. Epub 2017 Jun 21.
Changes in the microbiota composition have been implicated in the development of obesity and type 2 diabetes. However, not much is known on the involvement of gut microbiota in lipid and cholesterol metabolism. In addition, the gut microbiota might also be a potential source of plasma oxyphytosterol and oxycholesterol concentrations (oxidation products of plant sterols and cholesterol). Therefore, the aim of this study was to modulate the gut microbiota by antibiotic therapy to investigate effects on parameters reflecting cholesterol metabolism and oxyphytosterol concentrations.
A randomized, double blind, placebo-controlled trial was performed in which 55 obese, pre-diabetic men received oral amoxicillin (broad-spectrum antibiotic), vancomycin (antibiotic directed against Gram-positive bacteria) or placebo (microcrystalline cellulose) capsules for 7days (1500mg/day). Plasma lipid and lipoprotein, non-cholesterol sterol, bile acid and oxy(phyto)sterol concentrations were determined at baseline and after 1-week intervention.
Plasma secondary bile acids correlated negatively with cholestanol (marker for cholesterol absorption, r=-0.367; P<0.05) and positively with lathosterol concentrations (marker for cholesterol synthesis, r=0.430; P<0.05). Fasting plasma secondary bile acid concentrations were reduced after vancomycin treatment as compared to placebo treatment (-0.24±0.22μmol/L vs. -0.08±0.29μmol/L; P<0.01). Vancomycin and amoxicillin treatment did not affect markers for cholesterol metabolism, plasma TAG, total cholesterol, LDL-C or HDL-C concentrations as compared to placebo. In addition, both antibiotic treatments did not affect individual isoforms or total plasma oxyphytosterol or oxycholesterol concentrations.
Despite strong correlations between plasma bile acid concentrations and cholesterol metabolism (synthesis and absorption), amoxicillin and vancomycin treatment for 7days did not affect plasma lipid and lipoprotein, plasma non-cholesterol sterol and oxy(phyto)sterol concentrations in obese, pre-diabetic men.
微生物群组成的变化与肥胖症和2型糖尿病的发生有关。然而，关于肠道微生物群在脂质和胆固醇代谢中的作用，人们了解得并不多。此外，肠道微生物群也可能是血浆氧植物甾醇和氧胆固醇浓度（植物甾醇和胆固醇的氧化产物）的潜在来源。因此，本研究的目的是通过抗生素治疗调节肠道微生物群，以研究其对反映胆固醇代谢和氧植物甾醇浓度参数的影响。
进行了一项随机、双盲、安慰剂对照试验，55名肥胖的糖尿病前期男性接受口服阿莫西林（广谱抗生素）、万古霉素（针对革兰氏阳性菌的抗生素）或安慰剂（微晶纤维素）胶囊，为期7天（1500毫克/天）。在基线和1周干预后测定血浆脂质和脂蛋白、非胆固醇甾醇、胆汁酸和氧（植物）甾醇浓度。
血浆次级胆汁酸与胆甾烷醇（胆固醇吸收标志物，r = -0.367；P < 0.05）呈负相关，与羊毛甾醇浓度（胆固醇合成标志物，r = 0.430；P < 0.05）呈正相关。与安慰剂治疗相比，万古霉素治疗后空腹血浆次级胆汁酸浓度降低（-0.24±0.22微摩尔/升对-0.08±0.29微摩尔/升；P < 0.01）。与安慰剂相比，万古霉素和阿莫西林治疗对胆固醇代谢标志物、血浆甘油三酯、总胆固醇、低密度脂蛋白胆固醇或高密度脂蛋白胆固醇浓度没有影响。此外，两种抗生素治疗均未影响个体异构体或血浆氧植物甾醇或氧胆固醇的总浓度。
尽管血浆胆汁酸浓度与胆固醇代谢（合成和吸收）之间存在很强的相关性，但为期7天的阿莫西林和万古霉素治疗并未影响肥胖的糖尿病前期男性的血浆脂质和脂蛋白、血浆非胆固醇甾醇和氧（植物）甾醇浓度。
