Nutrient Absorption in Lean Versus Obese Individuals

我们最初的研究检测了两种标准饮食(2400千卡/天和3400千卡/天)的肥胖者和瘦肉者的粪便和尿液能量损失。 最初的14名瘦身者和9名肥胖者的初步结果没有显示出大便或尿液能量损失的任何差异。两组的大便卡路里范围都很大，从2%到9%不等。与肥胖的人相比，瘦的人在高卡路里的饮食中吸收更多(大便能量损失更少)。主要肠道系统类型Firimutes和拟杆菌的百分比变化与营养负荷的变化有关。菌丝体百分比随营养负荷的增加而增加，类杆菌数随营养物负荷的增加而减少。此外，在瘦肉个体中，主要种型的这些变化与大便能量损失有关，因此，Firmcutes/Bacteroidetes增加或减少20%与大便能量损失约150千卡/天相关。 内源性大麻素系统最近被认为与肠道通透性的调节有关，从而影响营养物质的吸收。我们调查了循环中内源性大麻素、花生胺(AEA)和2-花生四烯酸甘油(2-AG)的浓度是否与大便热量损失有关。我们发现，较高的营养负荷会降低瘦人而不是肥胖者的AEA浓度。AEA也与肥胖但不瘦的个体更大的营养吸收(大便中较少的卡路里损失)有关。这可能表明内源性大麻素系统在肠道养分吸收中的作用。 在前期工作的基础上，我们设计了一项新的研究来证实和推广这些发现。在这项研究中，我们将测量喂养过多和喂养不足期间的粪便能量损失和肠道微生物区系的变化(根据计算的体重维持卡路里分别为150%和50%)。之后，志愿者将被随机接受抗生素口服万古霉素和安慰剂(双盲随机方式)。口服万古霉素在健康人体内不被吸收，会选择性地改变肠道细菌种群。这将使我们能够调查肠道微生物区系的变化与营养收获(通过粪便能量损失衡量)之间是否存在关联。我们还将研究肠道微生物区系的变化如何影响葡萄糖耐量、能量消耗和底物氧化。我们目前已经招募了计划中的24名参与者中的19名参与这项研究。

Our initial study examined stool and urine energy losses in obese versus lean individuals on two standard (2400 kcal/d and 3400 kcal/d each given over 3 days) diets. Preliminary results from an initial 14 lean and 9 obese individuals failed to show any difference in stool or urine energy loss. The range of calories stool was large, varying from 2 to 9 % in both groups. Lean individuals absorbed more (had less stool energy loss) on the higher calorie diet compared to obese individuals. Percent changes in the major gut phylotypes, Firimutes and Bacteroidetes, were associated with changes in nutrient load. Percent of Firmicutes increased with nutrient load while Bacteroidetes decreased. In addition, in lean individuals, these changes in the major phylotypes were associated with stool energy loss, such that a 20% increase or decrease in Firmcutes/Bacteroidetes was associated with approximately 150 kcal/day difference in stool energy loss. The endocannabinoid system has recently been implicated in regulation of gut permeability and thus nutrient absorption. We investigated whether the concentrations of the circulating endocannabinoids, anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are associated with stool calories loss. We found that higher nutrient load reduced AEA concentrations in lean but not obese individuals. AEA was also associated with greater nutrient absorption (less calories loss in stool) in obese but not lean individuals. This may indicate a role for the endocannabinoid system in intestinal nutrient absorption. Based on this preliminary work, we have designed a new study to confirm and extend these findings. In this study, stool energy loss and changes in gut microbiota will be measured during over and underfeeding (150 and 50% based on calculated weight maintaining calories). Following this, volunteers will be randomized to receive the antibiotic oral vancomycin versus placebo (in a double blind randomized fashion). Oral vancomycin is not absorbed in healthy individuals and will selectively change the gut bacterial population. This will allow us to investigate whether there is an association between changes in gut microbiota and nutrient harvest (as measured by stool energy loss). We will also investigate how changes in the gut microbiota affect glucose tolerance, energy expenditure and substrate oxidation. We currently have enrolled 19 of planned 24 participants in this study.