Nutrient Absorption in Lean Versus Obese Individuals

我们最初的研究检查了两种标准饮食（2400千卡/天和3400千卡/天，每种饮食持续3天）下肥胖与瘦型个体的粪便和尿液能量损失。 最初的14个瘦的和9个肥胖的个体的初步结果没有显示出粪便或尿液能量损失的任何差异。两组粪便的热量范围很大，从2%到9%不等。与肥胖个体相比，瘦个体在高热量饮食中吸收更多（粪便能量损失较少）。 主要的肠道菌群类型，Firimutes和Bacteroidetes的百分比变化与营养负荷的变化有关。 厚壁菌门的百分比随着营养负荷的增加而增加，拟杆菌门的百分比随着营养负荷的增加而减少。此外，在偏瘦的个体中，主要粪便类型的这些变化与粪便能量损失相关，例如，Firmcutes/拟杆菌增加或减少20%与粪便能量损失的约150 kcal/天差异相关。 内源性大麻素系统最近被认为与调节肠道通透性和营养吸收有关。我们研究了循环内源性大麻素，大麻素（AEA）和2-花生四烯酰甘油（2-AG）的浓度是否与粪便热量损失有关。我们发现，较高的营养负荷减少AEA浓度在瘦，但不肥胖的人。AEA还与肥胖但不瘦个体的更大营养吸收（粪便中损失的卡路里更少）相关。这可能表明内源性大麻素系统在肠道营养吸收中的作用。 基于这些初步工作，我们设计了一项新的研究来证实和扩展这些发现。 在这项研究中，将在过度和喂养不足期间测量粪便能量损失和肠道微生物群的变化（基于计算的体重维持卡路里的150%和50%）。之后，志愿者将随机接受抗生素口服万古霉素与安慰剂。 口服万古霉素在健康个体中不被吸收，并且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群的变化与营养收获之间是否存在关联（通过粪便能量损失来衡量）。我们还将研究肠道微生物群的变化如何影响葡萄糖耐量，能量消耗和底物氧化。这项研究预计将在未来几个月内开始招募。

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. 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. This study is expected to begin recruiting in the next several months.