Ogilvie Anna R, Onishi Janet C, Schlussel Yvette, Kumar Anil, Häggblom Max M, Kerkhof Lee J, Shapses Sue A
Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, United States.
Department of Biochemistry and Microbiology, Rutgers University, New Brunswick, NJ, United States.
Am J Clin Nutr. 2025 Aug;122(2):601-611. doi: 10.1016/j.ajcnut.2025.06.001. Epub 2025 Jun 4.
Lipopolysaccharide, also known as endotoxin, in Gram-negative bacteria is associated with obesity and a high fat (HF) diet.
The objective of this study was to determine whether short-term HF diet compared with low fat (LF) intake affects serum endotoxin and gut microbiota in a controlled trial of older individuals with obesity or normal weight.
In this randomized crossover study, adults (50-79 y old) with obesity or normal weight were assigned to 5 d of HF (40%) diet or LF (20%) diet followed by a washout period and then the other diet. A 5-h mixed meal tolerance test (46% fat) was performed after the LF diet. Serum was analyzed for endotoxin, zonulin, and inflammatory biomarkers. Fecal bacterial community was analyzed by rRNA operon profiling.
Participants were 64 y old (95% confidence interval [95% CI]: 62, 66), and 66% were female. Body mass index (BMI; kg/m) was 24.3 kg/m (95% CI: 23.5, 25.0) and 36.6 kg/m (95% CI: 33.4, 39.8) in the group with normal body weight (n = 16) and obesity (n = 16), respectively. The rise in postprandial endotoxin was 1.8-fold higher in individuals with obesity compared with normal weight (P = 0.010). After the study diets, fasting serum endotoxin was higher after the HF diet than the LF diet in the group with obesity (mean difference: 0.13 endotoxin unit [EU]/mL [95% CI: 0.02, 0.24], P = 0.022) but not in the normal weight group (mean difference: 0.03 EU/mL [95% CI: -0.07, 0.14], P = 0.613). Serum zonulin concentrations were higher after the HF diet than the LF diet (P < 0.001) and in the group with obesity compared with normal weight (P < 0.001). Fecal community analysis indicated minimal changes in Gram-negative bacteria due to diet or BMI groups.
Serum endotoxin concentrations in individuals with obesity increase following a HF diet or a meal, and these data suggest that it is explained by intestinal permeability rather than a shift in the gut microbiome. This trial was registered at https://clinicaltrials.gov/study/NCT05327868.
革兰氏阴性菌中的脂多糖，也称为内毒素，与肥胖和高脂（HF）饮食有关。
本研究的目的是在一项针对肥胖或体重正常的老年人的对照试验中，确定短期高脂饮食与低脂（LF）摄入相比是否会影响血清内毒素和肠道微生物群。
在这项随机交叉研究中，将肥胖或体重正常的成年人（50 - 79岁）分配到5天的高脂（40%）饮食或低脂（20%）饮食组，随后是洗脱期，然后再接受另一种饮食。在低脂饮食后进行5小时混合餐耐量试验（脂肪含量46%）。分析血清中的内毒素、闭合蛋白和炎症生物标志物。通过rRNA操纵子分析粪便细菌群落。
参与者年龄为64岁（95%置信区间[95%CI]：62，66），66%为女性。体重正常组（n = 16）和肥胖组（n = 16）的体重指数（BMI；kg/m²）分别为24.3 kg/m²（95%CI：23.5，25.0）和36.6 kg/m²（95%CI：33.4，39.8）。与体重正常者相比，肥胖个体餐后内毒素升高幅度高1.8倍（P = 0.010）。在研究饮食后，肥胖组高脂饮食后空腹血清内毒素高于低脂饮食（平均差异：0.13内毒素单位[EU]/mL[95%CI：0.02，0.24]，P = 0.022），但体重正常组无差异（平均差异：0.03 EU/mL[95%CI： - 0.07，0.14]，P = 0.613）。高脂饮食后血清闭合蛋白浓度高于低脂饮食（P < 0.001），且肥胖组高于体重正常组（P < 0.001）。粪便群落分析表明，饮食或BMI组对革兰氏阴性菌的影响极小。
肥胖个体在高脂饮食或进食后血清内毒素浓度会升高，这些数据表明这是由肠道通透性而非肠道微生物群的变化所解释。该试验已在https://clinicaltrials.gov/study/NCT05327868注册。
