Short-term high fat diet-induced metabolic endotoxemia in older individuals with obesity: a randomized crossover study.

BACKGROUND: Lipopolysaccharide, also known as endotoxin, in Gram-negative bacteria is associated with obesity and a high fat (HF) diet. OBJECTIVES: 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. METHODS: 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. RESULTS: Participants were 64 y old (95% confidence interval [95% CI]: 62, 66), and 66% were female. Body mass index (BMI; kg/m(2)) was 24.3 kg/m(2) (95% CI: 23.5, 25.0) and 36.6 kg/m(2) (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. CONCLUSIONS: 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.