Obesity-related Metabolome and Gut Microbiota Profiles of Juvenile Gottingen Minipigs Long-term Intake of Fructose and Resistant Starch

Multi-compartmental metabolome and gut microbiota responses to a long-term intervention diet were investigated in a juvenile Göttingen minipig model. A high-risk (HR) diet containing 20% fructose was compared to a control low-risk (LR ) diet where a similar amount was provided as a mix of digestible and resistant starch from high amylose maize. Both diets contained high levels of fat and were fed ad libitum. Liquid chromatography mass-spectrometry (LC-MS) non-targeted metabolomics was used to explore plasma, urine, and feces samples over five months. Plasma and fecal short-chain fatty acids were quantified using LC-MS and gas chromatography, respectively. 16S rDNA sequencing was used for fecal microbiota analysis. The data was analyzed using sparse multi-block partial least squares regression. The LR diet lead to high concentrations of fecal and plasma total short-chain fatty acids, primarily acetate, and a higher relative abundance microbiota associated with acetate production such as Bacteroidetes and Ruminococcus. A higher proportion of Firmicutes was measured with the HR diet, together with a lower alpha diversity compared to the LR diet. Irrespective of diet, the ad libitum exposure was accompanied by well-known biomarkers associated with obesity and diabetes, particularly branched chain amino acids, keto acids, and other catabolism metabolites.