The metabolome and gut microbiota were investigated in a juvenile Göttingen minipig model. This study aimed to explore the metabolic effects of two carbohydrate sources with different degrees of risk in obesity development when associated with a high fat intake. A high-risk (HR) high-fat diet containing 20% fructose was compared to a control lower-risk (LR) high-fat diet where a similar amount of carbohydrate was provided as a mix of digestible and resistant starch from high amylose maize. Both diets were fed ad libitum. Non-targeted metabolomics was used to explore plasma, urine, and feces samples over five months. Plasma and fecal short-chain fatty acids were targeted and quantified. Fecal microbiota was analyzed using genomic sequencing. Data analysis was performed using sparse multi-block partial least squares regression. The LR diet increased concentrations of fecal and plasma total short-chain fatty acids, primarily acetate, and there was a higher relative abundance of 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 to the high-energy diets was accompanied by well-known biomarkers associated with obesity and diabetes, particularly branched-chain amino acids, keto acids, and other catabolism metabolites.

A major challenge in affluent societies is the increase in disorders related to gut and metabolic health. Chronic over nutrition by unhealthy foods high in energy, fat, and sugar, and low in dietary fibre is a key environmental factor responsible for this development, which may cause local and systemic inflammation. A low intake of dietary fibre is a limiting factor for maintaining a viable and diverse microbiota and production of short-chain fatty acids in the gut. A suppressed production of butyrate is crucial, as this short-chain fatty acid (SCFA) can play a key role not only in colonic health and function but also at the systemic level. At both sites, the mode of action is through mediation of signalling pathways involving nuclear NF-κB and inhibition of histone deacetylase. The intake and composition of dietary fibre modulate production of butyrate in the large intestine. While butyrate production is easily adjustable it is more variable how it influences gut barrier function and inflammatory markers in the gut and periphery. The effect of butyrate seems generally to be more consistent and positive on inflammatory markers related to the gut than on inflammatory markers in the peripheral tissue. This discrepancy may be explained by differences in butyrate concentrations in the gut compared with the much lower concentration at more remote sites.