SUMMARY BackgroundButyrate, a short-chain fatty acid, is a main end-product of intestinal microbial fermentation of mainly dietary fibre. Butyrate is an important energy source for intestinal epithelial cells and plays a role in the maintenance of colonic homeostasis.

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Boets, E. et al. (2017) Systemic availability and metabolism of colonicderived short-chain fatty acids in healthy subjects: a stable isotope study. Journal of Physiology, 595(2), pp. 541-555. (doi:10.1113/JP272613) This is the author's final accepted version.There may be differences between this version and the published version. You are advised to consult the publisher's version if you wish to cite from it.http://eprints.gla.ac.uk/128777/ Key Point Summary SCFAs are bacterial metabolites produced during colonic fermentation of undigested carbohydrates, such as dietary fibre and prebiotics, and could mediate the interaction between diet, the microbiota and the host. We quantified the fraction of colonic administered SCFA that could be recovered in the systemic circulation, the fraction that was excreted via breath and urine and the fraction that was used as a precursor for glucose, cholesterol and fatty acids. This information is essential to understand the molecular mechanisms by which SCFA beneficially affect physiological functions such as glucose and lipid metabolism and immune function. AbstractThe short-chain fatty acids (SCFAs), acetate, propionate and butyrate are bacterial metabolites that mediate the interaction between diet, the microbiota and the host. In this study, the systemic availability of SCFAs and their incorporation into biologically relevant molecules was quantified. Known amounts of 13 C-labelled acetate, propionate and butyrate were introduced in the colon of 12 healthy subjects using colon delivery capsules and plasma levels of 13 C-SCFAs and of 13 C-glucose, 13 C-cholesterol and 13 C-fatty acids were measured.The butyrate producing capacity of the intestinal microbiota was quantified as well. Systemic availability of colonic-administered acetate, propionate and butyrate was 36%, 9% and 2%, respectively. Conversion of acetate into butyrate (24%) was the most prevalent interconversion by the colonic microbiota and was not related to the butyrate-producing capacity in the faecal samples. Less than 1% of administered acetate was incorporated into cholesterol and <15% in fatty acids. On average, 6% of colonic propionate was incorporated into glucose. The SCFAs were mainly excreted via the lungs after oxidation to 13 CO 2 whereas less than 0.05% of the SCFAs were excreted into urine. These results will allow future evaluation and quantification of SCFAs production from 13 C-labelled fibres in the human colon by measuring 13 C-labelled SCFA concentrations in blood.

Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.