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.

Short chain fatty acids (SCFA), including acetate, propionate, and butyrate, are produced during bacterial fermentation of undigested carbohydrates in the human colon. In this study, we applied a stable-isotope dilution method to quantify the in vivo colonic production of SCFA in healthy humans after consumption of inulin. Twelve healthy subjects performed a test day during which a primed continuous intravenous infusion with [1-13C]acetate, [1-13C]propionate and [1-13C]butyrate (12, 1.2 and 0.6 μmol·kg−1·min−1, respectively) was applied. They consumed 15 g of inulin with a standard breakfast. Breath and blood samples were collected at regular times during the day over a 12 h period. The endogenous rate of appearance of acetate, propionate, and butyrate was 13.3 ± 4.8, 0.27 ± 0.09, and 0.28 ± 0.12 μmol·kg−1·min−1, respectively. Colonic inulin fermentation was estimated to be 137 ± 75 mmol acetate, 11 ± 9 mmol propionate, and 20 ± 17 mmol butyrate over 12 h, assuming that 40%, 10%, and 5% of colonic derived acetate, propionate, and butyrate enter the systemic circulation. In conclusion, inulin is mainly fermented into acetate and, to lesser extents, into butyrate and propionate. Stable isotope technology allows quantifying the production of the three main SCFA in vivo and proved to be a practical tool to investigate the extent and pattern of SCFA production.

Crohn's disease (CD) and ulcerative colitis (UC) are the two major phenotypes of inflammatory bowel diseases (IBD) which constitute a spectrum of chronic, debilitating diseases characterised by a relapsing inflammation of the intestinal mucosal lining. Evidence from a variety of disciplines implicates the intestinal microbiota in the pathogenesis of idiopathic IBD and their complications, including pouchitis. Many studies have reported a dysbiosis in IBD, characterised by a decrease in diversity, a decreased abundance of some dominant commensal members (such as Clostridium IV and XIVa) and an increase in detrimental bacteria (such as sulphate reducing bacteria and Escherichia coli). Therapies such as prebiotics and probiotics aim to selectively manipulate the intestinal microbiota and have been evaluated as an attractive therapeutic option with few side effects. The multispecies product VSL#3 was found effective in preventing and maintaining remission in pouchitis, whereas both VSL#3 and E. coli Nissle were effective in maintaining remission in UC. A more drastic approach to restore the composition of the microbiota and correct the underlying imbalance is a faecal microbiota transplantation (FMT). FMT has been successfully applied to treat patients with even recalcitrant Clostridium difficile infection. Particularly in UC, the majority of studies suggest that FMT may be an effective treatment option although the evidence is still limited. It is anticipated that our increasing knowledge on the composition and function of the intestinal microbiota components will allow in the future for a better selection of highly performing bacteria with specific functions required for specific benefits.

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