Systemic availability and metabolism of colonic‐derived short‐chain fatty acids in healthy subjects: a stable isotope study

Abstract

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.

Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes

“…Beyond the liver, the concentration of all 3 SCFAs (acetic acid > propionic acid > butyric acid) as well as isobutyric acid have been estimated to be in the micromolar range in the systemic circulation 4,21,47-50 . Furthermore, using stable isotope technology, systemic availability of colonic-administered acetate, propionate and butyrate was shown to be 36%, 9% and 2%, respectively 51 . In another study, a net uptake of the SCFAs by adipose tissue, measured as the arteriovenous difference across the tissue times the tissue could be demonstrated 50 .…”

Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

“…In a study published in 2017, 13 C labelling was used to show that colonic administered acetate, propionate and butyrate were systemically available at 36%, 9% and 2%, respectively, with conversion of acetate into butyrate (24%) by the colonic microbiota 53 . Bifidobacteria, often stimulated by specific prebiotics, do not produce butyrate, so a probable scenario is that cross feeding by other bac teria must have resulted in production of this SCFA.…”

Gut microbiota, metabolism and psychopathology: A critical review and novel perspectives

“…These GPRs are active in neuroendocrine cells in the gut and may therefore influence signaling to the brain [46]. This also seems the most plausible route via which the SCFA exert their function because the systemic concentration is very low [47]. Ongoing developments in complex metabolomics might lead to identification of more bacteria-derived metabolites in host blood and cerebrospinal fluid in the near future.…”