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Randomized Controlled Trial
.2017 Jan 15;595(2):541-555.
doi: 10.1113/JP272613. Epub 2016 Sep 18.

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

Affiliations
Randomized Controlled Trial

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

Eef Boets et al. J Physiol..

Abstract

Key points: The short-chain fatty acids (SCFAs) are bacterial metabolites produced during the colonic fermentation of undigested carbohydrates, such as dietary fibre and prebiotics, and can mediate the interaction between the diet, the microbiota and the host. We quantified the fraction of colonic administered SCFAs that could be recovered in the systemic circulation, the fraction that was excreted via the breath and urine, and the fraction that was used as a precursor for glucose, cholesterol and fatty acids. This information is essential for understanding the molecular mechanisms by which SCFAs beneficially affect physiological functions such as glucose and lipid metabolism and immune function.

Abstract: The short-chain fatty acids (SCFAs), acetate, propionate and butyrate, are bacterial metabolites that mediate the interaction between the diet, the microbiota and the host. In the present study, the systemic availability of SCFAs and their incorporation into biologically relevant molecules was quantified. Known amounts of13 C-labelled acetate, propionate and butyrate were introduced in the colon of 12 healthy subjects using colon delivery capsules and plasma levels of13 C-SCFAs13 C-glucose,13 C-cholesterol and13 C-fatty acids were measured. The butyrate-producing capacity of the intestinal microbiota was also quantified. 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 to13 CO2 , whereas less than 0.05% of the SCFAs were excreted into urine. These results will allow future evaluation and quantification of SCFA production from13 C-labelled fibres in the human colon by measurement of13 C-labelled SCFA concentrations in blood.

Keywords: colonic fermentation; metabolism; short-chain fatty acids; stable isotopes; systemic exposure.

© 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

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Figures

Figure 1
Figure 1.In vitro andin vivo evaluation of the performance of the colon delivery capsules
A,in vitro dissolution profile of colon delivery capsules at different pH (n = 2).B,14CO2 and13CO2 appearance in breath after administration of13C‐acetate,13C‐propionate and13C‐butyrate colon delivery capsules in 12 subjects. The simultaneous rise in the breath of14CO2 and13CO2 indicates a correct delivery of13C‐acetate in the colon.C, comparison of the time of release of the13C‐SCFAs from the capsules (indicated by the time point at which 20% of the cumulative amount recovered was obtained, t20%) and arrival of the test meal in the colon (indicated by the orocecal transit time, OCTT);n = 36, except for OCTT (n = 30). Results are expressed as the mean ± SD.
Figure 2
Figure 2. Calculation of the systemic availability of colonic‐administered13C‐SCFAs
A, Typical graph depicting13C‐acetate concentrations in plasmavs. time.B, systemic availability results of acetate, propionate and butyrate for all 12 subjects. Results are expressed as the mean ± SD.
Figure 3
Figure 3. Cross‐feeding of SCFAs
A, overview and quantitative indication of the interconversions between acetate, propionate and butyrate (n = 12).B, appearance of13C‐acetate in plasma after administration of a coated and uncoated capsule filled with13C‐acetate. Without coating,13C‐acetate was released in the proximal intestine and appears at an earlier time in plasma compared to a coated capsule.C, appearance of13C‐butyrate in plasma after administration of a coated and uncoated capsule filled with13C‐acetate.13C‐butyrate is only formed when13C‐acetate is properly released in the colon.
Figure 4
Figure 4. Butyrate‐producing capacity
A, gene copy numbers of butyrate‐producing colon bacteria and butyrate‐producing colon enzymes in faecal samples (n = 11).BC, correlation between acetate into butyrate conversion and enzymes involved in butyrate synthesis (n = 11).DE, correlation between acetate into butyrate conversion and the most abundant butyrate‐producing bacteria (n = 11).
Figure 5
Figure 5. Assimilation of13C‐SCFAs in biologically relevant molecules
A, typical example that shows the appearance of13C‐propionate followed by13C‐glucose in plasma after colonic administration of13C‐propionate.B, fraction of administered13C‐propionate recovered in glucose (n = 12).C, typical example that shows the appearance of13C‐acetate followed by13C‐palmitate,13C‐stearate and13C‐oleate in plasma after colonic administration of13C‐acetate.D, fraction of administered13C‐acetate recovered in palmitate (C16), stearate (C18) and oleate (C18:1) (n = 12).E, typical examples that show the appearance of13C‐acetate and13C‐propionate followed by13C‐cholesterol in plasma after colonic administration of13C‐acetate and13C‐propionate.F, fraction of administered13C‐acetate and13C‐propionate recovered in cholesterol (n = 12). Results are expressed as the mean ± SD.
Figure 6
Figure 6. Recovery of13C‐acetate,13C‐propionate and13C‐butyrate in the breath as13CO2
Results are expressed as the mean ± SD (n = 12).
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