Highlights
- •Previous methods to measure (intestinal) SCFA production might be inaccurate.
- •We assessed SCFA production with stable tracer pulse approach and compartmental modeling.
- •SCFA production and fluxes were reduced in aging but not affected by presence of COPD.
- •Non-compartmental SCFA production measurements underestimate production in inaccessible (intestinal) pool.
Abstract
Background
Production rates of the short-chain fatty acids (SCFA) acetate, propionate, and butyrate,
which are beneficial metabolites of the intestinal microbiota, are difficult to measure
in humans due to inaccessibility of the intestine to perform measurements, and the
high first-pass metabolism of SCFAs in colonocytes and liver. We developed a stable
tracer pulse approach to estimate SCFA whole-body production (WBP) in the accessible
pool representing the systemic circulation and interstitial fluid. Compartmental modeling
of plasma enrichment data allowed us to additionally calculate SCFA kinetics and pool
sizes in the inaccessible pool likely representing the intestine with microbiota.
We also studied the effects of aging and the presence of Chronic Obstructive Pulmonary
Disease (COPD) on SCFA kinetics.
Methods
In this observational study, we designed a two-compartmental model to determine SCFA
kinetics in 31 young (20–29 y) and 71 older (55–87 y) adults, as well as in 33 clinically
stable patients with moderate to very severe COPD (mean (SD) FEV1, 46.5 (16.2)% of predicted). Participants received in the fasted state a pulse containing
stable tracers of acetate, propionate, and butyrate intravenously and blood was sampled
four times over a 30 min period. We measured tracer-tracee ratios by GC–MS and used
parameters obtained from two-exponential curve fitting to calculate non-compartmental
SCFA WBP and perform compartmental analysis. Statistics were done by ANCOVA.
Results
Acetate, propionate, and butyrate WBP and fluxes between the accessible and inaccessible
pools were lower in older than young adults (all q < 0.0001). Moreover, older participants
had lower acetate (q < 0.0001) and propionate (q = 0.019) production rates in the
inaccessible pool as well as smaller sizes of the accessible and inaccessible acetate
pools (both q < 0.0001) than young participants. WBP, compartmental SCFA kinetics,
and pool sizes did not differ between COPD patients and older adults (all q > 0.05).
Overall and independent of the group studied, calculated production rates in the inaccessible
pool were on average 7 (acetate), 11 (propionate), and 16 (butyrate) times higher
than non-compartmental WBP, and sizes of inaccessible pools were 24 (acetate), 31
(propionate), and 55 (butyrate) times higher than sizes of accessible pools (all p < 0.0001).
Conclusion
Non-compartmental production measurements of SCFAs in the accessible pool (i.e. systemic
circulation) substantially underestimate the SCFA production in the inaccessible pool,
which likely represents the intestine with microbiota, as assessed by compartmental
analysis.
Graphical abstract
Graphical Abstract
Abbreviations:
BMI (body mass index), COPD (Chronic Obstructive Pulmonary Disease), FEV1 (forced expiratory volume in 1 s), Fij (tracee flux from compartment j to compartment i [μmol·min−1]), FVC (forced vital capacity), kij (fractional tracer exchange rate from compartment j to compartment i [min−1]), Qi (tracee pool size in compartment i [μmol]), qi (tracer pool size in compartment i [μmol]), SCFA (short-chain fatty acid), TTR (tracer-tracee ratio), Ui (endogenous production in compartment i [μmol·min−1]), WBP (whole-body production [μmol·min−1]), WbRa (whole-body rate of appearance [μmol·min−1])Keywords
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Article info
Publication history
Published online: January 12, 2023
Accepted:
January 9,
2023
Received:
October 22,
2022
Identification
Copyright
© 2023 Elsevier Inc. All rights reserved.
