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Characterization of diet-dependent temporal changes in circulating short-chain fatty acid concentrations: A randomized crossover dietary trial

Brignardello, J., Fountana, S., Posma, J.M., Chambers, E.S., Nicholson, J.K., Wist, J., Frost, G., Garcia-Perez, I. and Holmes, E. (2022) Characterization of diet-dependent temporal changes in circulating short-chain fatty acid concentrations: A randomized crossover dietary trial. The American Journal of Clinical Nutrition .

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Production of SCFAs from food is a complex and dynamic saccharolytic fermentation process mediated by both human and gut microbial factors. Knowledge of SCFA production and of the relation between SCFA profiles and dietary patterns is lacking.


Temporal changes in SCFA concentrations in response to 2 contrasting diets were investigated using a novel GC-MS method.


Samples were obtained from a randomized, controlled, crossover trial designed to characterize the metabolic response to 4 diets. Participants (n = 19) undertook these diets during an inpatient stay (of 72 h). Serum samples were collected 2 h after breakfast (AB), after lunch (AL), and after dinner (AD) on day 3, and a fasting sample (FA) was obtained on day 4. The 24-h urine samples were collected on day 3. In this substudy, samples from the 2 extreme diets representing a diet with high adherence to WHO healthy eating recommendations and a typical Western diet were analyzed using a bespoke GC-MS method developed to detect and quantify 10 SCFAs and precursors in serum and urine samples.


Considerable interindividual variation in serum SCFA concentrations was observed across all time points, and temporal fluctuations were observed for both diets. Although the sample collection timing exerted a greater magnitude of effect on circulating SCFA concentrations, the unhealthy diet was associated with a lower concentration of acetic acid (FA: coefficient: –17.0; SE: 5.8; P-trend = 0.00615), 2-methylbutyric acid (AL: coefficient: –0.1; SE: 0.028; P-trend = 4.13 × 10–4 and AD: coefficient: –0.1; SE: 0.028; P-trend = 2.28 × 10–3), and 2-hydroxybutyric acid (FA: coefficient: –15.8; SE: 5.11; P-trend: 4.09 × 10–3). In contrast, lactic acid was significantly higher in the unhealthy diet (AL: coefficient: 750.2; SE: 315.2; P-trend = 0.024 and AD: coefficient: 1219.3; SE: 322.6; P-trend: 8.28 × 10–4).


The GC-MS method allowed robust mapping of diurnal patterns in SCFA concentrations, which were affected by diet, and highlighted the importance of standardizing the timing of SCFA measurements in dietary studies. This trial was registered on the NIHR UK clinical trial gateway and with ISRCTN as ISRCTN43087333.

Item Type: Journal Article
Murdoch Affiliation(s): Australian National Phenome Centre
Publisher: Oxford University Press
Copyright: © 2022 The Authors.
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