Metabolic signature of 13C-labeled wheat bran consumption related to gut fermentation in humans: a pilot study

Abstract

Purpose: The aim of this pilot study was to analyze concomitantly the kinetics of production of ¹³C-labeled gut-derived metabolites from ¹³C-labeled wheat bran in three biological matrices (breath, plasma, stools), in order to assess differential fermentation profiles among subjects.

Methods: Six healthy women consumed a controlled breakfast containing ¹³C-labeled wheat bran biscuits. H₂, CH₄ and ¹³CO₂, ¹³CH₄ 24 h-concentrations in breath were measured, respectively, by gas chromatography (GC) and GC-isotope ratio mass spectrometry (GC-IRMS). Plasma and fecal concentrations of ¹³C-short-chain fatty acids (linear SCFAs: acetate, propionate, butyrate, valerate; branched SCFAs: isobutyrate, isovalerate) were quantified using GC-combustion-IRMS. Gut microbiota composition was assessed by16S rRNA gene sequencing analysis.

Results: H₂ and CH₄ 24 h-kinetics distinguished two groups in terms of fermentation-related gas excretion: high-CH₄ producers vs low-CH₄ producers (fasting concentrations: 45.3 ± 13.6 ppm vs 6.5 ± 3.6 ppm). Expired ¹³CH₄ was enhanced and prolonged in high-CH₄ producers compared to low-CH₄ producers. The proportion of plasma and stool ¹³C-butyrate tended to be higher in low-CH₄ producers, and inversely for ¹³C-acetate. Plasma branched SCFAs revealed different kinetics of apparition compared to linear SCFAs.

Conclusion: This pilot study allowed to consider novel procedures for the development of biomarkers revealing dietary fiber-gut microbiota interactions. The non-invasive assessment of exhaled gas following ¹³C-labeled fibers ingestion enabled to decipher distinct fermentation profiles: high-CH₄ producers vs low-CH₄ producers. The isotope labeling permits a specific in vivo characterisation of the dietary fiber impact consumption on microbiota metabolite production.

Clinical trial registration: The study has been registered under the number NCT03717311 at ClinicalTrials.gov on October 24, 2018.

Keywords: 13C-labeled dietary fiber; Branched short-chain fatty acids; Gut microbiota; Methane; Short-chain fatty acids; Stable isotopes.