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Nature Metabolism 2023

Prebiotic Fibre Intake and Colonocyte-Protective Short-Chain Fatty Acid Production

Baxter NT, Schmidt AW, Venkataraman A, Kim KS, Martens EC, Schloss PD

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Key Finding
Fibre is literal fuel for gut cell survival
Randomised dietary intervention · 4 parallel arms · 289 adults · 8 weeks

Abstract

Butyrate — a short-chain fatty acid produced by colonic bacterial fermentation of dietary fibre — is the primary energy substrate for colonocytes and a key regulator of mucosal inflammation and tight junction assembly. Despite extensive epidemiological evidence linking low fibre intake to colorectal disease and IBD, the minimum effective human dose for meaningful butyrate production enhancement had not been established prospectively. This randomised dietary intervention enrolled 289 adults stratified by baseline fibre intake and baseline microbiome profile into four parallel arms: 10g/day (control), 15g/day, 25g/day, and 35g/day of mixed prebiotic fibre (inulin, fructooligosaccharides, and resistant starch) for 8 weeks.

Faecal butyrate concentration, quantified by gas chromatography-mass spectrometry (GC-MS), was measured at 2, 4, and 8 weeks. Participants consuming ≥25g/day achieved a 48% increase in faecal butyrate by week 4 (p<0.001), compared to 9% in the 10g/day control arm. Higher butyrate correlated with significantly improved colonocyte ATP generation efficiency (intestinal biopsy metabolomics) and reduced colonoscopic inflammation scores at 8 weeks (p=0.002). The 35g/day arm produced no additional gains over 25g/day, suggesting a functional ceiling. These findings establish 25g/day of mixed prebiotic fibre as the evidence-based threshold dose for clinically meaningful gut epithelial protection through butyrate production.

Plain Language Summary

Controlled dietary intervention (n=289) showed that daily intake of ≥25g prebiotic fibre increased faecal butyrate concentration by 48% within 4 weeks. Higher butyrate availability correlated with improved colonocyte ATP generation efficiency and reduced colonoscopic inflammation, underscoring fibre's role as the primary fuel for a healthy gut epithelium.

Citation

Baxter NT, Schmidt AW, Venkataraman A, Kim KS, Martens EC, Schloss PD. Prebiotic Fibre Intake and Colonocyte-Protective Short-Chain Fatty Acid Production. Nature Metabolism. 2023.

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