Larik GNF1*, Hamari N1*, Maurer Sost M2, van Kalkeren CAJ1, Blaak EE1, Canfora EE1
*Shared first authorship
1Department of Human Biology, Institute of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University Medical Center+, Maastricht, The Netherlands; 2Centre for Healthy Eating & Food Innovation (HEFI); Maastricht University-Campus Venlo, 5928 SZ Venlo, The Netherlands, Department of Biomedical Sciences
nouhaila.hamari@maastrichtuniversity.nl
Background: The gut microbiota ferments dietary fibres, producing short-chain fatty acids (SCFAs), which may benefit host metabolism. However, long-term supplementation of single fibres has shown inconsistent effects, likely due to individual differences in the microbial fermentation capacity and SCFA production. This study investigated whether personalized fibre mixtures (PFM), designed to enhance gut microbial SCFA production, improve insulin sensitivity.
Method: This randomized placebo-controlled parallel study included 44 individuals (body mass index (BMI) 28–40 kg/m², age 35–70) with prediabetes and/or insulin resistance. Anaerobic faecal samples were screened using an in vitro colon model (TIM-2) to identify PFM that maximize SCFA production. Participants were randomized to receive either 24g of the in vitro defined PFM (n=22) or a control fibre (galacto-oligosaccharides, n=22) for 12 weeks. The primary outcome was peripheral insulin sensitivity (hyperinsulinemic-euglycemic clamp). Secondary outcomes included substrate oxidation and energy expenditure (indirect calorimetry), body composition, blood biomarkers, and faecal and circulating microbial metabolites.
Results: No differences in peripheral insulin sensitivity (M-value) were observed between the groups. However, PFM decreased fasting plasma insulin levels (Δ -0.98 ± 2.48 vs 0.90 ± 2.96 uIU/mL, P=0.037), HOMA-IR (Δ -0.27 ± 0.65 vs Δ 0.22 ± 0.76, P=0.036), body weight (Δ -0.28 ± 2.3 vs Δ 1.37 ± 1.5 kg, P=0.014), and BMI (P=0.017) with a trend toward reduced body fat mass (P=0.073) compared to control. PFM increased plasma branched-chain fatty acid isovalerate (P=0.030) and showed a trend toward increased isobutyrate levels (P=0.055) compared to control. No differences were observed in energy expenditure, substrate oxidation, blood lipids, inflammatory markers, gut-derived hormones, and SCFAs.
Conclusion: While PFM did not improve peripheral insulin sensitivity, it modestly reduced body weight and HOMA-IR, suggesting benefits for hepatic insulin sensitivity. Personalized fibre approaches may improve metabolic health in those at risk for type 2 diabetes.