Higher habitual FODMAP intake is associated with lower body mass index, lower insulin resistance and higher short-chain fatty acid-producing microbiota in people with prediabetes

Aims/hypothesis The quantity and quality of FODMAPs can alter the relative abundance of gut microbiota with metabolic consequences although similar data are lacking in people with prediabetes. We investigated associations between habitual FODMAP contents, gut microbiota and glucose/insulin responses in subjects with prediabetes. Methods In this prospective cross-sectional study, ninety-eight subjects with impaired glucose tolerance (IGT) (mean age: 57±7 years, 43 % men) had assessment of body composition, 6-point oral glucose tolerance tests (OGTT), Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) and 3-day dietary intake. We analysed faecal samples in a sub-group of 20 subjects with IGT and 10 subjects with normal glucose tolerance by 16S rRNA microbiome analysis. Results Obese subjects with IGT had the lowest daily FODMAP intake compared with their non-overweight and non-obese counterparts (5.7 (3.9-7.9) vs 7.1 (5.0-11.3) vs 9.9 (4.1-22.4) g/day, p=0.024) despite having similar total daily energy intake. Total content of FODMAPs was negatively correlated with body fat. After adjustment for age and gender, total FODMAPs were negatively associated with BMI and HOMA-IR. This remained significant after adjustment for macronutrients and physical activity (p=0.032 and p=0.036 respectively). FODMAP contents were strongly associated with short-chain fatty acid (SCFA)-producing bacteria, such as Lactobacillus (p=0.011), Akkermansia muciniphila (p=0.012), and Bifidobacterium longum (p=0.010), the abundance of which were negatively correlated with 2-hr plasma glucose (r = -0.524, p =0.003). Conclusion In individuals with IGT, higher habitual FODMAP intake was associated with lower body fat and insulin resistance and increased abundance of SCFA-producing bacteria, calling for interventional studies to evaluate the effects of FODMAP intake in prediabetes. ### Competing Interest Statement Monash University financially benefits from the sales of digital applications and booklets associated with the low FODMAP diet. The authors declare that they have nothing to disclose. * BIA : bioimpedance analysis CGM : continuous glucose monitoring CKK : Cholecystokinin CP : C-peptide CSS : cumulative sum scaling DEXA : Dual energy X-ray absorptiometry FODMAP : fermentable oligosaccharides, disaccharides, monosaccharides and polyols GLP1 : glucagon-like peptide-1 GOS : Galactooligosaccharides IGT : Impaired glucose tolerance LPS : Lipopolysaccharide NGT : Normal glucose tolerance NOD : nucleotide-binding oligomerization domain-containing protein PPYR γ : Peroxisome proliferator-activated receptor-γ PYY : Peptide YY rRNA : Ribosomal ribonucleic acid SCFAs : Short-chain fatty acids