Multi-omics signatures in new-onset diabetes predict metabolic response to dietary inulin: findings from an observational study followed by an interventional trial

Aim: To test whether multi-omics composition of the gut microbiome and metabolome (MIME) differs across lean, obese, and newly diagnosed pre/diabetes; whether MIME patterns explain heterogeneous metabolic responses to dietary inulin; and whether baseline MIME and clinical features predict response. Method: Cross-sectional study of 49 newly diagnosed pre/diabetes (DM), 66 metabolically healthy overweight/obese (OB), and 32 lean healthy (LH) volunteers integrating clinical data, dietary intake, gut microbiome (16S rRNA), fecal volatile metabolome, and serum metabolome (NMR; LC-MS for SCFAs). Subsequently, 27 DM underwent a 3‑month inulin intervention (10 g/day). Results: MIME differed between groups; DM and LH represented opposite ends of abundance spectra, with OB closer to DM. Inulin led to overall improvement in glycemic indices with high inter-individual variability, a shift of the microbiome toward a more favorable profile, and increased serum butyric and propionic acid. Better glycemic response to inulin was associated with more favorable baseline glycemia and gut microbiota-related variables (e.g., abundance of Blautia, Eubacterium halii group, Lachnoclostridium, Ruminiclostridium, Dialister, Phascolarctobacterium), higher baseline serum asparagine and lower branched-chain amino acid derivatives, and lower fecal indole and selected VOCs. Conclusion: Obesity more strongly determines MIME patterns than glycemic status. Baseline glycemia and MIME signatures explain much of the inter-individual variability in response to inulin and could enable personalization of nutritional interventions in early diabetes.

N. Ďásková, I. Modos, M. Krbcová, M. Kuzma, H. Pelantová, J. Hradecký, M. Heczková, M. Bratová, P. Videňská, P. Šplíchalová, M. Králová, M. Heniková, J. Potočková, A. Ouřadová, R. Landberg, T. Kühn, M. Cahová, J. Gojda