Physicochemical properties and molecular weight-dependent gut microbiota modulation of inulin-type fructans from Codonopsis bulleynana

The therapeutic efficacy of dietary fibers is closely related to structural heterogeneity, yet the impact of chain length on physicochemical behavior and gut microbiota modulation remains unclear. Herein, three homologous linear β-(2 → 1)-linked inulin-type fructans with distinct molecular weights, hereafter referred to as CBP1–3, were isolated from Codonopsis bulleynana . All fractions spontaneously assembled into stable supramolecular nanoparticles/disks in water, a process thermodynamically driven by intermolecular hydrogen bonding according to molecular dynamics simulations. Biological evaluation revealed a striking divergence: while low-molecular-weight fractions showed superior efficacy in in vitro fermentation, the relatively high-molecular-weight CBP1 exhibited superior in vivo potency. Multi-omics analysis supports the hypothesis that this supramolecular structure, in synergy with extended chain length, may function as a structural barrier and confer sustained-release characteristics. This likely limits mucin-degrading Akkermansia proliferation via a nutrient-sparing effect, thereby maintaining metabolic homeostasis. These findings demonstrate that relatively high-molecular-weight polysaccharides possess unique ecological advantages in physiological contexts, challenging traditional in vitro screening paradigms and positioning CBP1 as a promising candidate for precision microbiome restoration.