An inulin from Asparagus cochinchinensis relieves slow transit constipation associated with Akkermansia muciniphila enrichment, kynurenic acid restoration, and NLRP3 attenuation.

Slow transit constipation (STC) involves impaired colonic motility, and effective therapies remain limited. Inulin-type fructans (ITFs) are prebiotic polysaccharides linked to intestinal function, but mixtures with broad chain-length distributions hinder structure-function interpretation. In this study, we adopted a degree of polymerization (DP)-anchored strategy to compare two structurally related ITFs from Asparagus cochinchinensis: ACO (DP = 6) and ACNP (DP = 15). In a loperamide (LOP)-induced STC model, ACNP, but not ACO, improved fecal output and water content, shortened the time to first black stool, and enhanced intestinal transit. ACNP alleviated colonic injury, restored mucus-associated protection, improved epithelial barrier integrity, and preserved enteric neurons and nerve-fiber networks. Multi-omics analyses showed that ACNP treatment was associated with enrichment of Akkermansia muciniphila (AKK), restoration of kynurenic acid (KYNA), reduced proinflammatory mediators, and attenuated NLRP3 inflammasome activation. Antibiotic depletion largely abolished these benefits, whereas fecal microbiota transplantation (FMT) restored them. Moreover, live AKK supplementation and exogenous KYNA reproduced key protective effects and were associated with reduced NLRP3 inflammasome activation. Overall, this DP-anchored comparison identified ACNP as the more effective fructan fraction and supports a microbiota-dependent protective response involving AKK enrichment, KYNA restoration, NLRP3 inflammasome attenuation, barrier protection, and enteric nervous system (ENS) preservation.