Structure-function relationship of Konjac glucomannan with varying acetylation degrees in modulating gut microbiota and alleviating prediabetes.

Prediabetes, a prevalent metabolic condition characterised by elevated blood glucose levels not reaching type 2 diabetes mellitus criteria, represents a critical intervention window for diabetes prevention. Konjac glucomannan (KGM) exhibits efficacy in diabetes management, but the structure-function relationships underlying its bioactivity are poorly defined. This study investigated the impact of acetylation degree (DS) on KGM's anti-prediabetic potential. Structural characterisation revealed that acetylation and deacetylation altered DS while preserving the KGM's backbone, accompanied by changes in molecular weight and viscosity. Given the pivotal role of gut microbiota in the development of diabetes, in vitro fermentation experiments using faeces from prediabetic individuals revealed that KGM with varying DS (AcKGM) enriched Bacteroides uniformis and Bacteroides coprocola, with enrichment positively correlating with DS. Consistently, mono-culture assays demonstrated preferential utilization of highly acetylated AcKGM by both species. Prediabetic animal experiments further demonstrated that AcKGM improved glucose and lipid metabolism, suppressed inflammation, and ameliorated hepatosteatosis, in a DS-dependent manner. Notably, these effects were associated with DS-dependent enrichment of B. uniformis and upregulation of beneficial faecal metabolites, including D-pantothenic acid. Collectively, these findings establish that higher DS enhances KGM's efficacy in modulating gut microbiota and alleviating prediabetes, providing mechanistic insights for structure-guided optimisation of KGM-based therapeutics.