Hyaluronan exerts unique microbiome and metabolic effects compared with pectin: a multi-omics study of dietary polysaccharides.

Dietary polysaccharides are increasingly recognized as modulators of host metabolism through intestinal interactions, yet not all exert comparable systemic effects. In this context, dietary hyaluronan (HA) is distinguished by its clinical efficacy on connective tissues. We investigated whether oral HA modulates the small-intestinal microbiome, systemic metabolome, and lipid metabolism, and compared its effects with pectin. Using a healthy murine model, we combined 16S rRNA sequencing, metabolomics, lipidomics, and correlation analyses. Oral HA triggered profound and previously undescribed shifts in the small-intestinal microbiome, while pectin's effects were markedly weaker. Both supplements increased microbial diversity, with HA specifically enriching taxa such as Turicibacter, Clostridium, and Lachnoclostridium. HA was also associated with elevated systemic metabolites, enhancing redox status. Hydroxybutyrate and related metabolites increased, consistent with enhanced lipolysis. HA was linked to reduced glycogen degradation without effects on synthesis, whereas pectin was related to lowered glycogen synthesis without alterations in degradation. Notably, HA was associated with modulated plasma and hepatic lipid metabolism. Specifically, lipid mediators playing roles in organismal homeostasis, inflammation, and pain modulation were altered. Collectively, these findings indicate that oral HA exerts a unique effect on the intestinal microbiome, systemic metabolome, and lipidome compared to pectin.