Lipid- and Glucose-lowering Effects of Rhamnan Sulphate from with Altered Gut Microbiota in Mice

Rhamnan sulphate (RS) is a sulphated polysaccharide found in green algae such as that exhibits various biological functions, including anticoagulant, antitumour, antiviral, and anti-obesity properties. In our previous clinical trial, we demonstrated that RS intake improves constipation. However, no specific bacteria showed a significant ( < .05) change. Notably, these results were obtained after a short RS inoculation period of only 2 weeks. In the present study, to evaluate the long-term effects of RS on the gut microbiota, we orally administered RS to BALB/c mice for 11 weeks, analyzed their blood biochemical data, and performed 16s rRNA-sequencing. Oral administration of RS increased body weight with increased food intake, whereas plasma total cholesterol and fasting plasma glucose levels decreased. RS-fed mice showed lower fasting insulin levels ( < .1) and decreased homeostatic model assessment for insulin resistance (HOMA-IR,  < .0001), suggesting that RS improved insulin resistance. In the feces of mice, the amounts of acetic and propionic acids increased. In the gut microbiota, predictive metagenomic profiling using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2) revealed functional alterations in Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways in RS-fed mice. Corresponding to the blood glucose-lowering effect, the glycolysis and tricarboxylic acid (TCA) cycle pathways were activated. In addition, the Firmicutes/Bacteroides (F/B) ratio, which may be associated with various health outcomes, was also reduced. These results suggest that the blood glucose-lowering effect, improvement in insulin resistance, and lipid-lowering effect of RS may be due to changes in the intestinal microbiota.