Structural analysis of polysaccharide from Inonotus obliquus and investigate combined impact on the sex hormones, intestinal microbiota and metabolism in SPF male mice

The dysregulation of sex hormone levels is associated with metabolic disorders such as obesity. Inonotus obliquus polysaccharide (IOP) exhibits a promising therapeutic effect on conditions like obesity and diabetes, potentially linked to its influence on intestinal microbiota and metabolism. The exact cause and mechanisms that link sex hormones, gut microbiota and metabolism are still unknown. In this research, we examined the molecular weight, monosaccharide composition, and glycosidic bond type of IOP. We found that IOP mostly consists of alpha-structured 6‑carbon glucopyranose, with a predominant (1 → 4) linkage to monosaccharides and a uniform distribution. Following this, we administered two different concentrations of IOP to mice through gavage. The results of the enzyme-linked immunosorbent assay (ELISA) demonstrated a significant increase in testosterone (T) levels in the IOP group as compared to the control group. Additionally, the results of tissue immunofluorescence indicated that increased IOP led to a decrease in adiponectin content and an increase in SET protein expression. The study also revealed changes in the intestinal microbiota and metabolic changes in mice through 16S rRNA data and non-targeted LC-MS data, respectively. The study also found that IOP mainly affects pathways linked to glycerophospholipid metabolism. In addition, it has been observed that there is an increase in the number of beneficial bacteria, such as the Eubacterium coprostanoligenes group and g.Lachnospiraceae NK4A136 group, while the levels of metabolites that are linked to obesity or diabetes, such as 1,5-anhydrosorbitol, are reduced. Furthermore, biomarker screening has revealed that the main microorganism responsible for the differences between the three groups is g.Erysipelatoclostridiaceae. In summary, these findings suggest that IOP exerts its therapeutic effects through a synergistic interplay between sex hormones, gut microbiome composition, and metabolic processes.