Title:Integrated 16S rRNA Sequencing and Untargeted Metabolomics Analysis to Reveal
the Protective Mechanisms of Polygonatum sibiricum Polysaccharide on Type 2 Diabetes
Mellitus Model Rats
Volume: 24
Issue: 4
Author(s): Hui Zhang, Hanzhou Li, Baochao Pan, Shufang Zhang, Xiuhai Su, Wenjuan Sun, Tianyu Zhang, Zhaiyi Zhang, Shuquan Lv*Huantian Cui*
Affiliation:
- Department of Endocrinology and Metabolism, Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine
of Hebei Province Affiliated to Hebei University of Chinese Medicine, Cangzhou, China
- Faculty of Life Sciences, Shandong University, Shandong, China
Keywords:
Type 2 diabetes mellitus, Polygonatum sibiricum polysaccharide, gut microbiota, arginine and proline metabolism, tryptophan metabolism, glutathione metabolism.
Abstract:
Background: Polygonatum sibiricum polysaccharide (PSP) can improve insulin resistance and inhibit
oxidative stress. However, the detailed anti-diabetic mechanism of PSP is still poorly defined.
Methods: In this study, the anti-diabetic, anti-inflammatory and anti-oxidative effects of PSP were evaluated on a
type 2 diabetes mellitus (T2DM) rat model. Furthermore, we investigated the changes in gut microbiota and serum
metabolites in T2DM rats after PSP treatment through 16S rRNA sequencing and untargeted metabolomics analyses.
Results: Our results showed that PSP exhibited significant anti-diabetic, anti-inflammatory and anti-oxidative effects
on T2DM model rats. In addition, 16S rRNA sequencing showed that PSP treatment decreased the Firmicutes/
Bacteroidetes ratio in the gut. At the genus level, PSP treatment increased the relative abundances of Blautia,
Adlercreutzia, Akkermansia and Parabacteroides while decreasing Prevotella, Megamonas funiformis and Escherichia.
Untargeted metabolomics analysis revealed that PSP treatment could affect 20 metabolites, including hexanoylglycine,
(±)5(6)-DiHET, ecgonine, L-cysteine-S-sulfate, epitestosterone, (±)12(13)-DiHOME, glutathione, L-ornithine, Dmannose
6-phosphate, L-fucose, L-tryptophan, L-kynurenine, serotonin, melatonin, 3-hydroxyanthranilic acid, xylitol,
UDP-D-glucuronate, hydroxyproline, 4-guanidinobutyric acid, D-proline in T2DM model rats, these metabolites are
associated with arginine and proline metabolism, tryptophan metabolism, amino sugar and nucleotide sugar metabolism,
pentose and glucuronate interconversions, glutathione metabolism, arginine biosynthesis, ascorbate and aldarate
metabolism pathways. Spearman correlation analysis results showed that the modulatory effects of PSP on the arginine
and proline metabolism, tryptophan metabolism, and glutathione metabolism pathways were related to the regulation
of Prevotella, Megamonas funiformis, Escherichia, Blautia and Adlercreutzia.
Conclusion: Our research revealed the therapeutic, anti-inflammatory and anti-oxidative effects of PSP on T2DM.
The mechanisms of PSP on T2DM are associated with improving the dysbiosis of gut microbiota and regulating
arginine and proline metabolism, tryptophan metabolism, and glutathione metabolism in serum.