AUTHOR=Wang Yanan , Ni Zaizhong , Li Jinting , Shao Ying , Yong Yidan , Lv Wendi , Zhang Simeng , Fu Tingwei , Chen Anhui 

TITLE=Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice

JOURNAL=Frontiers in Nutrition

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2023.1203430

DOI=10.3389/fnut.2023.1203430

ISSN=2296-861X

ABSTRACT=<sec><title>Introduction</title><p>The polysaccharides found in <italic>Cordyceps cicadae</italic> (<italic>C. cicadae</italic>) have received increasing academic attention owing to their wide variety of therapeutic activities.</p></sec><sec><title>Methods</title><p>This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from <italic>C. cicadae</italic> (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling.</p></sec><sec><title>Results</title><p>The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the <italic>Firmicutes/Bacteroidetes</italic> ratio and increased the abundance of <italic>Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum,</italic> and significantly decreased the abundance of <italic>Helicobacter</italic> and <italic>Lactobacillus</italic> compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that <italic>Bacteroides, Odoribacter, Alloprevotella, Parabacteroides,</italic> and <italic>Mucispirillum</italic> were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels.</p></sec><sec><title>Discussion</title><p>This indicates that <italic>C. cicadae</italic> polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.</p></sec>