Auricularia auricula‐judae (Bull.) polysaccharides improve type 2 diabetes in HFD/STZ‐induced mice by regulating the AKT/AMPK signaling pathways and the gut microbiota

Abstract

Auricularia auricula‐judae is an edible fungus with high nutritional value due to abundant polysaccharides, and is acknowledged as traditional food and medicine in Asia. Polysaccharides from A. auricula (AAPs) are typically fungal polysaccharides and have a wide range of biological activities. It has been shown the potential of AAPs to improve diabetes as an effective adjuvant, but the underlying mechanism remains unclear. In this study, we explored the effects and potential mechanism of AAPs on type 2 diabetes (T2D) using a high‐fat diet and streptozotocin (STZ) induced C57BL/6J mice. The results indicated that 50 and 100 mg/kg AAPs significantly decreased inflammation, liver injury, and insulin resistance. In addition, AAPs improved glycolipid metabolism disorders by activating the AKT and adenosine 5`monophosphate‐activated protein kinase (AMPK) signaling pathways in T2D mice. Furthermore, we investigated the association between changes of gut microbiota and AAPs effects using high‐throughput sequencing of 16S rDNA for fecal samples. In our study, AAPs elevated gut microbiota diversity and optimized microbial composition and function in T2D mice, characterized by increased Lactobacillus and Bacteroides abundance and decreased Clostridium and Allobaculum abundance. Particularly, AAPs intervention mainly affected the amino acid metabolism and glycolipid metabolism pathways. Overall, this study confirms that AAPs can improve type 2 diabetes by regulating the AKT and AMPK pathways and modulating intestinal microbiota. Practical Application The article systematically verified the positive effects of AAPs on insulin resistance, glycolipid metabolism disorder, inflammation, and liver injury, key factors closely related to T2D. Furthermore, our study firstly determined the specific underlying mechanism that AAPs ameliorates T2D through regulating AKT/AMPK pathways and modifying the gut microbiota. These results could offer a full explanation and a potential option for the adjuvant therapy of diabetes with AAPs.

Fermented noni (Morinda citrifolia L.) fruit juice improved oxidative stress and insulin resistance under the synergistic effect of Nrf2/ARE pathway and gut flora in db/db mice and HepG2 cells

“…76 FNJ supplementation decreased the F/B ratio, which was consistent with other dietary modifiers. 2,24 Moreover, FNJ administration significantly raised certain beneficial bacteria genera in db/db mice such as Odoribacter, Rikenella, Muribaculum, and Anaerostipes, and mitigated pernicious bacteria Enterorhabdus. 2,23 Meanwhile, FNJ also increased the relative abundance of Alistipes, Colidextribacter, Mucispirillum, and Butyricicoccus and alleviated Limosilactobacillus, Ligilactobacillus, Candidatus-Arthromitus, [Eubacterium]-ventriosum-group, and Staphylococcus at the genus level.…”

“…2,24 Moreover, FNJ administration significantly raised certain beneficial bacteria genera in db/db mice such as Odoribacter, Rikenella, Muribaculum, and Anaerostipes, and mitigated pernicious bacteria Enterorhabdus. 2,23 Meanwhile, FNJ also increased the relative abundance of Alistipes, Colidextribacter, Mucispirillum, and Butyricicoccus and alleviated Limosilactobacillus, Ligilactobacillus, Candidatus-Arthromitus, [Eubacterium]-ventriosum-group, and Staphylococcus at the genus level. LDA analysis proved that T2DM mice enriched in harmful bacteria Enterobacteriaceae, Klebsiella, and Klebsiella-pneumonia, while FNJ significantly upregulated Rikenellaceae.…”

“…49,50 The microbiome features (genus) with oxidative stress and IR traits (MDA, SOD, CAT, GPx, FBG, OGTT, ITT, HbA1c, serum insulin, HOMA-IR, ISI, hepatic glycogen, and the Nrf2/ARE pathway) were correlated by the non-parametric Spearman correlation test. 2…”

“…It is accompanied by hyperglycemia and hyperinsulinemia at the early stage and mainly characterized by insulin resistance (IR) and relative insulin secretion defect owing to impaired insulin signal transduction. 1,2 Insulin maintains blood glucose homeostasis by stimulating miscellaneous physiological reactions of peripheral tissues such as liver, fat, and skeletal muscle. However, when IR occurs, it will cause severe diabetic complications such as cardiovascular disease and diabetic nephropathy and become a key link in the occurrence and development of T2DM.…”

Effects of Auricularia auricula Polysaccharides on Gut Microbiota and Metabolic Phenotype in Mice

“…Many studies have shown that dietary polysaccharides with different structures could regulate the composition of intestinal flora precisely [ 13 , 14 ]. Xu et al found that Auricularia auricula polysaccharides (AAP) elevated intestinal flora diversity and optimized microbial composition and function in T2D mice, characterized by increased Lactobacillus and Bacteroides and decreased Clostridium and Allobaculum [ 15 ]; however, there are few studies on the regulatory effects of AAP on gut microbiota in normal mice, especially concerning AAP from the Qinba Mountains.…”