The potential mechanism of Liu–Wei–Di–Huang Pills in treatment of type 2 diabetic mellitus: from gut microbiota to short-chain fatty acids metabolism

Jul 20, 2022Acta diabetologica

How Liu-Wei-Di-Huang Pills may help treat type 2 diabetes by affecting gut bacteria and their production of short-chain fatty acids

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Abstract

Liu-Wei-Di-Huang Pills (LWDH) significantly altered gut microbiota and increased short-chain fatty acids (SCFAs) in Goto-Kakizaki rats with type 2 diabetes mellitus.

Treatment with LWDH changed the microbial structure, enhancing the presence of Firmicutes bacteria such as Lactobacillus, Allobaculum, and Ruminococcus_2.
LWDH administration led to increased levels of SCFAs, including acetic acid, propionic acid, and butyric acid.
The treatment was associated with improvements in type 2 diabetes symptoms and jejunum damage.
Potential mechanisms for these effects may involve the SCFAs-GPR43/41-GLP-1 pathway.

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BACKGROUND: Type 2 diabetes mellitus (T2DM) has already become a global pandemic. Recently, reports showed its pathogenesis was closely related to a disorder of gut microbiota. In China, the Liu-Wei-Di-Huang Pills (LWDH) have treated T2DM for thousands of years. However, its therapeutic mechanism associated with gut microbiota is worthy of further study.

AIMS: This study aims to investigate the effects of LWDH on T2DM by regulating gut microbiota and short-chain fatty acids (SCFAs) in Goto-Kakizaki (GK) rats.

METHODS: T2DM models were successfully established based on GK rats and administrated with LWDH. The changes in fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and serum insulin (INS) were determined, and the immunohistochemical (IHC) method was used to test INS expression in pancreas. The 16S-ribosomal DNA (16S rDNA) sequencing analysis assessed gut microbiota structural changes; a gas chromatography-mass spectrometer (GC-MS)-based metabolomics method was adopted to detect SCFA levels. The pathological morphology of jejunum was detected by hematoxylin-eosin (H&E) staining, and the expression of GPR43, GPR41, GLP-1, and GLP-1R was evaluated by qRT-PCR and ELISA, respectively.

RESULTS: We observed that GK rats treated with LWDH: (a) has altered the microbial structure and promoted the abundance of bacteria in Firmicutes, including Lactobacillus, Allobaculum, and Ruminococcus_2, (b) increased SCFAs levels involving acetic acid, propionic acid, and butyric acid and (c) alleviated T2DM and jejunum injuries potentially based on SCFAs-GPR43/41-GLP-1 pathway.

CONCLUSION: LWDH could improve T2DM by regulating gut microbiota and SCFAs, and the therapeutic mechanism might be related to the SCFAs-GPR43/41-GLP-1 pathway.

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The potential mechanism of Liu–Wei–Di–Huang Pills in treatment of type 2 diabetic mellitus: from gut microbiota to short-chain fatty acids metabolism

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