Insulin Sensitivity-Enhancing Activity of Phlorizin Is Associated with Lipopolysaccharide Decrease and Gut Microbiota...

Area of Science:

• Metabolic Syndrome
• Gut Microbiome Research
• Pharmacology

Background:

• Phlorizin, found in fruits, has known antidiabetic effects via sodium-glucose symporter (SGLT) inhibition.
• Poor oral bioavailability and systemic metabolism limit phlorizin's therapeutic potential.
• The gut microbiota may represent an alternative target for phlorizin's action.

Purpose of the Study:

• To investigate the effects of phlorizin on metabolic syndrome in obese diabetic mice.
• To explore the role of gut microbiota modulation in phlorizin's antidiabetic mechanism.

Main Methods:

• Obese diabetic mice (db/db) and controls (db/+) were treated with phlorizin or vehicle for 10 weeks.
• Evaluated body weight, energy intake, serum lipopolysaccharides (LPS), insulin resistance, and fecal short-chain fatty acids (SCFAs).
• Analyzed gut microbiome composition using 16S rRNA gene denaturing gradient gel electrophoresis (DGGE) and quantitative PCR.

Main Results:

• Phlorizin treatment significantly reduced weight gain, energy intake, serum LPS, and insulin resistance.
• Fecal levels of total SCFAs, particularly butyric acid, were significantly increased.
• Phlorizin enhanced gut microbial diversity and promoted the growth of Akkermansia muciniphila and Prevotella, improving gut microbiota structure.

Conclusions:

• Phlorizin effectively prevents metabolic syndrome in diabetic mice, suggesting a mechanism beyond SGLT inhibition.
• Phlorizin's hypoglycemic action is linked to reduced LPS and favorable gut microbiota alterations.
• Phlorizin modifies the gut microbial community, leading to decreased LPS and increased beneficial SCFA-producing bacteria.