The Potential Role of Intestinal Microbiota on the Intestine-Protective and Lipid-Lowering Effects of Berberine in Zebrafish (Danio rerio) Under High-Lipid Stress.
Study Goal
The researchers aimed to investigate whether berberine's lipid-lowering effects are linked to its regulation of intestinal microbiota, particularly BSH-producing bacteria.
Results Summary
Berberine supplementation significantly reduced hepatic triglyceride and cholesterol levels, downregulated lipogenesis and proinflammatory cytokines, and increased beneficial bacteria abundance, particularly BSH-producing strains. However, combining berberine with antibiotics diminished these benefits, suggesting microbiota-dependent mechanisms.
Population
Zebrafish (Danio rerio) fed experimental diets.
Effective Dosage
Not specified
Duration
30 days
Interactions
Antibiotic cocktail reduced berberine's efficacy.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
berberine supplementation | increase | weight gain | zebrafish (Danio rerio) | - | significantly greater | #1 |
berberine supplementation | increase | feed intake | zebrafish (Danio rerio) | - | significantly greater | #2 |
high-lipid diet | increase | hepatic triglyceride (TG) levels | zebrafish (Danio rerio) | - | significantly upregulated | #3 |
high-lipid diet | increase | total cholesterol (TC) levels | zebrafish (Danio rerio) | - | significantly upregulated | #4 |
high-lipid diet | increase | lipogenesis | zebrafish (Danio rerio) | - | significantly upregulated | #5 |
high-lipid diet | increase | proinflammatory cytokine gene expression | zebrafish (Danio rerio) | - | significantly upregulated | #6 |
berberine supplementation | decrease | hepatic triglyceride (TG) levels | zebrafish (Danio rerio) | - | significantly downregulated | #7 |
berberine supplementation | decrease | total cholesterol (TC) levels | zebrafish (Danio rerio) | - | significantly downregulated | #8 |
berberine supplementation | decrease | lipogenesis | zebrafish (Danio rerio) | - | significantly downregulated | #9 |
berberine supplementation | decrease | proinflammatory cytokine gene expression | zebrafish (Danio rerio) | - | significantly downregulated | #10 |
berberine supplementation | increase | intestinal and/or hepatic farnesoid X receptor (fxr) expression | zebrafish (Danio rerio) | - | exhibited the opposite trend | #11 |
berberine supplementation | increase | Takeda G protein-coupled receptor 5 (tgr5) expression | zebrafish (Danio rerio) | - | exhibited the opposite trend | #12 |
berberine supplementation | increase | lipolysis genes expression | zebrafish (Danio rerio) | - | exhibited the opposite trend | #13 |
berberine supplementation | increase | zonula occludens 1 (zo1) expression | zebrafish (Danio rerio) | - | exhibited the opposite trend | #14 |
antibiotic cocktail | increase | hepatic TG content | zebrafish (Danio rerio) | - | significantly greater | #15 |
antibiotic cocktail | increase | proinflammatory cytokine expression | zebrafish (Danio rerio) | - | significantly greater | #16 |
antibiotic cocktail | decrease | intestinal bile salt hydrolase (BSH) activity | zebrafish (Danio rerio) | - | significantly lower | #17 |
antibiotic cocktail | decrease | intestinal and/or hepatic fxr expression | zebrafish (Danio rerio) | - | significantly lower | #18 |
antibiotic cocktail | decrease | intestinal and/or hepatic tgr5 expression | zebrafish (Danio rerio) | - | significantly lower | #19 |
high-lipid diet | decrease | abundance of certain probiotic bacteria (e.g., Microbacterium, Cetobacterium, and Gemmobacter) | zebrafish (Danio rerio) | - | decreased | #20 |
high-lipid diet | increase | pathways involved in cytochrome P450 | zebrafish (Danio rerio) | - | significantly increased | #21 |
high-lipid diet | increase | p53 signaling pathways | zebrafish (Danio rerio) | - | significantly increased | #22 |
high-lipid diet | increase | ATP-binding cassette (ABC) transporters pathways | zebrafish (Danio rerio) | - | significantly increased | #23 |
berberine supplementation | increase | some probiotic bacteria abundance, particularly BSH-producing bacteria (e.g., Escherichia Shigella) | zebrafish (Danio rerio) | - | increased | #24 |
antibiotic cocktail | decrease | abundance of BSH-producing bacteria (e.g., Bifidobacterium and Enterococcus) | zebrafish (Danio rerio) | - | reduced | #25 |
antibiotic cocktail | decrease | pathways related to Notch signaling | zebrafish (Danio rerio) | - | reduced | #26 |
antibiotic cocktail | decrease | pathways related to Wnt signaling | zebrafish (Danio rerio) | - | reduced | #27 |
Background: Berberine has extremely low oral bioavailability, but shows a potent lipid-lowering effect, indicating its potential role in regulating intestinal microbiota, which has not been investigated. Methods: In the present study, five experimental diets, a control diet (Con), a high-lipid diet (HL), and high-lipid·diets·supplemented with an antibiotic cocktail (HLA), berberine (HLB), or both (HLAB) were fed to zebrafish (Danio rerio) for 30 days. Results: The HLB group showed significantly greater weight gain and feed intake than the HLA and other groups, respectively (p < 0.05). Hepatic triglyceride (TG) and total cholesterol (TC) levels, lipogenesis, and proinflammatory cytokine gene expression were significantly upregulated by the high-lipid diet, but significantly downregulated by berberine supplementation. Conversely, the expression levels of intestinal and/or hepatic farnesoid X receptor (fxr), Takeda G protein-coupled receptor 5 (tgr5), lipolysis genes, and zonula occludens 1 (zo1) exhibited the opposite trend. Compared with the HLB group, the HLAB group displayed significantly greater hepatic TG content and proinflammatory cytokine expression, but significantly lower intestinal bile salt hydrolase (BSH) activity and intestinal and/or hepatic fxr and tgr5 expression levels. The HL treatment decreased the abundance of certain probiotic bacteria (e.g., Microbacterium, Cetobacterium, and Gemmobacter) and significantly increased the pathways involved in cytochrome P450, p53 signaling, and ATP-binding cassette (ABC) transporters. The HLB group increased some probiotic bacteria abundance, particularly BSH-producing bacteria (e.g., Escherichia Shigella). Compared with the HLB group, the abundance of BSH-producing bacteria (e.g., Bifidobacterium and Enterococcus) and pathways related to Notch signaling and Wnt signaling were reduced in the HLAB group. Conclusions: This study revealed that berberine's lipid-lowering and intestine-protective effects are closely related to the intestinal microbiota, especially BSH-producing bacteria.