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Published on: June 27, 2014
Glycodeoxycholic acid alleviates central precocious puberty by modulating gut microbiota and metabolites in high-fat
Nan Wu1, Xin Jiang1, Yanan Liu2
1Microbiome-X, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China.
Insights
Glycodeoxycholic acid (GDCA) may treat central precocious puberty (CPP) by altering gut bacteria and oxidative stress. GDCA treatment in rats delayed puberty onset and modulated key regulatory factors, suggesting a therapeutic potential for CPP.
Area of Science:
- Pediatric Endocrinology
- Metabolomics
- Gut Microbiome Research
Background:
- Central precocious puberty (CPP) is a common pediatric endocrine disorder with unclear regulatory mechanisms.
- Emerging evidence suggests a link between bile acids (BAs) and CPP, but their specific roles and pathways are poorly understood.
Purpose of the Study:
- To investigate the role of bile acids in the development of high-fat diet-induced CPP in female rats.
- To identify metabolites and gut microbiota alterations associated with CPP and their impact on Sirt1 and Kiss1 expression.
Main Methods:
- Untargeted metabolomics and targeted bile acid analysis were performed on serum samples from rats with diet-induced CPP.
- Bile acids were administered to CPP rats, and their effects on puberty onset, gut microbiota, and metabolic pathways were assessed.
- 16S rRNA sequencing and metabolomics were used to analyze gut microbiota and metabolites.
Main Results:
- Female rats with CPP showed reduced levels of glycodeoxycholic acid (GDCA) and glycoursodeoxycholic acid (GUDCA).
- GDCA treatment delayed puberty onset and altered gut microbiota, oxidative stress, and fatty acid metabolism.
- Oxidative stress metabolites mediated the reduction of Sirt1 expression, influenced by specific gut bacteria like Lachnospiraceae UCG-001.
Conclusions:
- GDCA demonstrates potential therapeutic effects for CPP.
- The mechanism involves modulation of gut microbiota, serum metabolites, and Sirt1 expression.
- This study highlights a novel pathway for CPP treatment involving bile acid-microbiota interactions.
Objective:
Central precocious puberty (CPP) is a common pediatric endocrine disorder and a significant global public health concern. Emerging evidence suggests an association between bile acids (BAs) and CPP, although their regulatory roles and underlying mechanisms remain poorly understood.
Methods:
We conducted untargeted metabolomics and targeted BA analysis on serum samples from female rats with high-fat diet-induced CPP to identify metabolites potentially involved in regulating puberty through modulation of Sirt1 and Kiss1 expression in the hypothalamus. Identified BAs were then administered via gavage to female rats with CPP to assess their effects. To explore the mechanisms by which these BAs affect the development of CPP, gut microbiota and their metabolites were analyzed using 16S rRNA sequencing and untargeted metabolomics.
Results:
Our findings revealed significant reductions in glycodeoxycholic acid (GDCA) and glycoursodeoxycholic acid (GUDCA) levels in female rats with CPP. GDCA treatment delayed the onset of puberty, accompanied by alterations in the gut microbiota functions and metabolic pathways related to oxidative stress (OS) and fatty acid metabolism. Mediation analysis suggested that OS-related metabolites, including gamma-glutamylcysteine and malonic acid, which increased with the abundance of Lachnospiraceae UCG-001, facilitated the reduction of Sirt1 expression. Additionally, pregnenolone appeared to suppress the beneficial effect of Parasutterella in enhancing Sirt1 expression.
Conclusion:
This study demonstrates that GDCA exhibits a potential therapeutic effect on CPP through a unique mechanism that involves gut microbiota modulation, alterations in serum metabolites, and changes in the expression of key regulatory factors Sirt1.
