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Broad-spectrum antibiotics alter the microbiome, increase intestinal fxr, and decrease hepatic steatosis in zebrafish
Kathryn M Maselli1, Kristin Gee1, Mubina Isani1
1Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, California.
Broad-spectrum antibiotics in zebrafish with short bowel syndrome (SBS) altered the microbiome, reduced inflammation, and prevented liver steatosis. This research identifies potential therapeutic targets for SBS and related liver disease (IFALD).
Area of Science:
- Gastroenterology
- Microbiology
- Hepatology
Background:
- Short bowel syndrome (SBS) involves gut microbiome changes, inflammation, and liver disease (IFALD).
- Patients often have a history of abdominal issues and broad-spectrum antibiotic use.
- Zebrafish models can mimic human SBS complications.
Purpose of the Study:
- To investigate if antibiotics in SBS zebrafish replicate human systemic effects.
- To identify druggable targets for managing SBS and IFALD.
- To explore antibiotic impact on gut microbiome and liver health in SBS.
Main Methods:
- Administered broad-spectrum antibiotics to zebrafish with SBS.
- Analyzed changes in microbiome diversity and composition.
- Measured gene expression (tlr4, fxr, cyp7a1) and hepatic steatosis.
Main Results:
- Antibiotics altered the microbiome, decreasing diversity.
- Reduced intestinal and hepatic inflammation was observed.
- Hepatic steatosis development was decreased, with altered gene expression.
Conclusions:
- Antibiotic administration in SBS zebrafish created distinct states regarding liver fat accumulation.
- This model offers insights into managing SBS and IFALD.
- Findings suggest potential therapeutic avenues targeting microbiome and inflammation.
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