PUBLICATION
Broad spectrum antibiotics alter the microbiome, increase intestinal fxr, and decrease hepatic steatosis in zebrafish short bowel syndrome
- Authors
- Maselli, K.M., Gee, K., Isani, M., Fode, A., Schall, K.A., Grikscheit, T.C.
- ID
- ZDB-PUB-200701-6
- Date
- 2020
- Source
- American journal of physiology. Gastrointestinal and liver physiology 319(2): G212-G226 (Journal)
- Registered Authors
- Keywords
- Farnesoid X receptor, Intestinal failure associated liver disease, Intestinal microbiome, Short bowel syndrome, Toll-like receptor 4
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/pharmacology*
- Fatty Liver/prevention & control*
- Receptors, Cytoplasmic and Nuclear/metabolism*
- Short Bowel Syndrome/microbiology*
- Zebrafish
- PubMed
- 32597709 Full text @ Am. J. Physiol. Gastrointest. Liver Physiol.
Citation
Maselli, K.M., Gee, K., Isani, M., Fode, A., Schall, K.A., Grikscheit, T.C. (2020) Broad spectrum antibiotics alter the microbiome, increase intestinal fxr, and decrease hepatic steatosis in zebrafish short bowel syndrome. American journal of physiology. Gastrointestinal and liver physiology. 319(2):G212-G226.
Abstract
Short bowel syndrome (SBS) is associated with changes in the intestinal microbiome and marked local and systemic inflammation. There is also a late complication of SBS, intestinal failure associated liver disease (IFALD) in which hepatic steatosis progresses to cirrhosis. Most patients with SBS arrive at massive intestinal resection after a contaminating intraabdominal catastrophe and have a history of exposure to broad spectrum antibiotics. We therefore investigated whether the administration of broad spectrum antibiotics in conjunction with SBS in zebrafish (ZF) would replicate these systemic effects observed in humans in order to identify potentially druggable targets to aid in the management of SBS and resulting IFALD. In zebrafish with SBS, broad spectrum antibiotics altered the microbiome, decreased inflammation, and reduced the development of hepatic steatosis. After two weeks of broad spectrum antibiotics, these fish exhibited decreased alpha diversity, with less variation in microbial community composition between SBS and sham fish. Additionally, administration of broad spectrum antibiotics was associated with decreased expression of intestinal toll-like receptor 4 (tlr4), increased expression of the intestinal gene encoding the Farnesoid X receptor (fxr), decreased expression of downstream hepatic cyp7a1, and decreased development of hepatic steatosis. SBS in zebrafish reproducibly results in increased epithelial surface area as occurs in human patients who demonstrate intestinal adaptation, but antibiotic administration in zebrafish with SBS reduced these gains with increased cell death in the intervillus pocket that contains stem/progenitor cells. These alternate states in SBS zebrafish might direct the development of future human therapies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping