Role of gut microbiota in a zebrafish model with chemically induced enterocolitis involving toll-like receptor signaling pathways.
OBJECTIVE
It is believed that inflammatory bowel disease (IBD) involves a breakdown in interactions between the resident commensal microbiota and the host immune response. Recent studies have revealed that gut physiology and pathology relevant to human IBD can be rapidly modeled in zebrafish larvae with a number of advantages compared with murine models. The objective of this study was to evaluate the role of gut microbiota in zebrafish models with IBD-like enterocolitis.


METHODS
IBD-like enterocolitis was induced by exposing larval zebrafish to 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). Assays were performed using larval zebrafish collected at 8 and 10 days postfertilization (dpf ).


RESULTS
In the absence of gut microbiota, the TNBS-induced enterocolitis was less extensive. The expression of toll-like receptor 3 (TLR3) and the TLRs signaling pathway molecules MyD88 and TRIF, the activation of NF-κB, and the production of inflammatory cytokine tumor necrosis factor-α were stimulated in TNBS-treated zebrafish but there was no corresponding alteration in germ-free fish. With microbial colonization, all results reverted to a pattern similar to that observed in conventionally reared zebrafish.


CONCLUSIONS
We described the key role of gut microbiota in the etiology of a chemically induced larval zebrafish IBD-like model, showing an involvement of TLR signaling pathways.
Research Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University , Nanjing, China .
Qi
Q
He
Lin
L
Wang
Fan
F
Wang
Qiurong
Q
Li
D000818:Animals; D004195:Disease Models, Animal; D004760:Enterocolitis / Q000139:chemically induced / Q000382:microbiology* / Q000503:physiopathology; D041981:Gastrointestinal Tract / Q000382:microbiology* / Q000503:physiopathology*; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000382:microbiology* / Q000503:physiopathology; D064307:Microbiota; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology; D015027:Zebrafish / Q000382:microbiology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism
D051193:Toll-Like Receptors; D029961:Zebrafish Proteins; D014302:Trinitrobenzenesulfonic Acid