RT Journal Article SR Electronic T1 Zebrafish modeling of intestinal injury, bacterial exposures and medications defines epithelial in vivo responses relevant to human inflammatory bowel disease JF Disease Models & Mechanisms JO Dis Models Mech FD The Company of Biologists Limited SP dmm037432 DO 10.1242/dmm.037432 VO 12 IS 8 A1 Chuang, Ling-shiang A1 Morrison, Joshua A1 Hsu, Nai-yun A1 Labrias, Philippe Ronel A1 Nayar, Shikha A1 Chen, Ernie A1 Villaverde, Nicole A1 Facey, Jody Ann A1 Boschetti, Gilles A1 Giri, Mamta A1 Castillo-Martin, Mireia A1 Thin, Tin Htwe A1 Sharma, Yashoda A1 Chu, Jaime A1 Cho, Judy H. YR 2019 UL http://dmm.biologists.org/content/12/8/dmm037432.abstract AB Genome-wide association studies have identified over 200 genomic loci associated with inflammatory bowel disease (IBD). High-effect risk alleles define key roles for genes involved in bacterial response and innate defense. More high-throughput in vivo systems are required to rapidly evaluate therapeutic agents. We visualize, in zebrafish, the effects on epithelial barrier function and intestinal autophagy of one-course and repetitive injury. Repetitive injury induces increased mortality, impaired recovery of intestinal barrier function, failure to contain bacteria within the intestine and impaired autophagy. Prostaglandin E2 (PGE2) administration protected against injury by enhancing epithelial barrier function and limiting systemic infection. Effects of IBD therapeutic agents were defined: mesalamine showed protective features during injury, whereas 6-mercaptopurine displayed marked induction of autophagy during recovery. Given the highly conserved nature of innate defense in zebrafish, it represents an ideal model system with which to test established and new IBD therapies targeted to the epithelial barrier.This article has an associated First Person interview with the first author of the paper.