Background: Di-(2-ethylhexyl) phthalate (DEHP), a predominant phthalate ester (PAE), exhibits various toxic potentials with environmental and human health risks. However, the chronic effects of DEHP exposure on gut microbiota and associated host's health are still largely unexplored. Here, zebrafish were exposed to relative environmental levels (0-100 μg/L) of DEHP from embryos to adult (3.5 months), then the developmental indexes and microbiota as well as the related energy metabolites in gut

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... issues were checked to unveil the effects during the growth progress. Results: The results indicated that the composition of gut microbiota was different among male and female adult zebrafish, and DEHP disrupted the diversity and richness of the bacterial community. The histopathological analysis of intestinal tissues revealed the decrease of villus length and tunica muscularis thickness, especially the goblet cells per villi in male fish. Moreover, energy metabolites in gut tissues were actively increased at lower levels groups, which probably contribute to the condition factor of host. For immune-related genes, the expression levels of il-8 was increased both in female and male fish in the lowest concentration (10 μg/L), but the tlr-5 and il-1β genes were in the different response with significantly decreased in female fish. Conclusion: Taken all together, those results indicated that chronic exposure to DEHP led to zebrafish obesity with the disturbed bacterial community in the gut and related metabolism pathways. Those findings provided deep insights on the perturbation of gut microbiota, metabolic homeostasis, and gender-based differences by DEHP exposure.