title: Oral imazalil exposure induces gut microbiota dysbiosis and colonic inflammation in mice.
abstract: The fungicide imazalil (IMZ) is used extensively in vegetable and fruit plantations and as a post-harvest treatment to avoid rot. Here, we revealed that ingestion of 25, 50 and 100 mg IMZ kg(-1) body weight for 28 d induced gut microbiota dysbiosis and colonic inflammation in mice. The relative abundance of Bacteroidetes, Firmicutes and Actinobacteria in the cecal contents decreased significantly after exposure to 100 mg kg(-1) IMZ for 28 d. In feces, the relative abundance in Bacteroidetes, Firmicutes and Actinobacteria decreased significantly after being exposed to 100 mg kg(-1) IMZ for 1, 14 and 7 d, respectively. High throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene revealed a significant reduction in the richness and diversity of microbiota in cecal contents and feces of IMZ-treated mice. Operational taxonomic units (OTUs) analysis identified 49.3% of OTUs changed in cecal contents, while 55.6% of OTUs changed in the feces after IMZ exposure. Overall, at the phylum level, the relative abundance of Firmicutes, Proteobacteria and Actinobacteria increased and that of Bacteroidetes decreased in IMZ-treated groups. At the genus level, the abundance of Lactobacillus and Bifidobacterium decreased while those of Deltaproteobacteria and Desulfovibrio increased in response to IMZ exposure. In addition, it was observed that IMZ exposure could induce colonic inflammation characterized by infiltration of inflammatory cells, elevated levels of lipocalin-2 (lcn-2) in the feces, and increased mRNA levels of Tnf-α, IL-1β, IL-22 and IFN-γ in the colon. Our findings strongly suggest that ingestion of IMZ has some risks to human health.
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Cuiyuan
authors.initials: C
authors.lastname: Jin
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Zhaoyang
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310032, China. Electronic address: jinyx@zjut.edu.cn.
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
mesh_terms: D039903:Actinobacteria / Q000187:drug effects / Q000235:genetics; D000818:Animals; D041963:Bacteroidetes / Q000187:drug effects / Q000235:genetics; D003106:Colon / Q000187:drug effects / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D064806:Dysbiosis / Q000139:chemically induced* / Q000276:immunology / Q000382:microbiology; D005243:Feces / Q000382:microbiology; D005659:Fungicides, Industrial / Q000633:toxicity*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D007093:Imidazoles / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D020560:Proteobacteria / Q000187:drug effects / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D005659:Fungicides, Industrial; D007093:Imidazoles; D012336:RNA, Ribosomal, 16S; D014409:Tumor Necrosis Factor-alpha; C017435:enilconazole
keywords: Colonic inflammation; Gut microbiota; Imazalil; Mice