Microbiota dysbiosis associated with type 2 diabetes-like effects caused by chronic exposure to a mixture of chlorinated persistent organic pollutants in zebrafish [II]

Mixtures of chlorinated persistent organic pollutants (C-POPs-Mix) are chemically related risk factors for type 2 diabetes mellitus (T2DM); however, the effects of chronic exposure to C-POPs-Mix on microbial dysbiosis remain poorly understood. Herein, male and female zebrafish were exposed to C-POPs-Mix at a 1:1 ratio of five organochlorine pesticides and Aroclor 1254 at concentrations of 0.02, 0.1, and 0.5 µg/L for 12 weeks. We measured T2DM indicators in blood and profiled microbial abundance, richness, and evenness in the gut as well as transcriptomic and metabolomic alterations in the liver. Exposure to C-POPs-Mix significantly increased blood glucose levels while decreasing the abundance and alpha diversity of microbial communities only in females at concentrations of 0.02 and 0.1 µg/L. The majorly identified microbial contributors to microbial dysbiosis were Bosea minatitlanensis, Rhizobium tibeticum, Bifidobacterium catenulatum, B. adolescentis, and Collinsella aerofaciens. PICRUSt results suggested that altered pathways were associated with glucose and lipid production and inflammation, which are linked to changes in the transcriptome and metabolome of the zebrafish liver. Metagenomics outcomes revealed close relationships between intestinal and liver disruptions to T2DM-related molecular pathways. Thus, microbial dysbiosis in T2DM-triggered zebrafish occurred as a result of chronic exposure to C-POPs-Mix, indicating strong host–microbiome interactions. Overall design: Samples consisted of the control group and three treatment groups exposed to 0.02, 0.1, and 0.5 ug/L of C-POPs-Mix (containing five OCPs and Aroclor1254) for the mechanistic study to demonstrate the relationship between microbiota dysbiosis and type 2 diabetes in C-POPs-Mix exposed zebrafish. Six female livers were pooled for each group and used to perform RNA-seq on the Illumina HiSeq 2500 platform. For 16S rRNA-seq analysis, total genomic DNAs were individually extracted from five intestines in each group and sequenced by Illumina Miseq system.