Title: Dioxin-like PCB 126 increases intestinal inflammation and disrupts gut microbiota and metabolic homeostasis.
Authors: Petriello, Michael C; Hoffman, Jessie B; Vsevolozhskaya, Olga; Morris, Andrew J; Hennig, Bernhard
Published In Environ Pollut, (2018 Nov)
Abstract: The gut microbiome is sensitive to diet and environmental exposures and is involved in the regulation of host metabolism. Additionally, gut inflammation is an independent risk factor for the development of metabolic diseases, specifically atherosclerosis and diabetes. Exposures to dioxin-like pollutants occur primarily via ingestion of contaminated foods and are linked to increased risk of developing cardiometabolic diseases. We aimed to elucidate the detrimental impacts of dioxin-like pollutant exposure on gut microbiota and host gut health and metabolism in a mouse model of cardiometabolic disease. We utilized 16S rRNA sequencing, metabolomics, and regression modeling to examine the impact of PCB 126 on the microbiome and host metabolism and gut health. 16S rRNA sequencing showed that gut microbiota populations shifted at the phylum and genus levels in ways that mimic observations seen in chronic inflammatory diseases. PCB 126 reduced cecum alpha diversity (0.60 fold change; p = 0.001) and significantly increased the Firmicutes to Bacteroidetes ratio (1.63 fold change; p = 0.044). Toxicant exposed mice exhibited quantifiable concentrations of PCB 126 in the colon, upregulation of Cyp1a1 gene expression, and increased markers of intestinal inflammation. Also, a significant correlation between circulating Glucagon-like peptide-1 (GLP-1) and Bifidobacterium was evident and dependent on toxicant exposure. PCB 126 exposure disrupted the gut microbiota and host metabolism and increased intestinal and systemic inflammation. These data imply that the deleterious effects of dioxin-like pollutants may be initiated in the gut, and the modulation of gut microbiota may be a sensitive marker of pollutant exposures.
PubMed ID: 30373033
MeSH Terms: Animals; Dioxins/toxicity*; Gastrointestinal Microbiome/drug effects*; Homeostasis/drug effects*; Inflammation/chemically induced; Intestines; Male; Metabolomics; Mice; Microbiota/drug effects; Polychlorinated Biphenyls/toxicity*; Polychlorinated Dibenzodioxins; RNA, Ribosomal, 16S/genetics; Toxicity Tests