Dietary Exposure to the Environmental Chemical, PFOS on the Diversity of Gut Microbiota, Associated With the Development of Metabolic Syndrome

Abstract

The gut microbiome is a dynamic ecosystem formed by thousands of diverse bacterial species. This bacterial diversity is acquired early in life and shaped over time by a combination of multiple factors, including dietary exposure to distinct nutrients and xenobiotics. Alterations of the gut microbiota composition and associated metabolic activities in the gut are linked to various immune and metabolic diseases. The microbiota could potentially interact with xenobiotics in the gut environment as a result of their board enzymatic capacities and thereby affect the bioavailability and toxicity of the xenobiotics in enterohepatic circulation. Consequently, microbiome-xenobiotic interactions might affect host health. Here, we aimed to investigate the effects of dietary perfluorooctane sulfonic acid (PFOS) exposure on gut microbiota in adult mice and examine the induced changes in animal metabolic functions. In mice exposed to dietary PFOS for 7 weeks, body PFOS and lipid contents were measured, and to elucidate the effects of PFOS exposure, the metabolic functions of the animals were assessed using oral glucose-tolerance test and intraperitoneal insulin-tolerance and pyruvate-tolerance tests; moreover, on Day 50, cecal bacterial DNA was isolated and subject to 16S rDNA sequencing. Our results demonstrated that PFOS exposure caused metabolic disturbances in the animals, particularly in lipid and glucose metabolism, but did not substantially affect the diversity of gut bacterial species. However, marked modulations were detected in the abundance of metabolism-associated bacteria belonging to the phyla Firmicutes, Bacteroidetes, Proteobacteria, and Cyanobacteria, including, at different taxonomic levels, Turicibacteraceae, Turicibacterales, Turicibacter, Dehalobacteriaceae, Dehalobacterium, Allobaculum, Bacteroides acidifaciens, Alphaproteobacteria, and 4Cod-2/YS2. The results of PICRUSt analysis further indicated that PFOS exposure perturbed gut metabolism, inducing notable changes in the metabolism of amino acids (arginine, proline, lysine), methane, and a short-chain fatty acid (butanoate), all of which are metabolites widely recognized to be associated with inflammation and metabolic functions. Collectively, our study findings provide key information regarding the biological relevance of microbiome-xenobiotic interactions associated with the ecology of gut microbiota and animal energy metabolism.

Keywords: PFOs; bacterial diversity; energy metabolism; gut microbiome; microbiome-xenobiotic interaction.

FIGURE 1

Effect of 7-week dietary PFOS exposure on liver weight and triglyceride content in mice. (A) Absolute liver weight, (B) liver index, (C) liver triglyceride level, and (D) serum triglyceride level were measured on Day 50 after PFOS treatment. Data are presented as means ± SD; ^∗p < 0.05 versus control group. AC, control; AL, 0.3 μg/g body weight/day; AH, 3 μg/g body weight/day.

FIGURE 2

Effect of 7-week dietary PFOS exposure in mice, examined using (A) oral glucose-tolerance test (OGTT), (B) insulin-tolerance test (ITT), and (C) pyruvate-tolerance test (PTT). Left panels: changes in serum glucose levels against time in the assays; right panels: area under curve (AUC) values of the respective assays. Data are presented as means ± SD; ^∗p < 0.05 versus control group. AC, control; AL, 0.3 μg/g body weight/day; AH, 3 μg/g body weight/day.

FIGURE 3

Effect of 7-week dietary PFOS exposure on gut bacterial structure in mice. (A) Comparison of operational taxonomic units (OTUs); different colors represent distinct groups: (i) control (AC), (ii) low-dose PFOS exposure (AL), and (iii) high-dose PFOS exposure (AH). The intersection represents the set of OTUs commonly present in the counterpart groups. Venn diagram was drawn using VennDiagram software R (v3.0.3). (B) Changes in observed species number, Chao1 index, Ace index, Shannon’s diversity, and Simpson’s diversity; the results suggest that dietary PFOS intake exerted no effect on the species diversity of the gut bacterial community.

FIGURE 4

Effect of 7-week dietary PFOS exposure on gut microbiome community at distinct taxonomic levels. (A) Phylogenetic tree diagram at genus level. The same color indicates the same phylum. Taxonomic composition distributions in control (AC), low-dose PFOS-exposure (AL), and high-dose PFOS-exposure (AH) groups are shown at the levels of (B) phylum, (C) class, (D) order, (E) family, and (F) genus.