Table 3.

Persistent Organic Pollutants and the Gut Microbiome

Chemical	Exposure Window	Dose	Model	Sex & Sex Differences	Effect on Gut Microbiota	Conclusions	References
PCB mixture	Developmental	0, 0.1, 1, or 6 mg/kg/day starting 2 weeks before gestation and continuing through PND 21	Congenic wildtype (WT) (75% C57BL/6 and 25% Sv129) DM mice (mutations in FMR1 and RyR)	No sex effects were observed, so all the data are combined and represented as equal proportions of males and females	↑ Proteobacteria phylum, specifically within the Deltaproteobacteria and Betaproteobacteria class ↑ Deferribacteres phylum was identified in DM mice compared with WT mice following exposure to 1 mg/kg/day PCB dose ↓ Proteobacteria, Bacteroidales family S7-25, and Alistipes in WT mice exposed to PCB compared with control	Increased gut permeability in juvenile double mutant (DM) and WT mice Genes of some inflammatory markers were significantly altered in treatment groups (regIIIgamma) of the same genotype. Gut microbiota were altered significantly when comparing WT and DM mice. However, PCB exposure also altered gut microbiota in WT mice when compared with control	Rude et al. (2019)
PCB-126	Adult, 7 weeks old	0 or 1 µmol/kg/day at weeks 2 and 4	Ldlr−/− mice	Male	↓ α-Diversity in cecum ↑ Firmicutes to Bacteroidetes ratio (F/B ratio)	PCB126 exposure altered the gut microbiota and host metabolism Increased intestinal and systemic inflammation	Petriello et al. (2018)
Atrazine, estradiol, PCB126, PCB153	Adult (4 months)	DMSO or 1.0 µg/l of environmental pollutant mixture	Zebrafish	Males and females Sex-specific xenobiotic responses	↑ Aeromonas in females	Estrogen receptor and aryl hydrocarbon receptor regulated the gut microbiota and host metabolism PCB exposure increased Aeromonas in females, but not males. The increase in Aeromonas was also positively correlated with oxidative damage Histophilus, Mannheimia, and Blastococcus were positively correlated with the integrity of the intestinal epithelial barrier PCB exposure in males, but not females significantly decreased serotonin levels and tight junction protein 2 compared with control	Chen et al. (2018b)
PCB congeners (PCB153, PCB138, PCB180)	Adults 11–13 months of age	Exercise for 5 days followed by 2 days of oral exposure to PCB mixture (150 µmol/kg)	C57Bl/6J mice	Males	↓ Proteobacteria (Pseudomonas plecoglossicida strain CGMCC 2093, P. plecoglossicida strain R18, Pseudomonas putida strain SRI156) and Firmicutes (Streptococcus infantis) phyla ↑ Candidatus aquirestis calciphila (fold change 1.9), Staphylococcus epidermidis (fold change 1.7), Bacteroides thetaiotaomicron strain 8669 (fold change 1.6), Tropheryma whipplei (fold change 1.5), Corynebacteriaceae, Verrucomicrobiaceae, Ulvophyceae, Porphyromonadaceae	PCB exposure altered gut microbiome, but voluntary exercise attenuated PCB-induced changes in gut microbiome PCB exposure decreased the abundance of 1133 bacterial taxa and increased the abundance of 90 taxa compared with control	Choi et al. (2013)
PAH parent compounds: naphthalene, phenanthrene, pyrene, and benzo(a)pyrene	In vitro	62.5 nmol	In vitro SHIME	Not applicable	Not specified	The microbiome in colon biotransformed PAH to have estrogenic activity	Van de Wiele et al. (2005)
PAH	Information not available	No exposure to oil (northern Norway area) or 0.01 ppm exposure to oil (southern Norway area)	Atlantic cod (Gadus Morhua)	Not applicable	Clean water fish: Fusobacteria and Proteobacteria were the most abundant, followed by Firmicutes and Bacteroidetes. Fish exposed to oil-contaminated waters showed dominance in Firmicutes, followed by Proteobacteria, Bacteroidetes, and Fusobacteria. Vibrionales was the most abundant order identified	Fish guts from a clean area had a lower microbial community richness compared with the fish guts from oil contaminated waters	Walter et al. (2019)
PFBS	In utero exposure (eggs exposed to PFBS)	0, 1.0, 2.9, 9.5 µg/l for the entire lifecycle	Marine medaka	Males and females Greater bioaccumulation of PFBS in males than females at all doses (1.0, 2.9, and 9.5 µg/l) Males had greater inflammatory responses than females Females exposed to PFBS had impaired lipid metabolism	Intestines of F0-exposed males: ↑ Cetobacterium (2.9 µg/l) compared with control ↓ Vibrio in F1 females after exposure of F0 parents to 9.5 µg/l PDBS ↑ Planctomyces and Lutimonas F1 intestines after parental exposure to 9.5 µg/l PFBS	PFBS exposure affected gut microbiota in fertile adults, and this persisted in the offspring Cetobacterium was significantly and positively correlated with host TJP2 expression, a biomarker of epithelial barrier integrity	Chen et al. (2018a)
PFAS: F-53B	Adult, 6 weeks old	0, 1, 3, or 10 µg/l for 10 weeks	C57Bl/6 mice	Males and females F-53B did not cause a sex-dependent effect in mice from an immune perspective	↓ Abundance of Firmicutes ↑ Verrucomicrobia after subchronic exposure. Bacteroides had no change. Akkermansia increased significantly in males but did not change significantly in females; Parabacteroides decreased significantly in females but showed no variation in males	MUC2 protein decreased in response to PFAS, but transcription increased in response to PFAS, possibly due to a compensatory phenomenon PFAS increased LPS in serum; increased MCP-1 markedly in males and females after treatment in colon; Tlr4, NFkB, Il1$\beta ,\mathrm{ }Il6,\mathrm{ }\mathit{Tnf},\mathrm{ }\mathit{Ifn}\mathrm{ }\mathrm{genes}\mathrm{ }\mathrm{were}\mathrm{ }\mathrm{all}\mathrm{ }\mathrm{upregulated}\mathrm{ }$ TNF-$\mathrm{\alpha }\mathrm{ }$protein also upregulated. At 10 µg, PFAS increased CD83 dendritic cells and decreased sIgA levels in the colon F-53B exposure decreased mucous production and decreased gene expression of ion transporters in both males and females.	Pan et al. (2019)
BDE-47	In utero and lactational exposure	0, 0.002, and 0.2 mg/kg BDE-47 from GD 6 to PND 21. Male mice selected to be either on normal diet or HFD for 14 weeks	Primigravida female ICR mice	Only male mice were selected for analysis	↓ $\mathrm{\alpha }$-Diversity in fecal extracts ↑ In the relative abundances of Parasutterella and Gemella ↓ In the relative abundances of Christensenellaceae, Atopostipes, and Bacillus ↑ In relative abundances of Candidatus saccharimonas, Ruminococcaceae, Staphylococcus, Gemella, Eubacterium, Corynebacterium, Paenalcaligenes when compared with normal diet + vehicle group	Exposure to BDE-47 reduced alpha diversity in fecal extracts, altered microbial composition, and impaired metabolic functions, including impaired glucose homeostasis, hepatic steatosis, and injury	Wang et al. (2018a)
BDE-47 or BDE-99	Adult, 9 weeks old	0 or 100 µmol/kg/day for 4 days	C57Bl/6 mice (conventional and germ-free)	Males	PBDE exposure altered 23 gut microbial taxa	PBDE exposure in the intestinal microbiome decreased branched-chain and aromatic amino acid metabolites	Scoville et al. (2019)
OBS	Adult, 6 weeks old	0, 0.1, 1, or 10 µg/l	ICR mice	Males	Not applicable	No microbiome data—but the authors reported decreased mucus secretion and gut barrier dysfunction in treatment groups compared with control. Hepatic transcriptomics and metabolomics showed lipid metabolism disorders	Wang et al. (2019b)
HCH	Adult	N/A	Mothers-humans	Males and females were combined for analyses, so sex differences were not determined	↓ In microbial diversity in colostrum with ↑ HC levels. Proteobacteria and Firmicutes were main phyla in colostrum. Microbial diversity at the genus level differed between samples (dose-dependent)	HCH altered microbial composition in human colostrum and the colonization of the infant gut	Tang et al. (2019)
Endosulfan	Adult, 8 weeks old	0, 0.5, or 3.5 mg/kg/day for 2 weeks	ICR mice	Male	Not applicable	Endosulfan exposure-induced liver injury and disrupted amino acid, lipid, and gut microbiota metabolism	Zhang et al. (2017)
TCDD	Juvenile, 4 weeks old	0 or 30 µg/kg/day every 4 days for 28 days	Gnotobiotic C57Bl/6	Female	↑ Segmented filamentous bacteria (SFB)↓ Bacteroides fragilis	TCDD-induced host response was significantly modulated by the presence of SFB in the gut microbiome	Stedtfeld et al. (2017b)
TCDD	Juvenile, PND 28, 29	0–30 µg/kg/day for 28 and 92 days with the latter having a 30-day recovery period	C57Bl/6 mice	Female	↑ Enterobacteriaceae	TCDD exposure enriched ARG and MGE-harboring members of Enterobacteriaceae in the gut microbiome	Stedtfeld et al. (2017c)
TCDD	Adult, 5–8 weeks old	0, 0.1, 1.0, and 10 µg/kg/day for 4 days	B6C3F1 mice	Female	Expression of SFB in mouse ileum	Addition of activated carbon decreased the bioavailability of TCDD in the host and may have influenced the gut microbiome	Stedtfeld et al. (2017a)
TCDD	Adult, 6 and 7 weeks old	0 or 6 µg/kg biweekly for 26 weeks	CD-1 mice in a prediabetic hyperglycemic state via streptozotocin intraperitoneal injection	Male	↑ Firmicutes ↓ Bacteroidetes ↑ Lactobacillaceae and Desulfovibrionaceae ↓ Prevotellaceae and Actinobacteria cluster ACK M1	Dysregulated gut microbiome may have contributed to liver and immune toxicity	Lefever et al. (2016)
TCDD, PhIP, HBD, B[a]P, deltamethrin, and PAHs	Adults	0.005, 0.90, 2.60, 5, 21, and 38 µg/ml	Human in vitro cultured feces TC7 cells (clone of parenteral Caco-2 epithelial cell line)	Not applicable	Not applicable	Pollutant disturbance may have promoted inflammation with the release of IL-8 from intestinal epithelial cells	Defois et al. (2018)
TCDF	Adult (8 weeks old)	0 or 24 µg/kg/day for 5 days	C57Bl/6J mice	Males	↓ F/B ratio ↑ In Butyrivibrio spp. and Flavobacteria ↓ In Oscillibacter and Clostridia ↓ SFB	Changes in microbiota were associated with marked increases in bile acids, SCFA, altered liver function, increased intestinal inflammation, and inhibited signaling of FXR, a key regulator of fat and glucose metabolism	Zhang et al. (2015a)

Abbreviations: α-HBCD, α-hexabromocyclododecane; γ-HBCD, γ-hexabromocyclododecane; BDE-47, 2,2′,4,4′-tratrabromodiphenyl ether; DMSO, dimethyl sulfoxide; F-53B, 6:2 chlorinated polyfluorinated ether sulfonate; FXR, farnesoid X receptor; HCH, hexachlorocyclohexane; OBS, sodium p-perfluorous nonenoxybenzene sulfonate; PAH, polycyclic aromatic hydrocarbons; PBDE, polybrominated diphenyl ether; PCB, polychlorinated biphenyls; PFAS, per- and polyfluoroalkylated substances; PFBS, perfluorobutane sulfonate; SCFA, short-chain fatty acid; SHIME, Simulator of the Human Intestinal Microbial Ecosystem; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDF, 2,3,7,8-tetrachloro dibenzofuran.