Subacute Exposure to an Environmentally Relevant Dose of Di-(2-ethylhexyl) Phthalate during Gestation Alters the Cecal Microbiome, but Not Pregnancy Outcomes in Mice
Abstract
:1. Introduction
2. Materials and Methods
2.1. Chemicals
2.2. Experimental Animals
2.3. Experimental Design
2.4. Cecal Collection
2.5. DNA Isolation and Quantification
2.6. Processing of Microbial Genomic DNA for 16S rRNA Gene and Metagenomic Sequencing
2.7. Bioinformatic Analyses of 16S rRNA Gene Data
2.8. Bioinformatic Analyses of Metagenomic Data
2.9. Pregnancy Outcomes
2.10. Statistical Analysis
3. Results
3.1. Cecal Microbiota
3.1.1. Alpha and Beta Diversity
3.1.2. Taxonomic Results
3.2. Cecal Microbiome
3.2.1. Alpha and Beta Diversity
3.2.2. Results from Functional Analysis
3.2.3. Gestational Outcomes and Weights in Dams
3.2.4. Outcomes in the F1 Pups
4. Discussion
5. Conclusions and Future Directions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Classification | Number of Taxa |
---|---|
Kingdom | 178 |
Phylum | 178 |
Class | 178 |
Order | 178 |
Family | 168 |
Genus | 66 |
Species | 4 |
Variable | Bray–Curtis | UniFrac | Weighted UniFrac |
---|---|---|---|
Trt | 0.012 | 0.009 | 0.017 |
Body weight | 0.452 | 0.433 | 0.082 |
Ovary weight | 0.483 | 0.461 | 0.585 |
Uterus weight | 0.649 | 0.057 | 0.872 |
Liver weight | 0.291 | 0.673 | 0.046 |
Spleen weight | 0.156 | 0.190 | 0.072 |
Library size | 0.477 | 0.624 | 0.108 |
Trt + Body Weight | NA | NA | 0.012 |
Trt + Uterus Weight | NA | 0.007 | NA |
Trt + Liver Weight | NA | NA | 0.008 |
Trt + Spleen Weight | NA | NA | 0.016 |
Pathway ID | Pathway | n | DE | P.DE |
---|---|---|---|---|
path:ko02040 | Flagellar assembly | 30 | 24 | 4.34 × 10−8 |
path:ko02030 | Bacterial chemotaxis | 21 | 16 | 2.70 × 10−5 |
path:ko03060 | Protein export | 18 | 12 | 2.02 × 10−3 |
path:ko00190 | Oxidative phosphorylation | 45 | 23 | 3.94 × 10−3 |
path:ko00720 | Carbon fixation pathways in prokaryotes | 53 | 26 | 4.60 × 10−3 |
path:ko02024 | Quorum sensing | 86 | 38 | 6.89 × 10−3 |
path:ko03440 | Homologous recombination | 21 | 12 | 1.19 × 10−2 |
path:ko00340 | Histidine metabolism | 20 | 11 | 2.26 × 10−2 |
path:ko01100 | Metabolic pathways | 898 | 304 | 2.45 × 10−2 |
path:ko00130 | Ubiquinone and other terpenoid-quinone biosynthesis | 18 | 10 | 2.71 × 10−2 |
path:ko00121 | Secondary bile acid biosynthesis | 3 | 3 | 3.02 × 10−2 |
path:ko01502 | Vancomycin resistance | 16 | 9 | 3.25 × 10−2 |
path:ko01200 | Carbon metabolism | 152 | 58 | 3.65 × 10−2 |
path:ko00020 | Citrate cycle (TCA cycle) | 37 | 17 | 4.11 × 10−2 |
path:ko00061 | Fatty acid biosynthesis | 17 | 9 | 5.04 × 10−2 |
path:ko00540 | Lipopolysaccharide biosynthesis | 25 | 12 | 5.75 × 10−2 |
path:ko03430 | Mismatch repair | 20 | 10 | 6.05 × 10−2 |
path:ko00250 | Alanine, aspartate, and glutamate metabolism | 36 | 16 | 6.37 × 10−2 |
path:ko01210 | 2-Oxocarboxylic acid metabolism | 28 | 13 | 6.43 × 10−2 |
path:ko01110 | Biosynthesis of secondary metabolites | 350 | 122 | 6.64 × 10−2 |
path:ko04142 | Lysosome | 8 | 5 | 6.73 × 10−2 |
path:ko00780 | Biotin metabolism | 13 | 7 | 7.48 × 10−2 |
path:ko00290 | Valine, leucine and isoleucine biosynthesis | 13 | 7 | 7.48 × 10−2 |
path:ko00531 | Glycosaminoglycan degradation | 6 | 4 | 7.99 × 10−2 |
path:ko00401 | Novobiocin biosynthesis | 6 | 4 | 7.99 × 10−2 |
path:ko03018 | RNA degradation | 16 | 8 | 9.01 x 10-2 |
path:ko00550 | Peptidoglycan biosynthesis | 32 | 14 | 9.06 × 10−2 |
path:ko03013 | RNA transport | 4 | 3 | 9.27 × 10−2 |
path:ko04214 | Apoptosis—fly | 2 | 2 | 9.71 × 10−2 |
path:ko00332 | Carbapenem biosynthesis | 2 | 2 | 9.71 × 10−2 |
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Chiu, K.; Bashir, S.T.; Gao, L.; Gutierrez, J.; de Godoy, M.R.C.; Drnevich, J.; Fields, C.J.; Cann, I.; Flaws, J.A.; Nowak, R.A. Subacute Exposure to an Environmentally Relevant Dose of Di-(2-ethylhexyl) Phthalate during Gestation Alters the Cecal Microbiome, but Not Pregnancy Outcomes in Mice. Toxics 2021, 9, 215. https://doi.org/10.3390/toxics9090215
Chiu K, Bashir ST, Gao L, Gutierrez J, de Godoy MRC, Drnevich J, Fields CJ, Cann I, Flaws JA, Nowak RA. Subacute Exposure to an Environmentally Relevant Dose of Di-(2-ethylhexyl) Phthalate during Gestation Alters the Cecal Microbiome, but Not Pregnancy Outcomes in Mice. Toxics. 2021; 9(9):215. https://doi.org/10.3390/toxics9090215
Chicago/Turabian StyleChiu, Karen, Shah Tauseef Bashir, Liying Gao, Jessica Gutierrez, Maria R. C. de Godoy, Jenny Drnevich, Christopher J. Fields, Isaac Cann, Jodi A. Flaws, and Romana A. Nowak. 2021. "Subacute Exposure to an Environmentally Relevant Dose of Di-(2-ethylhexyl) Phthalate during Gestation Alters the Cecal Microbiome, but Not Pregnancy Outcomes in Mice" Toxics 9, no. 9: 215. https://doi.org/10.3390/toxics9090215