Grantee Research Project Results
2019 Progress Report: Center for Children's Health, the Environment, Microbiome, and Metabolomics
EPA Grant Number: R836153Center: Center for Children’s Health, the Environment, Microbiome, and Metabolomics’ Center
Center Director: McCauley, Linda
Title: Center for Children's Health, the Environment, Microbiome, and Metabolomics
Investigators: McCauley, Linda
Current Investigators: McCauley, Linda , Ryan, P. Barry
Institution: Emory University
EPA Project Officer: Callan, Richard
Project Period: September 1, 2015 through August 31, 2019 (Extended to August 31, 2020)
Project Period Covered by this Report: September 1, 2018 through August 31,2019
Project Amount: $1,797,870
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text | Recipients Lists
Research Category: Human Health , Children's Health
Objective:
Aim 1: Characterize pre- and postnatal environmental exposures of African American (AA) mother-infant pairs in metropolitan Atlanta.
Aim 2: Investigate the independent and interactive effects of prenatal chemical exposures upon the composition of the maternal microbiome for pregnant AA women in metropolitan Atlanta.
Aim 3: Investigate the independent and interactive effects of prenatal chemical exposures upon birth outcomes for pregnant AA women in metropolitan Atlanta.
Progress Summary:
(1) Enrollment, Data Collection:
We have continued to implement all protocols and procedures for the recruitment and consent of subjects, the collection of data and specimens (questionnaire items, biological and household samples), and the handling, processing, and analysis of specimens that were developed and refined by the P1 Team during Year 1. During this Year, we maintained Emory Institutional Review Board approval for the P1 recruitment and data collection protocols; utilized data bases for participant and sample tracking; and maintained training of field staff in the consent, data collection, data and sample handling and processing procedures.
a. Prenatal: As of 12/15/2019, we have enrolled 387 pregnant women into the P50 protocol. Among the 387 enrolled pregnant women, the following completed the planned sample collections during the initial prenatal clinic visit (between 8-14 weeks’ gestation): 380 completed microbiome swab collections, 377 completed venous blood collection, and 372 completed urine sample collection. Of the 387 enrolled pregnant women, 312 have passed through the 20-30 week gestational age window for the home environmental assessment, with 181 women (58%) consenting to participate and completing the home assessments. Our team continues to reach out to the enrolled women who are approaching the gestational age window for the home environmental assessments to schedule those home visits, and we are continuing to recruit and enroll into the Parent Study and P1. All biological and environmental specimens from enrolled subjects have been processed and entered into a long-term biorepository created for this project. We have maintained participant tracking in a Microsoft Access database and participant survey and assay data in a RedCap database. In addition, we are currently implementing a laboratory information management system (LIMS) for biospecimen tracking and long-term laboratory data processing and storage of laboratory meta-data.
b. Postnatal: Consistent with our developed protocols and procedures, we also initiated recruitment of birthed infants into P1 in December 2015. To date, we have collected the following number of urine samples from diapers at the various post-birth time points: 87 samples at 1-week, 112 samples at 3-months, 110 samples at 6-months, and 74 samples at 12-months, and 60 samples at 18-months.
2) Exposure and Outcome Characterization:
a. Environmental Toxicants: i. We performed pilot testing of our laboratory methods for analysis of serum toxicants using serum samples collected from women in the same Parent Study Cohort, under a pilot funding award: Serum samples from the first 184 pregnant African American women enrolled in the Prenatal Microbiome Study were analyzed in the Health and Exposome Research Center: Understanding Lifetime Exposures (HERCULES) Analytic Chemistry Core Lab (the Laboratory for Exposure Assessment and Development in Environmental Research (LEADER) directed by Drs. Barr and Ryan) with funds from a HERCULES pilot award made to a junior faculty mentored by PIs Dunlop and Corwin. This chemical toxicant analysis involves a solvent extraction and cleanup with analysis by gas chromatography-tandem mass spectrometry ii. In addition, we have performed quantification of urine phthalates, alkylphenols including bisphenol A (BPA) and bisphenol F (BPF), and cotinine among 169 enrolled pregnant women including N=284 hospital visit 1 samples, N=141 home visit samples and N=164 hospital visit 2 samples for a total of N=388 samples. We found that our population has higher levels of a metabolite of diethylphthalate than does the US population as a whole and US non-Hispanic Black population. Urinary cotinine levels indicate about 30% of our population is actively smoking which is greater than the percentage reporting smoking. We are continuing phthalate, alkylphenol and cotinine analyses in the remainder of the samples we have collected at present and anticipate their completion in June 2020. iii. Through both the LEADER laboratory and through one of the Children’s Health Exposure Analysis Resources funded for Environmental influences on Child Health Outcome (ECHO), we have measured poly- and per-fluoroalkyl substances in all of the CCHEM2 participants at enrollment. iv. We measured persistent organic pollutants including DDT, its degradate DDE, PCBs and PBDEs in the same 284 women. We found higher levels of PBDE congener 47 in our population than in the general US population and DDE levels that were more similar to population-based levels derived over 15 years ago indicating persistently high body burdens of DDE in our population. v. We measured parabens, bisphenol S, current-use pesticides, PAHs, heavy metals and metalloids in N=56 women (hospital visit 1 samples) to determine prevalence and magnitude of exposures in our population. Our data indicate widespread exposure to all of these chemicals with current-use pesticide levels higher than pre-residential ban levels measured 15 years ago in the US population.
Table 1. Selected prenatal urinary and serum toxicant concentrations in the C-CHEM2 study
All | 8-14 wks gestation | 20-24 wks gestation | 24-30 wks gestation | |||||||
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FOD% | N | Median | IQR | N | Median | IQR | N | Median | IQR | |
BPA (ng/mL) | 97 | 284 | 1.07 | 1.49 | 141 | 0.91 | 1.21 | 164 | 0.75 | 1.21 |
MEP (ng/mL)* | 100 | 278 | 94.54 | 177.48 | 139 | 76.83 | 116.10 | 163 | 77.5 | 191.27 |
MEHP (ng/mL) † | 97 | 278 | 1.73 | 3.55 | 139 | 1.71 | 3.01 | 163 | 2.34 | 4.25 |
MEOHP (ng/mL) † | 100 | 278 | 313 | 439 | 139 | 2.78 | 3.48 | 163 | 3.42 | 5.16 |
MEHHP (ng/mL) † | 100 | 278 | 5.09 | 8.80 | 139 | 3.62 | 5.00 | 163 | 4.27 | 6.25 |
MiBP (ng/mL) ‡** | 96 | 278 | 8.83 | 14.35 | 139 | 7.44 | 12.86 | 163 | 8.44 | 12.79 |
MnBP (ng/mL) ‡ | 98 | 278 | 10.30 | 14.88 | 139 | 9.11 | 14.07 | 163 | 9.74 | 19.54 |
MBzP (ng/mL ‡ | 97 | 278 | 6.14 | 11.08 | 139 | 4.15 | 7.82 | 163 | 4.62 | 9.39 |
PFOS (ng/mL) | 100 | 466 | 2.37 | 1.88 | ||||||
PFOA (ng/mL) | 100 | 466 | 0.69 | 0.62 | ||||||
PFNA (ng/mL) | 96 | 466 | 0.26 | 0.28 | ||||||
PFHxS (ng/mL) | 93 | 466 | 1.21 | 0.69 | ||||||
PBDE47 (pg/mL) | 100 | 332 | 81.92 | 81.69 | ||||||
PBDE99 (pg/mL) | 77 | 332 | 12.99 | 27.96 | ||||||
PBDE100 (pg/mL) | 91 | 332 | 14.97 | 27.73 | ||||||
p,p'-DDE (pg/mL) | 100 | 124 | 204.00 | 141.74 | ||||||
HCB (pg/mL) | 98 | 124 | 61.25 | 17.75 | ||||||
FOD = frequency of detection; IQR=interquartile range; *metabolite of diethylphthalate; †=metabolite of diethylhexylphthalate; ‡=metabolite of butylbenzyl phthalate; **metabolite of dibutylphthalate; BPA=bisphenol A; MEP=monoethylphthalate; MEHP=momo-ethylhexyphthalate; MEOHP=momo-(2-ethyl-5oxoheyl) phthalate; MEHHP=mono-(2-ethyl-5-hudroxuhexyl) phthalate; MiBP=mono-isobutyphthalate; MnBP=mono-n-butyphthalate; MBzP=monobenzylphthalate; PFOS=perflurooctanesulfonic acid; PFOA=perflurooctanoic acid; PFNA=perflurononoic acid; PFHxS=perflurohexane sulfonic acid; HCB=hexachlorobenzene |
b. Microbiome: In February 2019 we transferred completely the microbiome swab samples collected on enrolled women to the Emory Integrated Genomics Core for DNA extraction and the extracted DNA samples to the Institute for Genomic Sciences for 16S rRNA gene sequencing. The raw sequencing data was returned to us in late October 2019. The raw sequence files have been processed through an established bioinformatics pipeline that included de-multiplexing using the dual-barcode strategy and then processing following the DADA2 Workflow for Big Data and dada2 (v. 1.5.2) (https://benjjneb.github.io/dada2/bigdata.html). Specifically, forward and reverse reads were trimmed and filtered to contain no ambiguous bases, minimum quality score of 2, and required to contain less than two expected errors based on their quality score. The relationship between quality scores and error rates were estimated for both sequencing runs to reduce batch effects arising from run-to-run variability. Reads were assembled and chimeras for the combined runs removed as per dada2 protocol. Taxonomy was assigned to each amplicon sequence variant (ASV) generated by dada2 using the PECAN (version 1.0), a rapid per sequence classifier (http://ravel-lab.org/pecan). Read counts for ASVs assigned to the same taxonomy were summed for each sample.
c. Pregnancy Outcomes: We have ascertained pregnancy outcomes (via maternal and infant medical record abstraction) for the 318 enrolled pregnant women who have reached their pregnancy due date, with the following birth outcomes noted: 32 fetal deaths (spontaneous abortions or still births); 6 medically-indicated abortions; 39 preterm births; 90 early term births; 147 full term births; and 13 lost-to-follow-up (without delivery outcome records available and unable to contact the participant). The remainder of the women in the cohort are still pregnant and we will ascertain their pregnancy outcomes when their expected delivery date passes.
3) Manuscript Preparation:
Based on our data collected and analyzed to date, we are preparing the following manuscripts: a. Characterizing exposure in an Atlanta-area African America birth cohort – draft circulating b. Concentrations of Urinary Metabolites of Phthalates in an Atlanta-area African American Birth Cohort – student working on draft for thesis c. Concentrations of Serum PBDE’s in an Atlanta-area African American Birth Cohort d. Concentrations of Alkylated Environmental Phenols in an Atlanta-area African American Birth Cohort
4) To date, data collected from our study have supported six MPH theses and one PhD dissertation: a. Feminine Hygiene products: A possible source of exposure among pregnant African American women in Atlanta, GA. Gursharan Claire. b. An Analysis of the Effects of Marijuana Use upon Maternal Phthalate Exposure. Natalie Duke. c. Predictors of PBDE exposure in an Atlanta-area birth cohort: The CHERUB study – Yitong Guo d. Predictors of tobacco smoke exposure in an Atlanta-area birth cohort – Victoria Davidson e. Predictors and pregnancy outcomes of BPA in an Atlanta-area birth cohort – Tassia Drame f. Predictors of phthalate exposure in an Atlanta-area birth cohort – Theresa Williams g. Predictors of organophosphate flame retardant exposure and birth outcomes in an Atlanta-area birth cohort – Che-Rong Chang
5) We have interfaced with representatives from the COTC and the Community Advisory Board to discuss strategies for displaying individual- and group-level data and providing feedback about environmental exposures to participants and community members.
Future Activities:
During the next reporting period, we will carry out the activities designated in our Timeline for NCE Year 5. Specifically, together with our trained staff and established protocols, we will continue to recruit and enroll pregnant women and birthed infants into P1, collect relevant data and specimens to allow us to characterize environmental toxicant exposures, continue to analyze data and samples to allow us to characterize environmental exposures in the population of interest and discern the relationship between environmental exposures, the microbiome, and adverse pregnancy and neurodevelopmental outcomes, and develop and disseminate our research findings via manuscripts and scientific presentations. In addition, we will continue to engage with the Stakeholder Advisory Board to solicit their input into how we should disseminate findings to the African American community and clinical and public health care providers for this community.
Journal Articles: 28 Displayed | Download in RIS Format
Other center views: | All 76 publications | 30 publications in selected types | All 28 journal articles |
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Chang C, Barr D, Zhang Q, Dunlop A, Smarr M, Kannan K, Panuwet P, Tangpricha V, Shi L, Liang D, Corwin E, Ryan P. Associations of single and multiple per-and polyfluoroalkyl substance PFAS exposure with vitamin D biomarkers in African American women during pregnancy. ENVIRONMENTAL RESEARCH 2021;202(111713). |
R836153 (Final) |
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Chang C, Ryan P, Smarr M, Kannan K, Panuwet P, Dunlop A, Corwin E, Barr D. Serum per-and polyfluoroalkyl substance PFAS concentrations and predictors of exposure among pregnant African American women in the Atlanta area, Georgia. ENVIRONMENTAL RESEARCH 2021;198(110445). |
R836153 (Final) |
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Corwin EJ, Hogue CJ, Pearce B, Hill CC, Read TD, Mulle J, Dunlop AL. Protocol for the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Cohort Study. BMC Pregnancy and Childbirth 2017;17(1):161 (8 pp.). |
R836153 (2018) |
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Eatman J, Dunlop A, Barr D, Corwin E, Hill C, Brennan P, Ryan P, Panuwet P, Taibl K, Tan Y, Liang D, Eik S. Exposure to phthalate metabolites, bisphenol A, and psychosocial stress mixtures and pregnancy outcomes in the Atlanta African American maternal-child cohort. ENVIRONMENTAL RESEARCH 2023;233(116464) |
R836153 (Final) |
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Edwards SM, Cunningham SA, Dunlop AL, Corwin EJ. The maternal gut microbiome during pregnancy. MCN: The American Journal of Maternal/Child Nursing 2017;42(6):310-317. |
R836153 (2018) R836153 (2019) |
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Eick S, Tan Y, Taibl K, Ryan P, Barr D, Huls A, Eatman J, Panuwet P, D'Souza P, Yakimavets V, Lee G, Brennan P, Corwin E, Dunlop A, Liang D. Prenatal exposure to persistent and non-persistent chemical mixtures and associations with adverse birth outcomes in the Atlanta African American Maternal-Child Cohort. JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMMIOLOGY 2023;Early Access |
R836153 (Final) |
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Eick S, Barr D, Brennan P, Taibl K, Tan Y, Robinson M, Kannan K, Panuwet P, Yakimavets V, Ryan P, Liang D, Dunlop A. Per-and polyfluoroalkyl substances and psychosocial stressors have a joint effect on adverse pregnancy outcomes in the Atlanta African American Maternal-Child cohort. SCIENCE OF THE TOTAL ENVIRONMENT 2023;857(2):159450. |
R836153 (Final) |
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Frediani JK, Naioti EA, Vos MB, Figueroa J, Marsit CJ, Welsh JA. Arsenic exposure and risk of nonalcoholic fatty liver disease (NAFLD) among U.S. adolescents and adults: an association modified by race/ethnicity, NHANES 2005-2014. Environmental Health 2018;17(1):6 (8 pp.). |
R836153 (2018) R835442 (2018) |
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Gardinassi LG, Xia J, Safo SE, Li S. Bioinformatics tools for the interpretation of metabolomics data. Current Pharmacology Reports 2017;3(6):374-383. |
R836153 (2018) |
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Gardinassi LG, Cordy RJ, Lacerda MVG, Salinas JL, Monteiro WM, Melo GC, Siqueira AM, Val FF, Tran V, Jones DP, Galinski MR, Li S. Metabolome-wide association study of peripheral parasitemia in Plasmodium vivax malaria. International Journal of Medical Microbiology 2017;307(8):533-541. |
R836153 (2018) |
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Kartavenka K, Panuwet P, Yakimavets V, Jaikang C, Thipubon K, D'Souza P, Barr D, Ryan P. LC-MS Quantification of Malondialdehyde-Dansylhydrazine Derivatives in Urine and Serum Samples. JOURNAL OF ANALYTICAL TOXICOLOGY 2020;44(5):470-481. |
R836153 (Final) |
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Li S, Dunlop AL, Jones DP, Corwin EJ. High-resolution metabolomics: review of the field and implications for nursing science and the study of preterm birth. Biological Research for Nursing 2016;18(1):12-22. |
R836153C001 (2016) R836153C003 (2016) R836153C003 (2017) |
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Mutic AD, Baker BJ, McCauley LA. Deleterious effects from occupational exposure to ethylene thiourea in pregnant women. Workplace Health and Safety 2017;65(12):595-602. |
R836153 (2018) |
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Mutic AD, Jordan S, Edwards SM, Ferranti EP, Thul TA, Yang I. The postpartum maternal and newborn microbiomes. MCN: The American Journal of Maternal/Child Nursing 2017;42(6):326-331. |
R836153 (2018) |
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Rodriguez J, Huntington-Moskos L, Johnson A, Williams S, Gulledge E, Feeley C, Rice M. Collecting biological measures for research with children and adolescents. Journal of Pediatric Health Care 2016;30(3):279-283. |
R836153C002 (2016) |
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Rodriguez J, Jordan S, Mutic A, Thul T. The neonatal microbiome: implications for neonatal intensive care unit nurses. MCN: The American Journal of Maternal/Child Nursing 2017;42(6):332-337. |
R836153 (2018) |
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Runkle J, Flocks J, Economos J, Dunlop AL. A systematic review of Mancozeb as a reproductive and developmental hazard. Environment International 2017; 99:29-42. |
R836153 (2018) R836153 (2019) |
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Swales DA, Winiarski DA, Smith AK, Stowe ZN, Newport DJ, Brennan PA. Maternal depression and cortisol in pregnancy predict offspring emotional reactivity in the preschool period. Developmental Psychobiology 2018;60(5):557-566. |
R836153 (2018) |
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Talibl K, Dunlop A, Barr D, Ryan P, Panuwet P, Corwin E, Eatman J, Tan Y, Liang D, Eick S. Phthalate exposure increases interferon-γ during pregnancy: The Atlanta African American Maternal-Child Cohort. SCIENCE OF THE TOTAL ENVIRONMENT 2024;916(170344) |
R836153 (Final) |
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Tchen R, Tan Y, Barr D, Ryan P, Tran V, Li Z, Hu Y, Smith A, Jones D, Dunlop A. Use of high-resolution metabolomics to assess the biological perturbations associated with maternal exposure to Bisphenol A and Bisphenol F among pregnant African American women. ENVIRONMENTAL INTERNATIONAL 2022;169(107530). |
R836153 (Final) |
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Yakimavets V, Qiu T, Panuwet P, D'Souza P, Brennan P, Dunlop A, Ryan P, Barr D. Simultaneous quantification of urinary tobacco and marijuana metabolites using solid-supported liquid-liquid extraction coupled with liquid chromatography tandem mass spectrometry. JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES 2022;1208(123378). |
R836153 (Final) |
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Zhang Z, Barr D, Dunlop A, Panuwet P, Sarnat J, Lee G, Tan Y, Corwin E, Jones D, Ryan P, Liang D. Assessment of metabolic perturbations associated with exposure to phthalates among pregnant African American women. SCIENCE OF THE TOTAL ENVIRONMENT 2022;818(151689). |
R836153 (Final) |
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Dunlop AL, Knight AK, Satten GA, Cutler AJ, Wright ML, Mitchell RM, Read TD, Mulle J, Hertzberg VS, Hill CC, Smith AK. Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women:the effect of socioeconomic status and antibiotic exposure. PeerJ 2019;7:e8004. |
R836153 (2019) |
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Dunlop AL, Jordan SL, Ferranti EP, Hill CC, Patel S, Hao L, Corwin EJ, Tangpricha V. Total and Free 25-Hydroxy-Vitamin D and Bacterial Vaginosis in Pregnant African American Women. Infectious diseases in obstetrics and gynecology. 2019;2019. |
R836153 (2019) |
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Jordan, S., Baker, B., Dunn, A., Edwards, S., Ferranti, E. Mutic, A., Yang, I., & Rodriguez, J. (2017). Maternal‐child microbiome:Collection, storage, and implications for research and practice. Nursing Research, 66(2), 175‐183. |
R836153 (2017) R836153C002 (2017) |
not available |
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Rodriguez, J., Huntington-Moskos, L., Johnson, A., Williams, S., Gulledge, E., Feeley, C., & Rice, M. (2016). Collecting biological measures for research with children and adolescents. Journal of Pediatric Health Care, Doi 10.1016/j.pedhc.2015.12.007. |
R836153C002 (2017) |
not available |
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Rodriguez, J., Jordan, S., Mutic, A., & Thul, T. The neonatal microbiome:Implications for the NICU nurse. MCN:The American Journal of Maternal/Child Nursing. (in press). |
R836153 (2017) |
not available |
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Mutic, A., Jordan, S., Ferranti, E., Thul, T., Edwards, S., Yang, I. (2017). The Postpartum and Newborn Microbiomes. MCN; The American Journal of Maternal/Child Nursing. (in press). |
R836153 (2017) R836153C002 (2017) |
not available |
Supplemental Keywords:
Chemical exposure, early life exposure, environmental exposure, infant developmentProgress and Final Reports:
Original Abstract Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836153C001 Characterizing Exposures and Outcomes in an Urban Birth Cohort (CHERUB)
R836153C002 Microbiome, Environment, and Neurodevelopmental Delay (MEND)
R836153C003 Metabolic, Microbiome and Toxicant-Related Interactions (MATRIX)
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.