Early genistein exposure of California mice and effects on the gut microbiota–brain axis

in Journal of Endocrinology
Authors:
Brittney L Marshall Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
Biomedical Sciences, University of Missouri, Columbia, Missouri, USA

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Yang Liu Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
Informatics Institute, University of Missouri, Columbia, Missouri, USA

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Michelle J Farrington Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
Biomedical Sciences, University of Missouri, Columbia, Missouri, USA

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Jiude Mao Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
Biomedical Sciences, University of Missouri, Columbia, Missouri, USA

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William G Helferich Food Science and Human Nutrition, University of Illinois, Urbana, Illinois, USA

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A Katrin Schenk Physics, Randolph College, Lynchburg, Virginia, USA

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Nathan J Bivens DNA Core Facility, University of Missouri, Columbia, Missouri, USA

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Saurav J Sarma Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
MU Metabolomics Center, University of Missouri, Columbia, Missouri, USA

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Zhentian Lei Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
MU Metabolomics Center, University of Missouri, Columbia, Missouri, USA
Department of Biochemistry, University of Missouri, Columbia, Missouri, USA

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Lloyd W Sumner Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
MU Metabolomics Center, University of Missouri, Columbia, Missouri, USA
Department of Biochemistry, University of Missouri, Columbia, Missouri, USA

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Trupti Joshi Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
Informatics Institute, University of Missouri, Columbia, Missouri, USA
Department of Health Management and Informatics, School of Medicine, University of Missouri, Columbia, Missouri, USA

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Cheryl S Rosenfeld Bond Life Sciences Center, University of Missouri, Columbia, Missouri, USA
Biomedical Sciences, University of Missouri, Columbia, Missouri, USA
Informatics Institute, University of Missouri, Columbia, Missouri, USA
Thompson Center for Autism and Neurobehavioral Disorders, University of Missouri, Columbia, Missouri, USA
Genetics Area Program, University of Missouri, Columbia, Missouri, USA

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Correspondence should be addressed to C S Rosenfeld: rosenfeldc@missouri.edu
DOI:
https://doi.org/10.1530/JOE-19-0214
Volume/Issue:
Volume 242: Issue 2
Article Type:
Research Article
Page Range:
139–157
Online Publication Date:
Aug 2019
Copyright:
© 2019 Society for Endocrinology 2019
Restricted access
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Human offspring encounter high amounts of phytoestrogens, such as genistein (GEN), through maternal diet and soy-based formulas. Such chemicals can exert estrogenic activity and thereby disrupt neurobehavioral programming. Besides inducing direct host effects, GEN might cause gut dysbiosis and alter gut metabolites. To determine whether exposure to GEN affects these parameters, California mice (Peromyscus californicus) dams were placed 2 weeks prior to breeding and throughout gestation and lactation on a diet supplemented with GEN (250 mg/kg feed weight) or AIN93G phytoestrogen-free control diet (AIN). At weaning, offspring socio-communicative behaviors, gut microbiota and metabolite profiles were assayed. Exposure of offspring to GEN-induced sex-dependent changes in gut microbiota and metabolites. GEN exposed females were less likely to investigate a novel female mouse when tested in a three-chamber social test. When isolated, GEN males and females exhibited increased latency to elicit their first call, suggestive of reduced motivation to communicate with other individuals. Correlation analyses revealed interactions between GEN-induced microbiome, metabolome and socio-communicative behaviors. Comparison of GEN males with AIN males revealed the fraction of calls above 20 kHz was associated with daidzein, α-tocopherol, Flexispira spp. and Odoribacter spp. Results suggest early GEN exposure disrupts normal socio-communicative behaviors in California mice, which are otherwise evident in these social rodents. Such effects may be due to GEN disruptions on neural programming but might also be attributed to GEN-induced microbiota shifts and resultant changes in gut metabolites. Findings indicate cause for concern that perinatal exposure to GEN may detrimentally affect the offspring microbiome–gut–brain axis.

Supplementary Materials

    • Supplementary Figures 1. Key for the bacterial species listed in Figure 1.
    • Supplementary Figures 2. Key for the bacterial species listed in Figure 1.
    • Supplementary Figure 3. Key for the bacterial species listed in Figure 1.
    • Supplementary Figure 4. Key for the bacterial species listed in Figure 1.
    • Supplementary Figure 5. Venn diagram showing number of overlap and unique metabolites that were significantly regulated in each comparison based on treatment X sex interactions.
    • Supplementary Figure 6. Pathway maps of methionine and glutamate metabolism. Pathway maps of A) methionine and B) glutamate metabolism, which are the most significant pathways associated F-GEN vs. F-AIN individuals, as identified in the pathway analysis in Figure 8. Compounds in light blue color are not included in the list of significant metabolites, and the ones with a red circle are altered by GEN-exposure.
    • Supplementary Figure 7. Correlation across microbiome, metabolites, social and vocal behavior at component of F-GEN vs. F-AIN individuals, cutoff = 0.9.
    • Supplementary Figure 8. Correlation across microbiome, metabolites, social and vocal behavior at component of M-GEN vs. M-AIN individuals, cutoff = 0.9.
    • Supplementary Figure 9. Correlation across microbiome, metabolites, social and vocal behavior at component of M-GEN vs. F-GEN individuals, cutoff = 0.9.
    • Supplementary Figure 10. Correlation across microbiome, metabolites, social and vocal behavior at component of M-AIN vs. F-AIN individuals, cutoff = 0.9.
    • Supplementary File 1. List of bacteria that differ between GEN females and AIN females.
    • Supplementary File 2. List of bacteria that differ between GEN males and AIN males.
    • Supplementary File 3. List of detected components. The MS data were deconvoluted by using AMDIS to yield a total of 528 components.
    • Supplementary File 4. List of identified components. The MS data were deconvoluted by using AMDIS and annotated by searching against our custom in-house and NIST17 MS spectral libraries.
    • Supplementary File 5. List of significantly changed metabolites. The significant metabolites were determined using a volcano plot that combines fold change (FC>2) and t-test (p < 0.05).
    • Supplementary File 6. Correlations of Circos plots associated with M-GEN vs. F-GEN groups, M-AIN vs. F-AIN groups, M-GEN vs. M-AIN, and F-GEN vs. F-AIN.

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Print ISSN:
0022-0795
Online ISSN:
1479-6805
Copyright:
© 2019 Society for Endocrinology 2019
Page(s):
19
Article Type:
Research Article
Received Date:
31 May 2019
Accepted Date:
10 Jun 2019
Print Publication Date:
01 Aug 2019
Online Publication Date:
Aug 2019
Keywords:
phytoestrogens; brain; intestinal bacteria; diet; xenoestrogens; rodent models; bioinformatics; autism; ASD