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      Maternal precarity and HPA axis functioning shape infant gut microbiota and HPA axis development in humans

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          Abstract

          Background

          Early life exposure to adverse environments, and maternal stress in particular, has been shown to increase risk for metabolic diseases and neurobehavioral disorders. While many studies have examined the hypothalamic-pituitary-adrenal axis (HPA axis) as the primary mechanism behind these relationships, emerging research on the brain-gut axis suggests that the microbiome may play a role. In this study, we tested the relationships among maternal precarity and HPA axis dysregulation during the peripartum period, infant gut microbiome composition, and infant HPA axis functioning.

          Methods

          Data come from 25 mother-infant dyads in the Galápagos, Ecuador. Women completed surveys on precarity measures (food insecurity, low social support, depression, and stress) and gave salivary cortisol samples during and after pregnancy. Infant salivary cortisol and stool were collected in the postpartum. Statistical significance of differences in microbial diversity and relative abundance were assessed with respect to adjusted linear regression models.

          Results

          Maternal precarity was associated with lower diversity and higher relative abundance of Enterobacteriaceae and Streptococcaceae and a lower relative abundance of Bifidobacterium and Lachnospiraceae. These patterns of colonization for Enterobacteriaceae and Bifidobacterium mirrored those found in infants with HPA axis dysregulation. Maternal HPA axis dysregulation during pregnancy was also associated with a greater relative abundance of Veillonella.

          Conclusions

          Overall, exposures to precarity and HPA axis dysregulation were associated with an increase in groups that include potentially pathogenic bacteria, including Enterobacteriaceae, Streptococcaceae, and Veillonella, and a decrease in potentially protective bacteria, including Bifidobacterium and Lachnospiraceae, as well as a decrease in overall diversity.

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          Most cited references88

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          The PHQ-9: validity of a brief depression severity measure.

          While considerable attention has focused on improving the detection of depression, assessment of severity is also important in guiding treatment decisions. Therefore, we examined the validity of a brief, new measure of depression severity. The Patient Health Questionnaire (PHQ) is a self-administered version of the PRIME-MD diagnostic instrument for common mental disorders. The PHQ-9 is the depression module, which scores each of the 9 DSM-IV criteria as "0" (not at all) to "3" (nearly every day). The PHQ-9 was completed by 6,000 patients in 8 primary care clinics and 7 obstetrics-gynecology clinics. Construct validity was assessed using the 20-item Short-Form General Health Survey, self-reported sick days and clinic visits, and symptom-related difficulty. Criterion validity was assessed against an independent structured mental health professional (MHP) interview in a sample of 580 patients. As PHQ-9 depression severity increased, there was a substantial decrease in functional status on all 6 SF-20 subscales. Also, symptom-related difficulty, sick days, and health care utilization increased. Using the MHP reinterview as the criterion standard, a PHQ-9 score > or =10 had a sensitivity of 88% and a specificity of 88% for major depression. PHQ-9 scores of 5, 10, 15, and 20 represented mild, moderate, moderately severe, and severe depression, respectively. Results were similar in the primary care and obstetrics-gynecology samples. In addition to making criteria-based diagnoses of depressive disorders, the PHQ-9 is also a reliable and valid measure of depression severity. These characteristics plus its brevity make the PHQ-9 a useful clinical and research tool.
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            Reproducible, interactive, scalable and extensible microbiome data science using QIIME 2

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              Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness

              Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: VisualizationRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: MethodologyRole: SoftwareRole: Writing – review & editing
                Role: ConceptualizationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 May 2021
                2021
                : 16
                : 5
                : e0251782
                Affiliations
                [1 ] Department of Anthropology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
                [2 ] Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
                [3 ] Research Computing Center, University of North Carolina, Chapel Hill, Chapel Hill, North Carolina, United States of America
                [4 ] UNC Microbiome Core, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
                [5 ] Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina, United States of America
                [6 ] Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America
                University of Illinois at Urbana-Champaign, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                https://orcid.org/0000-0003-1875-5332
                Article
                PONE-D-20-17822
                10.1371/journal.pone.0251782
                8136730
                34015045
                9c60d230-bcc7-4986-ab7f-9391c8ebef18
                © 2021 Jahnke et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 11 June 2020
                : 3 May 2021
                Page count
                Figures: 5, Tables: 4, Pages: 24
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100008982, National Science Foundation;
                Award ID: BCS-1730297
                Award Recipient :
                Funded by: Fulbright-Hays Program
                Award ID: P022A170061
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100009633, Eunice Kennedy Shriver National Institute of Child Health and Human Development;
                Award ID: T32-HD007168
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100013506, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill;
                Award ID: P30 DK034987
                Funded by: funder-id http://dx.doi.org/10.13039/100011073, Nutrition Obesity Research Center, University of North Carolina;
                Award ID: P30 DK056350
                This work was supported by the National Science Foundation (BCS-1730297) ( https://www.nsf.gov/), The Fulbright-Hays Program(P022A170061) ( https://us.fulbrightonline.org/), the National Institutes ofHealth Eunice Kennedy Shriver National Institute of Child Health and HumanDevelopment Training Grant (T32-HD007168) through the Carolina PopulationCenter ( https://www.cpc.unc.edu/), the Center for Gastrointestinal Biology and Disease at the School of Medicine at the University of North Carolina (P30 DK034987), and the Nutrition Obesity Research Center at the University of North Carolina (P30 DK056350). The funders had no role in study design, data collection, data analysis, data interpretation, writing, or publication submission decision-making.
                Categories
                Research Article
                Medicine and Health Sciences
                Women's Health
                Maternal Health
                Pregnancy
                Medicine and Health Sciences
                Women's Health
                Obstetrics and Gynecology
                Pregnancy
                People and Places
                Population Groupings
                Age Groups
                Children
                Infants
                People and Places
                Population Groupings
                Families
                Children
                Infants
                Biology and Life Sciences
                Biochemistry
                Hormones
                Lipid Hormones
                Cortisol
                Biology and Life Sciences
                Biochemistry
                Hormones
                Steroid Hormones
                Cortisol
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                Microbiology
                Medical Microbiology
                Microbiome
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                Genomics
                Microbial Genomics
                Microbiome
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                Microbiology
                Microbial Genomics
                Microbiome
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                Bacteria
                Gut Bacteria
                Bifidobacterium
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                Gut Bacteria
                Biology and Life Sciences
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                Enterobacteriaceae
                Biology and Life Sciences
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                Streptococcus
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                Microbiology
                Medical Microbiology
                Microbial Pathogens
                Bacterial Pathogens
                Streptococcus
                Medicine and Health Sciences
                Pathology and Laboratory Medicine
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