The Microbiota-Gut-Brain Axis and Postpartum Depression

微生物群-肠-脑轴和产后抑郁症

• 批准号: 9765403
• 负责人: Mary Claire Kimmel
• 金额: $ 19.88万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765403
• 关键词: 16S ribosomal RNA sequencing; Academic Training; Adrenal Cortex Hormones; Advocate; Affect; Affective; Anhedonia; Animal Experimentation; Animals; Anti-inflammatory; Anxiety; Anxiety Disorders; Area; Area Under Curve; Arousal; Bacteria; Basic Science; Behavior; Biological; Brain; Child; Clinical; Clinical Research; Cognitive; Complement; Data; Development; Diagnosis; First Pregnancy Trimester; Foundations; Funding; Future; Glucocorticoids; Goals; Gonadal Steroid Hormones; Human; Hydrocortisone; Individual; Individual Differences; Infant; Infanticide; Inflammatory; Intervention; Interview; Intestines; Joints; Knowledge; Kynurenine; Life; Major Depressive Disorder; Measures; Mental Depression; Mental Health; Metabolic; Metabolic Pathway; Metabolism; Metagenomics; Moods; Morbidity - disease rate; Mothers; Neopterin; Organism; Outcome; Pathological anxiety; Perinatal; Phenotype; Plasma; Population; Postpartum Depression; Postpartum Period; Pregnancy; Prevention; Process; Psychiatry; Recording of previous events; Reporting; Research; Research Personnel; Research Training; Risk; Role; Sampling; Scientist; Serotonergic System; Serotonin; Serum; Stress; Testing; Third Pregnancy Trimester; Training; Translating; Translational Research; Trier Social Stress Test; Tryptophan; Variant; Woman; Work; anxious; anxious behavior; career; career development; clinical development; clinically significant; comparative; depressive behavior; depressive symptoms; gut bacteria; gut microbiome; gut microbiota; ideation; improved; improved outcome; in utero; individualized medicine; maternal microbiota; microbial; microbiome; microbiome research; microbiota; microbiota-gut-brain axis; mortality; neurotransmitter metabolism; novel; perinatal period; perinatal women; personalized intervention; personalized medicine; recruit; skills; societal costs; stress reactivity; suicidal; tetrahydrobiopterin; translational scientist

Abstract Postpartum depression (PPD), a subtype of MDD, has significant morbidity and mortality for mother and child, but current options for prevention, diagnosis and treatment are limited. An emerging area of research in mental health is the study of the gut microbiota. The microbiota-gut-brain axis in relation to PPD is a novel area of research. Animal research suggests specific groups of pro-inflammatory bacteria are associated with anxious and depressive behaviors while specific groups of anti-inflammatory bacteria are associated with decreased anxious and depressive behaviors. Animal studies also indicate that microbial variation is associated with changes in HPA stress reactivity and changes in serotonin (5-HT) metabolism. We propose translating these findings to a clinical study of perinatal women. We will use 16S rRNA sequencing to identify changes in microbial composition over the course of pregnancy in order to 1) determine if women who develop increased pro-inflammatory bacteria and decreased anti-inflammatory bacteria across pregnancy are more likely to develop PPD; 2) determine if perinatal alterations in gut microbiota affect postpartum stress reactivity; and 3) determine how perinatal alterations in gut microbiota associate with changes in 5-HT metabolism. This research will support my primary career goal to become an independently funded clinical scientist with the expertise necessary to conduct state-of-the-art mechanistic research of the microbiota-gut-brain axis and PPD. My long-term research objectives are to: 1) advance our understanding of the microbiota-gut-brain axis changes during perinatal period in relation to PPD; 2) continue to examine the mechanistic underpinnings of PPD with regards to increased stress reactivity and altered 5-HT system and neurotransmitter metabolism; 3) identify women at risk of developing PPD and to apply the knowledge gained from maternal studies to understand the impact of the maternal microbiota-gut-brain axis on the infant beginning in utero through the first year of life; and 4) translate what is learned to develop and advocate for individualized treatments for the mother-infant dyad utilizing the microbiota-gut-brain axis. The specific objectives to meet my career goal are to 1) become knowledgeable and adept in comparative metagenomics; 2) improve my capability to study component affective processes of PPD; 3) become skilled in assessing stress reactivity; 4) gain understanding of and to become dexterous at studying the 5-HT system and neurotransmitter metabolism; 5) obtain expertise in developing translational research that can integrate mechanistic findings from basic science to clinical research of perinatal populations and to generate pilot data that will be the foundation for future work. Future directions will include studying the joint effects of the perinatal microbiota changes and PPD on the infant microbiota, mother-infant interactions and infant cognitive outcomes in order to develop interventions to improve outcomes for mother and child. This career development application represents the critical next step in my academic and research training and to improved understanding of the microbiota-gut-brain axis and PPD.

抽象的 MDD的亚型产后抑郁症（PPD）对母亲和儿童具有显着的发病率和死亡率， 但是当前的预防，诊断和治疗方案是有限的。一个新兴研究领域 心理健康是肠道菌群的研究。与PPD相关的微生物群 - 脑轴是一种新颖 研究领域。动物研究表明，特定的促炎细菌组与 焦虑和抑郁行为，而特定的抗炎细菌组与 减少焦虑和抑郁行为。动物研究还表明，微生物的变异是 与HPA应激反应性的变化以及5-羟色胺（5-HT）代谢的变化有关。我们建议 将这些发现转化为围产期妇女的临床研究。我们将使用16S rRNA测序来识别 在整个怀孕过程中，微生物组成的变化以至1）确定是否发展 促炎细菌增加和整个怀孕的抗炎细菌减少更多 可能发展PPD； 2）确定肠道菌群的围产期改变是否会影响产后应激反应性； 3）确定肠道微生物群的围产期改变如何与5-HT代谢的变化相关。 这项研究将支持我的主要职业目标，成为成为独立资助的临床科学家 对微生物核脑轴和PPD进行最先进的机械研究所需的专业知识。 我的长期研究目标是：1）提高我们对微生物统一轴的理解 与PPD有关的围产期时期的变化； 2）继续检查 PPD关于增加的压力反应性，改变了5-HT系统和神经递质代谢； 3） 确定有发展PPD的风险的妇女，并将从母体研究中获得的知识应用于 了解孕产妇微生物群 - 脑轴对从子宫开始的婴儿的影响 生命的第一年； 4）翻译知识的东西以开发和倡导个性化治疗 使用微生物核脑轴的母二元组。实现我职业目标的具体目标是 1）知识渊博并擅长于比较宏基因组学； 2）提高我学习的能力 PPD的组成情感过程； 3）熟练评估压力反应性； 4）获得理解 在研究5-HT系统和神经递质代谢方面变得灵巧； 5）获得专业知识 在开发可以整合从基础科学到临床的机理发现的转化研究 对围产期人群的研究并生成试点数据，这将成为未来工作的基础。 未来的方向将包括研究围产期菌群变化的关节作用和PPD对 婴儿菌群，母亲相互作用和婴儿认知结果，以开发干预措施 改善母子的结果。该职业发展应用程序代表了下一步的关键 我的学术和研究培训，并提高对微生物群 - 脑轴和PPD的了解。

项目成果

Emerging literature in the Microbiota-Brain Axis and Perinatal Mood and Anxiety Disorders.

• DOI: 10.1016/j.psyneuen.2018.05.020
• 发表时间: 2018-09
• 期刊: Psychoneuroendocrinology
• 影响因子: 3.7
• 作者: Rackers HS;Thomas S;Williamson K;Posey R;Kimmel MC
• 通讯作者: Kimmel MC

The microbiota-gut-brain axis and perceived stress in the perinatal period.

• DOI: 10.1007/s00737-023-01300-9
• 发表时间: 2023-04
• 期刊: Archives of women's mental health

Heart rate variability in late pregnancy: exploration of distinctive patterns in relation to maternal mental health.

• DOI: 10.1038/s41398-021-01401-y
• 发表时间: 2021-05-14
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Kimmel MC;Fransson E;Cunningham JL;Brann E;Grewen K;Boschiero D;Chrousos GP;Meltzer-Brody S;Skalkidou A
• 通讯作者: Skalkidou A