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 产后抑郁症 (PPD) 是 MDD 的一种亚型，对母亲和儿童具有显着的发病率和死亡率， 但目前的预防、诊断和治疗选择有限。一个新兴的研究领域 心理健康是对肠道微生物群的研究。与 PPD 相关的微生物群-肠-脑轴是一种新颖的机制 研究领域。动物研究表明特定的促炎细菌群与 焦虑和抑郁行为，而特定组的抗炎细菌与 减少焦虑和抑郁行为。动物研究还表明微生物变异 与 HPA 应激反应性的变化和血清素 (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测序来鉴定 怀孕期间微生物组成的变化，以便 1) 确定女性是否会出现以下情况： 整个怀孕期间促炎细菌增加和抗炎细菌减少更多 可能患上产后抑郁症（PPD）； 2) 确定围产期肠道微生物群的变化是否影响产后应激反应性； 3) 确定围产期肠道微生物群的变化如何与 5-HT 代谢的变化相关。 这项研究将支持我的主要职业目标，成为一名独立资助的临床科学家， 对微生物群-肠-脑轴和 PPD 进行最先进的机制研究所需的专业知识。 我的长期研究目标是：1）增进我们对微生物群-肠-脑轴的理解 围产期与 PPD 相关的变化； 2）继续研究其机制基础 PPD 涉及应激反应性增加以及 5-HT 系统和神经递质代谢的改变； 3） 识别有患产后抑郁症风险的女性，并将从孕产妇研究中获得的知识应用于 了解母体微生物群-肠-脑轴对从子宫内开始的婴儿的影响 生命的第一年； 4）转化所学到的知识来开发和倡导个体化治疗 利用微生物群-肠-脑轴的母婴二元体。实现我的职业目标的具体目标是 1）精通比较宏基因组学； 2）提高我的学习能力 PPD 的情感过程组成部分； 3）熟练评估应激反应性； 4）获得理解 能够熟练地研究 5-HT 系统和神经递质代谢； 5）获得专业知识 开发可将基础科学的机制发现整合到临床的转化研究 对围产期人群进行研究并生成试点数据，为未来工作奠定基础。 未来的方向将包括研究围产期微生物群变化和 PPD 对胎儿的联合影响。 婴儿微生物群、母婴互动和婴儿认知结果，以便制定干预措施 改善母亲和孩子的结局。该职业发展应用程序代表了关键的下一步 我接受了学术和研究培训，并提高了对微生物群-肠-脑轴和 PPD 的理解。

项目成果

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

妊娠晚期心率变异性：探索与孕产妇心理健康相关的独特模式。

• 发表时间: 2021-05-14
• 影响因子: 6.8
• 作者: Kimmel, Mary C;Fransson, Emma;Cunningham, Janet L;Brann, Emma;Grewen, Karen;Boschiero, Dario;Chrousos, George P;Meltzer;Skalkidou, Alkistis
• 通讯作者: Skalkidou, Alkistis

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

微生物群-脑轴以及围产期情绪和焦虑症的新兴文献。

• 发表时间: 2018-09
• 影响因子: 3.7
• 作者: Rackers, Hannah S;Thomas, Stephanie;Williamson, Kelsey;Posey, Rachael;Kimmel, Mary C
• 通讯作者: Kimmel, Mary C

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

微生物群-肠-脑轴和围产期的压力感知。

• 发表时间: 2023-04
• 作者: Long, Emily S;Penalver Bernabe, Beatriz;Xia, Kai;Azcarate;Carroll, Ian M;Rackers, Hannah S;Grewen, Karen M;Meltzer;Kimmel, Mary C
• 通讯作者: Kimmel, Mary C

Metabolite trajectories across the perinatal period and mental health: A preliminary study of tryptophan-related metabolites, bile acids and microbial composition.

围产期代谢轨迹和心理健康：色氨酸相关代谢物、胆汁酸和微生物组成的初步研究。

• 发表时间: 2022-02-10
• 影响因子: 2.7
• 作者: Kimmel, Mary;Jin, Wanting;Xia, Kai;Lun, Kun;Azcarate;Plantinga, Anna;Wu, Michael;Ataei, Shirin;Rackers, Hannah;Carroll, Ian;Meltzer;Fransson, Emma;Knickmeyer, Rebecca
• 通讯作者: Knickmeyer, Rebecca