The Association Between Gut Microbiota Diversity and Postpartum Depression

The Association Between Gut Microbiota Diversity and Postpartum Depression： A Prospective Pilot Study

This study aims to examine whether naturally occurring bacteria in the gastrointestinal tract are associated with mood changes following childbirth, including postpartum depression. Biological samples will be collected before and after delivery to determine whether specific patterns in gut bacterial composition are linked to emotional states. The purpose of the research is to improve understanding of whether such microbial changes can help identify individuals at higher risk for postpartum depression, enabling earlier recognition and intervention.

Study Overview

• Status: Recruiting
• Conditions: Depression During Pregnancy

Detailed Description

This prospective observational pilot study is designed to explore the relationship between gut microbial diversity and depressive symptoms during the early postpartum period. Postpartum depression is one of the most frequent complications after childbirth and has a substantial impact on the physical and psychological well-being of mothers and infants. The study investigates whether differences in gut microbial composition are associated with the development of depressive symptoms following childbirth.

Pregnant individuals aged eighteen years or older planning cesarean delivery at Massachusetts General Hospital will be enrolled. Data and biological samples will be collected at two time points: within three days before delivery and within 2 days after delivery. Blood samples will be collected for measurement of inflammatory markers, and rectal swab samples will be obtained to evaluate the composition and diversity of gut microorganisms through metagenomic sequencing. A validated questionnaire assessing emotional state will be administered at the same time points, and a follow-up emotional assessment will be obtained six weeks after childbirth through the electronic medical record system.

The study examines microbial characteristics associated with the presence or absence of depressive symptoms and evaluates correlations between microbial community patterns and emotional status, aiming to identify potential microbiome-based biomarkers predictive of early onset depressive symptoms after childbirth. The research does not include drug administration, device testing, or experimental treatment. All procedures are non-invasive or minimally invasive and coincide with routine obstetric care, minimizing participant burden.

The results of this study are expected to provide preliminary evidence linking the gut microbial environment to maternal mental health. Findings may inform future strategies for early detection and prevention of postpartum depressive symptoms and support the development of personalized approaches to maternal mental wellness.

• Study Type: Observational
• Enrollment (Estimated): 30

Contacts and Locations

• Study Contact: Name: Jingping Wang, MD PhD; Phone Number: 6179369136; Email: jwang23@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Meikun Wang
      • Contact: Meikun Wang, MD; Phone Number: 6179369136; Email: wangmkjdyy@jlu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Women aged 18 years or older, with gestational age of at least 36 weeks, planning either vaginal or cesarean delivery. Individuals with serious digestive disorders, severe mental health conditions, or recent use of medications such as antibiotics or antidepressants that may affect gut bacteria are excluded.

Description

Inclusion Criteria:

• Age 18 years or older
• Gestational age at least 36 weeks, planned cesarean delivery
• Ability to understand study procedures and provide informed consent
• Voluntary agreement to participate in the study

Exclusion Criteria:

• Gastrointestinal disorders or recent antibiotic use that significantly alters gut microbiome
• Diagnosis of severe mental illness such as schizophrenia, schizoaffective disorder, bipolar disorder, or major depressive disorder with psychotic features
• Medication use during pregnancy known to influence gut microbiota, including antidepressants, antibiotics, or fish oil
• Refusal to provide rectal swab samples or inability to complete follow-up assessments

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
High-Edinburgh Postnatal Depression Scale cohort; Pregnant participants with antepartum Edinburgh Postnatal Depression Scale (EPDS; range 0-30; higher scores indicate more depressive symptoms) ≥13. Peripheral venous blood (serum) and rectal swab collected ≤3 days pre-delivery and ≤2 days postpartum; optional 6-week follow-up. Observational only-no interventions assigned.
Low-Edinburgh Postnatal Depression Scale cohort; Pregnant individuals with antepartum Edinburgh Postnatal Depression Scale (EPDS; range 0-30; higher scores indicate more depressive symptoms) <13; same specimen collection and follow-up schedule as the high-EPDS cohort; no interventions assigned.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
gut microbiota composition	Compare gut microbiota composition between participants with postpartum depression (defined as Edinburgh Postnatal Depression Scale (EPDS; range 0-30; higher scores indicate more depressive symptoms) ≥13) and without postpartum depression (EPDS <13).	within 3 days before delivery； within 2 days after delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association between inflammatory cytokines and postpartum depressive symptom severity	Association between serum inflammatory cytokines (e.g., Interleukin-6, Tumor Necrosis Factor-alpha) and depressive symptom severity measured by the Edinburgh Postnatal Depression Scale (EPDS; range 0-30; higher scores indicate more depressive symptoms).	Within 3 days before delivery; within 2 days after delivery
Edinburgh Postnatal Depression Scale (EPDS; range 0-30; higher scores indicate more depressive symptoms)	Edinburgh Postnatal Depression Scale (EPDS; range 0-30; higher scores indicate more depressive symptoms) will be administered within 3 days before delivery ; within 2 days after delivery; 6 weeks postpartum;	within 3days before delivery ; within 2 days after delivery; 6 weeks postpartum;
Changes in gut microbiota diversity (alpha and beta)	Alpha diversity (e.g., Shannon, Simpson, observed ASVs) and beta diversity (e.g., Bray-Curtis, UniFrac) will be calculated from rectal swab profiles. Change over time will be compared within participants.	within 3days before delivery ; within 2 days after delivery
Correlation between relative abundance of selected microbial taxa and maternal depressive symptom severity measured by the Edinburgh Postnatal Depression Scale (EPDS)	Association between the relative abundance of prespecified taxa (e.g., Lactobacillus, Clostridium) from rectal swabs and Edinburgh Postnatal Depression Scale (EPDS; 0-30, higher scores indicate more depressive symptoms) at each timepoint and longitudinally within participants.	within 3days before delivery ; within 2 days after delivery

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: National Institute on Aging (NIA)

Publications and helpful links

General Publications

• Sun Y, Fan C, Lei D. Association between gut microbiota and postpartum depression: A bidirectional Mendelian randomization study. J Affect Disord. 2024 Oct 1;362:615-622. doi: 10.1016/j.jad.2024.07.057. Epub 2024 Jul 17.
• Bevilacqua G. [Prevention of perinatal infection caused by group B beta-hemolytic streptococcus]. Acta Biomed Ateneo Parmense. 1999;70(5-6):87-94. Italian.
• Binka FN, Mensah OA, Mills A. The cost-effectiveness of permethrin impregnated bednets in preventing child mortality in Kassena-Nankana district of Northern Ghana. Health Policy. 1997 Sep;41(3):229-39. doi: 10.1016/s0168-8510(97)00035-3.

Study record dates

Study Major Dates

• Study Start (Actual): November 17, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): May 1, 2026

Study Registration Dates

• First Submitted: November 10, 2025
• First Submitted That Met QC Criteria: November 11, 2025
• First Posted (Estimated): November 13, 2025

Study Record Updates

• Last Update Posted (Actual): January 15, 2026
• Last Update Submitted That Met QC Criteria: January 14, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: depression; postpartum
• Additional Relevant MeSH Terms: Behavioral Symptoms; Behavior; Depression
• Other Study ID Numbers: 2025P002566; 5R21AG081763 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data will not be shared. The dataset contains sensitive clinical information from pregnant and postpartum patients at a single institution.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No