Investigating the Microbiome in Relation to Mental Distress Across Two Points During Pregnancy: Data From U.S. and Swedish Cohorts

Mary Kimmel; Bangzhuo Tong; Alfons Edbom Devall; Richelle D Björvang; Ina Schuppe-Koistinen; Lars Engstrand; Emma Fransson; Alkistis Skalkidou; Luisa W Hugerth

doi:10.1016/j.bpsgos.2025.100453

Investigating the Microbiome in Relation to Mental Distress Across Two Points During Pregnancy: Data From U.S. and Swedish Cohorts

Biol Psychiatry Glob Open Sci. 2025 Jan 30;5(3):100453. doi: 10.1016/j.bpsgos.2025.100453. eCollection 2025 May.

Authors

Mary Kimmel^{1

2

3}, Bangzhuo Tong⁴, Alfons Edbom Devall^{4

5}, Richelle D Björvang¹, Ina Schuppe-Koistinen⁶, Lars Engstrand⁶, Emma Fransson^{1

6}, Alkistis Skalkidou¹, Luisa W Hugerth^{4

6}

Affiliations

¹ Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
² Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
³ Department of Psychiatry, Washington University, St. Louis, Missouri.
⁴ Department of Medical Biochemistry and Microbiology, Uppsala University, Science for Life Laboratory, Uppsala, Sweden.
⁵ Department of Molecular Biology, Umeå University, Umeå, Sweden.
⁶ Centre for Translational Microbiome Research, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

Abstract

Background: In this study, we aimed to characterize the gut microbiome and its potential functioning in 2 populations at 2 time points during pregnancy in relation to mental distress.

Methods: During the second and third trimester, individuals from the United States and Sweden completed the Edinburgh Postnatal Depression Scale and provided fecal samples for whole-genome metagenomics. A total of 832 and 161 samples were sequenced and analyzed from the Swedish cohort and the U.S. cohort, respectively. Multiple characterizations of the microbial community were analyzed in relation to distress measured using the Edinburgh Postnatal Depression Scale. Principal coordinate analysis and distance-based redundancy analysis assessed variation in functional gut-brain modules. For the U.S. cohort, the Trier Social Stress Test was administered 8 weeks postpartum while collecting salivary cortisol.

Results: Principal coordinate analysis identified 4 sample clusters based on the gut-brain modules distinguished by functions such as short-chain fatty acid synthesis and cortisol degradation. While with distance-based redundancy analysis, mental distress subtypes did not significantly contribute to variation in gut-brain modules (p = .085 for Sweden, p = .23 for the U.S.), a U.S. sample cluster distinguished by lower cortisol degradation from another cluster with higher gut microbial cortisol degradation abundance had significantly higher odds of being associated with depression (p = .024). The U.S. sample cluster with lower gut microbial cortisol degradation abundance also had significantly higher cortisol levels after a postpartum social stressor.

Conclusions: Further studies are warranted to investigate the potential for the gut microbiome to serve as biomarkers of gut-brain axis health during pregnancy across disparate populations.

Keywords: Cortisol; Mental distress; Microbiome; Pregnancy; Short-chain fatty acids.

Plain language summary

Pregnancy is a critical time for the mental health and development of parent and child. The results of the current study suggest that anxiety and depression during pregnancy may be distinguished by aspects of the gut microbiome, the bacteria that live within our intestinal tracts. This study suggests that we may be able to distinguish individuals by different functions of the community of bacteria. For example, a lower ability of a person’s microbiome to degrade the stress hormone cortisol may be associated with higher cortisol after a stressor and a higher likelihood of depression.