The gut microbiome consists of approximately 20-100 trillion microorganisms, encompassing at least a thousand distinct bacterial species (Sender et al., 2016). The microbiome – the combined genetic material of these microorganisms – may harbour over 100 times as many genes as the human genome (Gill et al., 2006). Variations in gut microbiome composition and diversity have been linked to a broad range of physical and mental health conditions (Lynch & Pederson, 2016), including major psychiatric disorders (Hashimoto, 2023).
A rapidly expanding body of research has explored the bidirectional relationship between the gut microbiota and the brain, commonly referred to as the gut–brain axis. Within this field of research, a limited number of studies have examined the association between gut microbiota and perinatal depression and anxiety symptoms (e.g., Xie et al., 2024; Zhou et al., 2020), finding associations between the abundance of certain bacteria and perinatal mental health.
Hieta et al. (2025) noted that the relationship between gut microbiota and perinatal depression and anxiety symptoms had not been explored for a pregnant population with overweight or obesity. Given that women with overweight or obesity are more likely to develop postnatal depression (Ertel et al., 2017), the authors thought it was important for them to explore this association.
Gut microbiota may hold clues to perinatal depression in women with higher body weight.
Methods
The study participants (n = 419) were a sub-sample of pregnant women (< 18 weeks gestation) with overweight and obesity (BMI ≥ 25) who were enrolled in a wider study on mother-child dietary intervention trial in Finland (ClinicalTrials.gov NCT01922791). The researchers excluded women who presented with the following:
- Chronic diseases that could influence metabolic or gastrointestinal health
- Pre-existing diabetes
- Multifetal pregnancies
- Antibiotics use within 8 weeks of supplying a faecal sample
- Did not supply a faecal sample
- Treated with metformin or insulin.
Symptoms of depression and anxiety were measured during early and late pregnancy as well as at 3, 6, 12 months postpartum. Depression symptoms were assessed using a questionnaire called the Edinburgh Postnatal Depression Scale (EPDS). Anxiety symptoms were assessed using a questionnaire called the 10-item Symptom Checklist 90 (SCL-90).
Each women’s gut microbiome was assessed using a faecal sample, and metagenomic sequencing was used to determine a range of relevant gut microbiome characteristics such as α-diversity (the variety of microbes within a single faecal sample), β-diversity (the variety of microbes between two or more faecal samples), and the number of specific bacteria.
The authors used latent growth mixture models (LGMM) to assess symptom trajectories over time. ANOVAs and t-tests (and their counterparts for non-normally distributed data) were used for group comparisons. Participants with missing data were included using maximum likelihood under the missing-at-random assumption. A range of other variables were used as co-variates in their statistical analyses, including pre-pregnancy BMI, intervention group, diet quality, and smoking status pre-pregnancy.
Results
There were 419 pregnant women included in this study, with an average age of 30.6 years. Most participants were overweight (60.6%) compared to obese (39.4%).
Depressive Symptoms
Differences in the relative abundance of specific gut bacteria across depressive symptom trajectories were found between women with ‘high and increasing’ symptoms vs those with ‘low and stable’ symptoms. Group differences were evident in early pregnancy for bacteria such as Clostridium sp AF27-2AA, GGB3571 SGB4778, Streptocuccus parasanguinis, and S. salivarius. Group differences were also observed in late pregnancy for bacteria Bacteroides clarus, B. faecis, and B. xylanisolvens. From early to late pregnancy, the abundance of B. clarus increased while Clostridium sp. AF27-2AA decreased. The authors speculate that the increased abundance of B. clarus could impact upon depression and anxiety symptoms via its pro-inflammatory effects.
Anxiety Symptoms
No group differences in anxiety symptom trajectories were found in early pregnancy. However, differences were observed in late pregnancy in the group classified as having ‘moderate and increasing’ symptoms vs those with ‘low and stable’ symptoms. A higher relative abundance was seen in Hydrogeniiclostidium mannosilyticum, B. xylanisolvens, Clostridiales bacterium Choco116, Flavonifractor plautii, GGB58158 SGB79798, Intestinimonas butyriciproducens, and Sellimonas intestinali. Changes from early to late pregnancy also showed increased abundance of Lachnospira SGB5076 and S. thermophilus in the ‘moderate and increasing’ group.
Clinically Significant Symptoms
The authors also looked at whether pregnant women with ‘clinically significant symptoms’ of depression or anxiety (i.e., those with a score of > 10 on the EPDS or SCL-90) had different relative amounts of specific gut bacteria compared to those without clinically significant symptoms. During pregnancy, clinically significant depression was associated with having higher abundance of bacteria GGB9634 SGB15093 and GGB9623 SGB15076. Women who had clinically significant depressive symptoms after giving birth were more likely to have higher abundances of bacteria GGB3277 SGB4327, GGB58158 SGB79798, and H. hathewayi. Drawing upon previous research in the field, the authors suggest that H. hathewayi could be associated with mental health outcomes via its pro-inflammatory signalling pathways.
Having clinically significant anxiety symptoms while pregnant was associated with having a higher relative abundance of bacteria Anaeromassilibacillus sp. An250, GGB3523 SGB4703, GGB9633 SGB15090, Parabacteroides goldsteinii, and Ruminococcaceae unclassified SGB15265. Postpartum anxiety was associated with higher relative abundance of bacteria B. clarus, Bifidobacterium pseudocatenulatum, Blautia massiliensis, Clostridium spiroforme, Eubacteriaceae bacterium, F. plautii, GGB9494 SGB14891, GGB9627 SGB15081, H. mannosilyticum, R. torques, and S. intestinalis. Additionally, the abundance of bacteria Candidatus Borkfalkia ceftriaxoniphila and Clostridia unclassified SGB4447 increased from early to late pregnancy among women with clinically significant anxiety symptoms during pregnancy.
No associations were found between α- or β-diversity of the gut microbiome and symptom trajectories or clinically significant depression or anxietysymptoms at any time point.
Distinct gut bacteria were linked to depression and anxiety symptom patterns in pregnant women with higher body weight, with specific microbial shifts observed across pregnancy. But overall microbiome diversity showed no association with mental health outcomes.
Conclusions
This study found that for pregnant women with overweight or obesity, elevated levels of certain bacteria were associated with their depression and anxiety symptom level and symptom trajectories during pregnancy and postpartum. Certain bacteria that were found to be elevated in those with more symptoms of depression and anxiety, such as B. clarus and H. hathewayi, are proposed to be pathogenic and are suggested by the authors to act on mental health via pro-inflammatory pathways. The authors concluded:
In the future, it would be important to investigate the maternal gut microbiota in relation to the children’s developmental outcomes.
The authors conclude “In the future, it would be important to investigate the maternal gut microbiota in relation to the children’s developmental outcomes”.
Strengths and limitations
By examining the association between gut microbiota and mental health outcomes in pregnant women with overweight or obesity, the authors have addressed a novel research question. The use of shotgun metagenomic sequencing (i.e., a method for analysing the genetic material of organisms) to analyse the gut microbiome enabled them to provide more information about specific bacteria at the species level compared to some other methods (e.g., 16S RNA sequencing), and measuring it at two timepoints during pregnancy also allowed them to examine change in the microbiome over time. The authors included some relevant covariates in their statistical models to control for possible confounders (pre-pregnancy BMI, intervention status (as they were part of a clinical trial), smoking status, diet quality). The authors said that participants were screened for illnesses that could impact upon gastrointestinal (GI) health, however, I would have liked to see a full list of which illnesses were screened for. Their clinical trial protocol (ClinicalTrials.gov NCT01922791) states that they excluded women with coeliac disease, but does not mention any other GI illness that could influence the gut microbiome such as inflammatory bowel disease or Crohn’s disease.
The authors selected an outcome measure for depression that has been validated for pregnant women (the EPDS), however, it is less clear whether the measure of anxiety (the anxiety sub-scale of the SCL-90) has been psychometrically validated for this population. A cutoff of >10 was used for both scales to denote women who were experiencing ‘clinically significant symptoms’ at each timepoint, but I would have liked the authors to provide a more robust justification for selecting this cutoff. They mention that the cutoff was determined based on two previous studies in the same geographical area (Mathiasen et al., 2023; Sirkia et al., 2024), however, these studies provide conflicting information, with Sirkia et al. (2024) using a cutoff of ≥7.5 for the SCL-90 and Mathiasen et al. (2023) using a cutoff of >12 for the EPDS. Following up depressive and anxiety symptoms at 3, 6, and 12 months postpartum was a strength of the study as it was an adequate time period for postpartum mental health issues to emerge, and allowed the authors to track the trajectory of symptoms over time.
Species-level microbiome analysis and longitudinal design strengthened the study, though gaps in illness screening, anxiety measure validation, and cutoff justification limit interpretability.
Implications for practice
The results of this study suggest that there are some differences in maternal gut microbiota, within a population with overweight and obesity, that are associated with perinatal anxiety and depressive symptoms. Although we cannot be certain that the relationship is causal, based only on this study, the results help us imagine a future where clinicians assess the gut microbiome of pregnant women as part of perinatal screening and address any issues that may be predictive of postpartum mental health issues. To get to this point, however, much more research will need to be conducted.
As this study was the first to explore associations between gut microbiota and symptoms of depression and anxiety in a population of pregnant women with overweight or obesity, it would be good to see if these results can be replicated across repeated studies, especially across diverse populations. If consistent differences are found in the abundance of specific bacterial species between high and low depression/anxiety groups, we would then need to see whether treatments that address these differences (e.g., probiotics) have an impact upon symptom progression.
Despite much ongoing research into associations between the gut microbiome and a range of health and disease outcomes (e.g., autoimmune diseases, neurodegenerative conditions such as Parkinson’s Disease, inflammatory bowel disease), there is currently only strong evidence to support the use of probiotics for a few conditions. One example is antibiotic-associated diarrhoea (AAD) in children, which occurs when antibiotics disturb the natural balance of gut bacteria and results in the proliferation of ‘bad’ bacteria within the gut microbiome. A Cochrane systematic review (Guo et al., 2019) suggested that taking specific probiotics could have a protective effect in preventing AAD and also shorten the duration of symptoms.
The authors of the present study suggest that the mechanism through which gut microbiome variations could be impacting upon symptoms of depression and anxiety is the immune system, specifically via bacterial metabolites that are pro-inflammatory. To improve confidence in immune-related mechanistic theories of the gut-brain-axis, future research on this topic could also include measures of inflammatory/immune-related markers and use analyses that strengthen causal interpretations such as Mendelian randomization.
Microbiome-based interventions like probiotics may hold promise for perinatal mental health, but clinical use will require stronger causal evidence, replication across diverse populations, and validation of immune-related mechanisms.
Statement of interests
No conflicts of interest to report.
Links
Primary paper
Hieta J, Benchraka C, Pärnänen K, et al (2025). Perinatal depressive and anxiety symptoms are associated with gut microbiota in pregnant women with overweight and obesity. Brain, behavior, & immunity – health, 47, 101042. https://doi.org/10.1016/j.bbih.2025.101042
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