Abstract
Background
Depression and anxiety are common during pregnancy and postpartum, affecting both mothers’ and offspring health. Emerging research suggests gut microbiota may influence these conditions, providing a potential non-pharmacological approach for primary prevention, particularly in women without a prior mental health diagnosis.
Aim
To assess the effect of prebiotics, probiotics, and synbiotics as dietary interventions targeting gut microbiota for preventing mental health disorders during pregnancy and postpartum in women without diagnosed mental health disorders.
Methods
The protocol was prospectively registered in PROSPERO (CRD42024576678). A comprehensive search of MEDLINE, EMBASE, CINAHL, The Cochrane Library (CENTRAL), Scopus, and Web of Science from inception to March 2025, without language restriction. Randomized controlled trials (RCTs) involving pregnant or early postpartum women without a diagnosed mental health disorder, evaluating prebiotics, probiotics, or synbiotics and reporting maternal mental health outcomes, were included. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool.
Results
Of the 1,401 records identified, four RCTs (n = 1,342 women) met the inclusion criteria. All RCTs evaluated probiotics interventions, none assessed prebiotics or synbiotics. Of four, two RCTs using Lactobacillus rhamnosus HN001, Limosilactobacillus reuteri PBS072 and Bifidobacterium breve reported small but significant reductions in depressive symptoms [Edinburgh Postnatal Depression Scale, MD = −1.2; 95% CI (−2.3, −0.1)] and anxiety symptoms [State–Trait Anxiety Inventory-6: MD = −1.0; 95% CI (−1.9, −0.2); p < 0.05)] during pregnancy. One RCT showed significantly lower depressive scores in the intervention group at day 45 (mean 9.0 ± 4.8 vs. 12.1 ± 5.9; p < 0.001) and day 90 (7.0 ± 3.3 vs. 10.8 ± 6.2; p < 0.001) of postpartum compared to placebo. No pooled analyses were conducted due to heterogeneity. Risk of bias was moderate in three RCTs and high in one, primarily due to selective outcome reporting.
Conclusion
Evidence on the effect of probiotics for preventing maternal mental health disorders during pregnancy and postpartum is limited. There were no data on prebiotics or synbiotics. Strain specific probiotic effectiveness studies, as well as studies on prebiotics and synbiotics are required in the future.
Systematic review registration
PROSPERO, identifier (CRD42024576678).
Keywords: anxiety disorder, depressive disorder, microbiota, postpartum, pregnancy
1. Introduction
Maternal mental health disorders affect about one in five women during pregnancy and the first postpartum year, with depression and anxiety being most common conditions (1). These disorders are linked to adverse outcomes for both maternal well-being and infant development (2). Although pharmacotherapy is a mainstay treatment, concerns about maternal and fetal safety have increased interest in alternative approaches (3). Non-pharmacological interventions, such as cognitive-behavioural therapy and exercise, have shown potential benefits (4). Recent studies suggest a relationship between maternal mental health disorders and the gut microbiota through the gut–brain axis (5). The gut microbiota influences the central nervous system via autonomic, hormonal and immune pathways and has been associated with psychological disorders (6–8). Pregnancy induces physiological changes in gut microbiota composition (9, 10), while environmental disturbances may negatively affect maternal biology and mental health (11, 12). Maternal microbiota perturbations may influence offspring development through microbiota-derived fetal programming and early-life microbial transmission from mother to infant (13, 14).
Importantly, gut microbiota composition is modifiable through lifestyle factors, particularly diet. Dietary patterns, specific nutrients, and microbiota-targeted interventions such as probiotics, prebiotics and synbiotics have shown mental health benefits (15–18). Despite growing interest in microbiota-targeted interventions, evidence on their role in primary prevention of maternal mental health problems remains limited (19–21). In this context, prevention refers to interventions applied in women without a prior clinical diagnosis, aimed at reducing symptom severity or the risk of progression to clinically relevant disorders, rather than preventing formally diagnosed conditions. Previous systematic reviews have reported heterogeneous findings and methodological limitations, and none incorporated prebiotic or synbiotic interventions (19, 20). Moreover, their methodological quality assessed using AMSTAR-2 was low (Supplementary material 1). These limitations justify the need for an updated systematic review to evaluate current evidence and identify research gaps.
This systematic review aims to evaluate the available evidence and identify research gaps regarding the effect of prebiotics, probiotics, and synbiotics as dietary interventions targeting gut microbiota to prevent mental health disorders during pregnancy and postpartum in women without diagnosed mental health disorders.
2. Methods
This systematic review was carried out in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (22). A protocol for this review was registered in the International prospective register of systematic reviews (PROSPERO ID: CRD42024576678).
2.1. Search strategy and selection criteria
A comprehensive bibliographic search was conducted (Supplementary material 2) across the electronic databases, MEDLINE, EMBASE, CINAHL, The Cochrane Library (CENTRAL), Scopus, Proquest Dissertations and Theses, and Web of Science Core Collection, from inception to March 2025. The search strategy, developed by a health sciences librarian (CHC), focused exclusively on randomized controlled trials (RCTs), excluding animal studies. No restrictions on language or publication date were applied.
Only randomized controlled trials (RCTs) evaluating prebiotic, probiotic, and/or synbiotic supplementation (PPS) conducted in pregnant women without a diagnosis of mental health disorder were included. The absence of a mental health disorder was defined according to the inclusion criteria of each individual trial and was generally based on self-report and/or the absence of a prior clinical diagnosis, rather than on structured psychiatric interviews. The presence of subthreshold depressive or anxiety symptoms was not an exclusion criterion in most studies, which is consistent with a primary prevention framework but limits conclusions regarding clinically diagnosed disorders.
The intervention of interest was PPS, alone or in combination compared to treatment as usual, standard advice or a placebo control group. The primary outcomes reviewed were measures of maternal mental health (well-being, anxiety, depression, stress, mood, nervous, obsession, etc. For more terms used, see Supplementary material 2) during pregnancy and the postpartum period. As secondary outcomes, health problems and changes in the gut microbiota of the mother or offspring were reviewed. Review articles, editorials, letters, case series, case reports, quasi-experimental studies and observational studies were excluded from the review.
After duplicates were removed, the selection process was conducted in two phases: first, titles and abstracts were screened for relevance, followed by a review of the full text to ensure that the inclusion criteria were met. Two independent reviewers (LMMR and SMP) carried out the screening process with the help of the Rayyan application (23). Disagreements between reviewers were resolved by discussion or, when necessary, by consulting a third reviewer to reach consensus (NCI). Reasons for exclusion were further documented (Supplementary material 3).
2.2. Data extraction
Data extraction was performed by two independent reviewers (LMMR and SMP) using a standardized form. The following information was collected for each included study: study characteristics (author, year of publication, setting, sample size), participant characteristics (age, gestational stage), intervention details (type, dose, duration of probiotics, prebiotics or synbiotics intervention in experimental and control group), primary outcome (type of mental disorder and measurement tool), secondary outcomes (type of health disorder/changes in maternal or newborn gut microbiota and measurement tool). Reported side effects or adverse reactions were also recorded. All reported mean differences (MDs) correspond to individual study estimates, as reported in the original publications. Results were synthesized using a structured narrative approach, with findings presented at the individual study level.
Discrepancies between reviewers (LMMR and SMP) were resolved by discussion. When consensus was not reached, a third reviewer (NCI) was consulted to ensure accurate and comprehensive data extraction.
The quality of the included studies was assessed using the Risk of Bias 2 (ROB2) tool (24). This tool assesses the risk of bias in RCTs in five domains: Randomization process, Deviations from intended interventions, Missing outcome data, Outcome measurement, and Selection of reported outcome. Each domain was classified as “low risk,” “some concern,” or “high risk” based on the criteria described in the ROB2 tool. The overall risk of bias for each study was determined by considering the ratings across all domains. This quality assessment was performed by two independent reviewers (LMMR and SMP), and disagreements between reviewers were resolved by discussion or, when necessary, by consulting a third reviewer to reach consensus (NCI).
2.3. Evidence synthesis
We tabulated the findings and constructed graphs as appropriate. Due to small number of studies, statistical synthesis was not performed.
3. Results
A total of 1,401 records were identified through database searches. After screening titles and abstracts, 11 records were assessed for eligibility. Of these, 6 were excluded based on predefined inclusion criteria, remaining 5 full-text articles for further evaluation. Ultimately, after removal of one study because it included women diagnosed with a mental health disorder, 4 studies met all inclusion criteria and were included in this systematic review (Figure 1).
Figure 1.
PRISMA 2020 flow diagram for the systematic reviews including searches of databases, registers, and other sources.
4. Characteristics and quality of included studies
The included studies were carried out in New Zealand (25), Finland (26), Iran (27), and Italy (28). The publication dates ranged from 2016 to 2023. The total number of participants varied from 60 (27) to 439 (26), with a cumulative total of 1,342 women included in this review. The gestational age at the start of the trials did not exceed 28 weeks, and the participants’ ages ranged from 16 (25) to 50 years (28) (Table 1). The four RCTs included probiotics in the interventions. The probiotic strains used were Lactobacillus rhamnosus HN001 (25, 26), Bifidobacterium animalis ssp. lactis 420 (26), Limosilactobacillus reuteri PBS072 (28), Bifidobacterium breve BB077 (28), Lactobacillus acidophilus La-5 and Bifidobacterium lactic Bb-12 (27). The probiotic daily dose varied from 4 × 109 CFU (28) to 4.8 × 1010 CFU (27), administered in capsules with the exception of one study, which used yogurt as probiotic vehicle (27). Intervention duration ranged from 4 weeks (27) to 48 weeks (25), and occurred during pregnancy only (27), both pregnancy and postpartum (25, 26) or only postpartum (28). From the four studies, three investigated mental health as primary outcome (25, 26, 28). The mean intervention follow-up rated from 12 to 24 months (Table 2).
Table 1.
Characteristics of the studies.
| Author, year | Country | RCT design | Population | ||
|---|---|---|---|---|---|
| Sample Size (intervention/Control) | Inclusion criteria | Exclusion criteria | |||
| Hulkkonen et al. (26) | Finland | Double-blind, 2×2 factorial parallel groups | N = 439 (split into 4 groups) | 1) Age: Not specified 2) Type of pregnancy: Singleton 3) GW: ≤ 18 weeks of gestation 4) BMI: ≥ 25 Kg/m2 5)Absence of chronic diseases (except for asthma and allergies) |
Multifetal pregnancy, the presence of inflammatory, metabolic or gastrointestinal diseases diagnosis or history of coagulopathy, and use of anticoagulants. The women who became pregnant again before 12 months postpartum were excluded from the postpartum analyses |
| Mirghafourvand et al. (27) | Iran | Triple-blind, two parallel groups | N = 60 (30/30) | 1) Age: >18 years 2) GW: between 24–28 weeks of gestation 4) Women suffered from constipation 5) Being literate and willing to participate in the study |
Receiving any treatment in less than a week before the study, having mental retardation or metabolic disease (hypothyroidism), Hirschsprung disease, spinal anomalies, anorectal pathology, inflammatory of bowel disease, previous gastrointestinal surgery and use of fermented dairy products containing probiotics 2 weeks prior to the study |
| Slykerman et al. (25) | New Zealand | Double-blind, two center | N = 423 (212/211) | 1) Age: >16 years 2) GW: between 24–28 weeks of gestation 4) English-speaking 5) Planning to breastfeed 6) They or the unborn child’s biological father had a history of asthma, hay fever or eczema requiring medication |
Women were excluded from the study if aged < 16 years, planning to move outside the study centers during study duration, planning on taking probiotics, or if they had serious medical or health problems related to the pregnancy |
| Vicariotto et al. (28) | Italy | Double-blind, multicenter, two parallel groups | N = 190 (95/95) | 1) Age 18–50 years old 2) Women in the first trimester postpartum 3) Good general health condition 4) Willingness to: breastfeed, use probiotics and multivitamin food supplements consigned at the last visit before delivery, fill up questionnaires, use only the products to be tested during the entire study period, not to use similar products that could interfere with the product to be tested, not to vary the normal daily routine (i.e., lifestyle, physical activity, etc.) 5) Subjects aware of this study’s procedures and having signed an informed consent form |
1) Subjects who do not meet the inclusion criteria 2) Subjects considered as not adequate to participate in this study by the investigator 3. Subjects with known or suspected sensitization to one or more test formulation ingredients 4) Adult protected by law (under control or hospitalized in public or private institutions for reasons other than research or incarcerated) 5) Subjects not able to communicate or cooperate with the investigator due to problems related to language, mental retardation, or impaired brain function 6) Subjects suffering from other psychiatric disorders such as schizophrenia, other psychotic disorders, bipolar disorder, or substance use disorder 7) Subjects with serious physical illnesses or mental disorders 8) Subjects with significant risk of infanticide according to the investigator’s assessment 9) Subjects taking herbal remedies or psychotropic drugs intended for depression and taken within the last 2 weeks prior to baseline or during this study 10) Subjects receiving counselling or psychological therapies at baseline or during this study |
Table 2.
Summary of main results.
| Author, year | Intervention | Control** | Mental health outcomes | ||||||
|---|---|---|---|---|---|---|---|---|---|
| Type | Bacterial strains | Dose | Duration | Type | Type | Test | Period | Results | |
| Hulkkonen et al. (26) | Fish oil and Probiotics* | Lactobacillus rhamnosus HN001 and Bifidobacterium animalis ssp. lactis 420 | 1 capsule/day containing 10^10 CFU per strain | Enrolment (≤18 GW) to 6 months postpartum | Placebo for the probiotics: capsule containing microcrystalline cellulose Placebo for fish oil: capsule containing medium chain fatty acids |
Depressive and anxiety symptoms | EPDS (Ediburgh Posnatal Depression Scale) SCL-90 (Symptom Checklist-90) |
Early pregnancy and late pregnancy and at three, six and 12 months postpartum | No differences among intervention groups and placebo |
| Mirghafourvand et al. (27) | Probiotics | Bifidobacterium lactic (Bb-12) and Lactobacillus acidophilus (La-5) | 300 grams of yogurt containing 4.8 × 10^10 CFU (combined strains), 100 g x three times a day | Four weeks | Conventional yogurt, identical appearance | Quality of life | SF-36 (Quality of life questionnaire) | At baseline and at the end of week 6 | No differences among intervention group and placebo |
| Slykerman et al. (25) | Probiotic | Lactobacillus rhamnosus HN001 | 1 capsule/day containing 6 × 10^9 CFU | Enrolment until birth and, from birth up till 6 months post-birth whilst breastfeeding | Capsules containing corn-derived maltodextrin, identical appearance | Depressive and anxiety symptoms | EPDS (Ediburgh Posnatal Depression Scale) STAI-6 (State Trait Anxiety Inventory-6) |
Mothers (baseline and after 6 months or 12 months after delivery) completed the surveys based on how they remember they felt when their child was 1–2 months old | Depression: The intervention group reported significantly lower scores (7.7 ± 5.4) than placebo (9.0 ± 6.0). Mean difference −1.2 (−2.3, −0.1), p = 0.037 Anxiety: The intervention group also reported lower scores (12.0 ± 4.0 vs. 13.0 ± 4.3). Mean difference: −1.0 (−1.9, −0.2), p = 0.014 |
| Vicariotto et al. (28) | Probiotics and plus multivitamin food supplement | Limosilactobacillus reuteri PBS072 and Bifidobacterium breve BB077 | 1 capsule/day containing 4 × 10^9 CFU/day (2 × 10^9 CFU for each strain) | 90 days | The same capsules without the probiotic strains (identical appearance) | Postpartum depression symptoms | EPDS (Ediburgh Posnatal Depression Scale) | 45 days after the beginning of the treatment and final visit (i.e., 90 days after the beginning of the treatment) | At day 45, the intervention group showed a significantly lower mean score (9.0 ± 4.8) compared to the control group (12.1 ± 5.9) (p < 0.001). On day 90, the intervention group showed a significantly lower mean score (7.0 ± 3.3) compared to the control group (10.8 ± 6.2) (p < 0.001). |
*In this study, the two interventions were combined in four groups with the control, resulting in the following organization: (1) Fish oil + placebo, (2) probiotics + placebo, (3) fish oil + probiotics and (4) placebo + placebo. ** In all studies, the duration and dose of placebos was identical to the intervention.
Of the included studies, one was classified as a high risk (Figure 2), the remaining 3 studies were classified as moderate. Among the ROB2 domains (Figure 3), the most frequent critical weakness identified was the risk of bias in the selection of the reported outcome.
Figure 2.
Risk of bias assessment of the included studies across individual domains and overall judgment.
Figure 3.
Summary of overall risk of bias across domains for the included studies.
4.1. Primary outcomes
Depressive (n = 3) and anxiety (n = 2) symptoms were the most frequently assessed outcomes, measured using tools such as the Edinburgh Postnatal Depression Scale (EPDS) (25, 26, 28), the State Trait Anxiety Inventory-6 (STAI-6) (25) and the Symptom Checklist-90 (SCL-90) (26). In addition, one study measured quality of life using the quality-of-life questionnaire (SF-36) (27), which assesses aspects such as emotional problems, emotional well-being and related domains (Table 2).
Regarding depressive or anxiety symptoms during pregnancy, one study (26) found not statistically significant differences between intervention Lactobacillus rhamnosus HN001 plus Bifidobacterium animalis ssp. lactis 420 and control groups, although minor variations were observed at 12 months of follow-up in EPDS test scores between the intervention groups containing fish oil and placebo versus probiotics and placebo (MD = −1.12, p = 0.039). In contrast, another study (25) reported significant reductions in depression mean differences (MD) scores in the intervention group (Lactobacillus rhamnosus HN001) compared to the control [MD = −1.2 95% CI (−2.3, −0.1)] and anxiety mean scores [MD = −1.0 95% CI (−1.9, −0.2)]. Regarding postpartum depression, one study (28) reported that at day 45, the intervention group (Limosilactobacillus reuteri PBS072 plus Bifidobacterium breve BB077) showed a significantly lower mean score (9.0 ± 4.8) compared to the control group (12.1 ± 5.9) (p < 0.001) and at day 90 (7.0 ± 3.3 vs. 10.8 ± 6.2, p < 0.001) (Table 2). Another study (27) showed not significant differences between intervention (Lactobacillus acidophilus La-5 plus Bifidobacterium animalis subsp. lactis Bb-12) and control groups regarding quality of life.
4.2. Secondary outcomes
From the 4 studies included in the review, only one (28) reported information about the secondary outcomes. Using the Breastfeeding Self-Efficacy Scale—Short Form (BSES-SF), they found that 45 and 90 days after the beginning of the intervention, breastfeeding quality and the baby’s crying/fussing significantly improved in the probiotic group. At 45 days postpartum, 81% of mothers in the intervention group reported improvement in crying/fussing events compared with 42% in the control group, while at 90 days postpartum the corresponding figures were 78 and 43%, respectively. In addition, the mean daily number of crying/fussing events was significantly lower in the probiotic group compared with the control group at both time points (p < 0.001).
5. Discussion
The evidence obtained in this study on the effect of prebiotics, probiotics, and synbiotics for preventing maternal mental health disorders is limited and heterogeneous. Only four RCTs met inclusion criteria, all focused on probiotics, highlighting a major research gap regarding prebiotics and synbiotics (19, 20). Importantly, by explicitly including prebiotics and synbiotics in the research question and search strategy, this review provides an updated assessment of the current evidence base and clearly demonstrates the absence of eligible RCTs for these interventions in perinatal mental health. While two trials reported improvements in depressive and anxiety symptoms (25, 28) others found no significant effects on mental health outcomes or quality of life (26, 27), in line with previous systematic reviews showing mixed results (19–21).
Importantly, the available evidence pertains to symptom-based outcomes rather than clinically diagnosed mental health disorders. Most studies allowed the presence of subthreshold symptoms and relied on self-reported measures rather than structured diagnostic interviews. Therefore, findings should be interpreted within a primary prevention framework focused on symptom reduction, rather than prevention of diagnosed mental health disorders.
Although secondary outcomes were reported in only one included trial, breastfeeding-related outcomes and infant crying/fussing are indirectly relevant to maternal mental health in the postpartum period. Postpartum depressive symptomatology has been consistently associated with less favorable infant-feeding outcomes, including breastfeeding difficulties and lower breastfeeding self-efficacy (29, 30). Moreover, evidence from systematic reviews and cohort studies indicates that excessive or inconsolable infant crying is associated with maternal depressive and anxiety symptoms, suggesting bidirectional and stress-mediated pathways (31–33). Nevertheless, because these secondary outcomes were reported in only one included trial, they should be interpreted cautiously and cannot be generalized.
Methodological heterogeneity likely explains these discrepancies, including wide variation in participant age (25, 28), intervention duration (27), probiotic strains and doses (34), and outcome measures. Some strains, such as Lactobacillus rhamnosus HN001 showed promising effects (25), but findings remain inconclusive due to limitations such as retrospective data collection and high dropout rates (26, 35). Other strains demonstrated benefits in specific populations or contexts (28, 36–40), suggesting context- and strain-specific effects.
Additional limitations include lack of standardized dosing (41), inadequate control of antibiotic use by participants in RCTs (25, 26, 28), reliance on self-reported adherence (42, 43), high microbiota variability (44, 45), heterogeneity in psychological instruments with varying validity (25, 26, 46–52) and absence of structured clinical interviews (53). Together, these issues underscore the need for well-designed, standardized RCTs to clarify the role of probiotics in maternal mental health.
5.1. Strengths and limitations
This systematic review followed PRISMA guidelines and was prospectively registered in PROSPERO, ensuring transparency and reproducibility. The search strategy was comprehensive, developed with a health sciences librarian, and applied across multiple databases without language or date restrictions. Study selection, data extraction, and risk of bias assessment (ROB2) were performed independently by two reviewers, with disagreements resolved by a third reviewer.
Limitations mainly reflect the scarcity and heterogeneity of the available evidence. Only four RCTs were identified, all evaluating probiotics, with no eligible trials assessing prebiotics or synbiotics. Differences in probiotic strains, doses, intervention duration, and outcome measures limited comparability across studies and precluded meta-analysis. Finally, the limited geographic representation may reduce generalizability to other populations and settings.
6. Conclusion
Current evidence on the effect of probiotics for preventing mental health disorders during pregnancy and postpartum is limited and heterogeneous, with no RCTs evaluating prebiotics or synbiotics. Although some studies report symptoms reductions, heterogeneity in strains, doses, intervention duration, and measurement tools limit conclusions. Well-designed and adequately powered RCTs are needed where maternal depressive and anxiety symptoms are primary outcomes, using standardized and strain-specific interventions, appropriate doses and durations, and harmonized assessment tools. Future trials should also explicitly evaluate prebiotics and synbiotics, as these remain major evidence gaps in perinatal mental health research.
Acknowledgments
We thank Camila Higueras-Callejón for her expert contribution to the design of the search strategy, the selection of databases, and the management of references, including the removal of duplicate records.
Funding Statement
The author(s) declared that financial support was received for this work and/or its publication. This study was funded by Project “PI23/01866”, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union.
Footnotes
Edited by: Andrew C. Shin, Texas Tech University, United States
Reviewed by: Francesca Uberti, University of Eastern Piedmont, Italy
Parvathy Unnikrishnan, Amrita Vishwa Vidyapeetham University, India
Author contributions
SM-P: Conceptualization, Formal analysis, Supervision, Writing – original draft, Writing – review & editing. LM-d: Formal analysis, Methodology, Writing – original draft, Writing – review & editing. NC-I: Funding acquisition, Methodology, Supervision, Writing – review & editing.
Conflict of interest
The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Generative AI statement
The author(s) declared that Generative AI was not used in the creation of this manuscript.
Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.
Publisher’s note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material
The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2026.1776398/full#supplementary-material
References
- 1.World Health Organization. Guide for integration of perinatal mental health in maternal and child health services. Geneva: World Health Organization; (2022). [Google Scholar]
- 2.Rogers AM, Youssef GJ, Teague S, Sunderland M, Le Bas G, Macdonald JA, et al. Association of maternal and paternal perinatal depression and anxiety with infant development: a longitudinal study. J Affect Disord. (2023) 338:278–88. doi: 10.1016/j.jad.2023.06.020, [DOI] [PubMed] [Google Scholar]
- 3.Costa B, Vale N. Advances in psychotropic treatment for pregnant women: efficacy, adverse outcomes, and therapeutic monitoring. J Clin Med. (2024) 13:398. doi: 10.3390/jcm13154398, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Hidayati NO, Nuraeni A, Nurhidayah I, Rhamelani P, Nurjanah LS, Yani P, et al. Effect of non-Pharmachological therapies for pregnant women with mental disorder: a narrative review: effect of non-Pharmachological therapies for pregnant women with mental disorder: a narrative review. J Surya Med. (2024) 10:376–83. doi: 10.33084/jsm.v10i1.7239 [DOI] [Google Scholar]
- 5.Song J, Zhou B, Kan J, Liu G, Zhang S, Si L, et al. Gut microbiota: linking nutrition and perinatal depression. Front Cell Infect Microbiol. (2022) 12:932309. doi: 10.3389/fcimb.2022.932309, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EF, Wang J, Tito RY, et al. The neuroactive potential of the human gut microbiota in quality of life and depression. Nat Microbiol. (2019) 4:623–32. doi: 10.1038/s41564-018-0337-x, [DOI] [PubMed] [Google Scholar]
- 7.Sanada K, Nakajima S, Kurokawa S, Barceló-Soler A, Ikuse D, Hirata A, et al. Gut microbiota and major depressive disorder: a systematic review and meta-analysis. J Affect Disord. (2020) 266:1–13. doi: 10.1016/j.jad.2020.01.102, [DOI] [PubMed] [Google Scholar]
- 8.Simpson CA, Diaz-Arteche C, Eliby D, Schwartz OS, Simmons JG, Cowan CS. The gut microbiota in anxiety and depression–a systematic review. Clin Psychol Rev. (2021) 83:101943. doi: 10.1016/j.cpr.2020.101943 [DOI] [PubMed] [Google Scholar]
- 9.Koren O, Goodrich JK, Cullender TC, Spor A, Laitinen K, Bäckhed HK, et al. Host remodeling of the gut microbiome and metabolic changes during pregnancy. Cell. (2012) 150:470–80. doi: 10.1016/j.cell.2012.07.008, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Mesa MD, Loureiro B, Iglesia I, Fernandez Gonzalez S, Llurba Olive E, Garcia Algar O, et al. The evolving microbiome from pregnancy to early infancy: a comprehensive review. Nutrients. (2020) 12:133. doi: 10.3390/nu12010133, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Amato KR, Pradhan P, Mallott EK, Shirola W, Lu A. Host–gut microbiota interactions during pregnancy. Evol Med Public Health. (2024) 12:7–23. doi: 10.1093/emph/eoae001, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Armbruster M, Forsythe P. The perinatal microbiota-gut-brain Axis: implications for postpartum depression. Neuroimmunomodulation. (2025) 32:67–82. doi: 10.1159/000543691, [DOI] [PubMed] [Google Scholar]
- 13.Vuong HE, Pronovost GN, Williams DW, Coley EJ, Siegler EL, Qiu A, et al. The maternal microbiome modulates fetal neurodevelopment in mice. Nature. (2020) 586:281–6. doi: 10.1038/s41586-020-2745-3, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Hassib L, de Oliveira CL, Rouvier GA, Kanashiro A, Guimarães FS, Ferreira FR. Maternal microbiome disturbance induces deficits in the offspring’s behaviors: a systematic review and meta-analysis. Gut Microbes. (2023) 15:2226282. doi: 10.1080/19490976.2023.2226282, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.Swanson KS, Gibson GR, Hutkins R, Reimer RA, Reid G, Verbeke K, et al. The international scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of synbiotics. Nat Rev Gastroenterol Hepatol. (2020) 17:687–701. doi: 10.1038/s41575-020-0344-2, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Varesi A, Campagnoli LIM, Chirumbolo S, Candiano B, Carrara A, Ricevuti G, et al. The brain-gut-microbiota interplay in depression: a key to design innovative therapeutic approaches. Pharmacol Res. (2023) 192:106799. doi: 10.1016/j.phrs.2023.106799, [DOI] [PubMed] [Google Scholar]
- 17.Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. Activity of cecropin P1 and FA-LL-37 against urogenital microflora. Nat Rev Gastroenterol Hepatol. (2014) 11:506–514. doi: 10.1038/nrgastro.2014.66 [DOI] [PubMed] [Google Scholar]
- 18.Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. Expert consensus document: the international scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat Rev Gastroenterol Hepatol. (2017) 14:491–502. doi: 10.1038/nrgastro.2017.75 [DOI] [PubMed] [Google Scholar]
- 19.Trifkovic KC, Micetic-Turk D, Kmetec S, Strauss M, Dahlen HG, Foster JP, et al. Efficacy of direct or indirect use of probiotics for the improvement of maternal depression during pregnancy and in the postnatal period: a systematic review and meta-analysis. Healthcare. (2022) 2022:970. doi: 10.3390/healthcare10060970 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20.Halemani K, Shetty AP, Thimmappa L, Issac A, Dhiraaj S, Radha K, et al. Impact of probiotic on anxiety and depression symptoms in pregnant and lactating women and microbiota of infants: a systematic review and meta-analysis. J Glob Health. (2023) 13:04038. doi: 10.7189/jogh.13.04038, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21.Desai V, Kozyrskyj AL, Lau S, Sanni O, Dennett L, Walter J, et al. Effectiveness of probiotic, prebiotic, and synbiotic supplementation to improve perinatal mental health in mothers: a systematic review and meta-analysis. Front Psych. (2021) 12:622181. doi: 10.3389/fpsyt.2021.622181, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22.Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. (2021) 372:n71. doi: 10.1136/bmj.n71, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan—a web and mobile app for systematic reviews. Syst Rev. (2016) 5:210. doi: 10.1186/s13643-016-0384-4, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Sterne JA, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. (2019) 366:1–15. doi: 10.1136/bmj.l4898 [DOI] [PubMed] [Google Scholar]
- 25.Slykerman RF, Hood F, Wickens K, Thompson JMD, Barthow C, Murphy R, et al. Effect of Lactobacillus rhamnosus HN001 in pregnancy on postpartum symptoms of depression and anxiety: a randomised double-blind placebo-controlled trial. EBioMedicine. (2017) 24:159–65. doi: 10.1016/j.ebiom.2017.09.013, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Hulkkonen P, Kataja E-L, Vahlberg T, Koivuniemi E, Houttu N, Pellonperä O, et al. The efficacy of probiotics and/or n-3 long-chain polyunsaturated fatty acids intervention on maternal prenatal and postnatal depressive and anxiety symptoms among overweight and obese women. J Affect Disord. (2021) 289:21–30. doi: 10.1016/j.jad.2021.04.006, [DOI] [PubMed] [Google Scholar]
- 27.Mirghafourvand M, Rad AH, Charandabi SMA, Fardiazar Z, Shokri K. The effect of probiotic yogurt on constipation in pregnant women: a randomized controlled clinical trial. Iran Red Crescent Med J. (2016) 18:e39870. doi: 10.5812/ircmj.39870, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Vicariotto F, Malfa P, Torricelli M, Lungaro L, Caio G, De Leo V. Beneficial effects of limosilactobacillus reuteri PBS072 and bifidobacterium breve BB077 on mood imbalance, self-confidence, and breastfeeding in women during the first trimester postpartum. Nutrients. (2023) 15:3513. doi: 10.3390/nu15163513, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Dennis C-L, McQueen K. The relationship between infant-feeding outcomes and postpartum depression: a qualitative systematic review. Pediatrics. (2009) 123:e736–51. doi: 10.1542/peds.2008-1629, [DOI] [PubMed] [Google Scholar]
- 30.Ahmadinezhad GS, Karimi FZ, Abdollahi M, NaviPour E. Association between postpartum depression and breastfeeding self-efficacy in mothers: a systematic review and meta-analysis. BMC Pregnancy Childbirth. (2024) 24:273. doi: 10.1186/s12884-024-06465-4, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 31.Radesky JS, Zuckerman B, Silverstein M, Rivara FP, Barr M, Taylor JA, et al. Inconsolable infant crying and maternal postpartum depressive symptoms. Pediatrics. (2013) 131:e1857–64. doi: 10.1542/peds.2012-3316, [DOI] [PubMed] [Google Scholar]
- 32.Vik T, Grote V, Escribano J, Socha J, Verduci E, Fritsch M, et al. Infantile colic, prolonged crying and maternal postnatal depression. Acta Paediatr. (2009) 98:1344–8. doi: 10.1111/j.1651-2227.2009.01317.x [DOI] [PubMed] [Google Scholar]
- 33.Petzoldt J. Systematic review on maternal depression versus anxiety in relation to excessive infant crying: it is all about the timing. Arch Womens Ment Health. (2018) 21:15–30. doi: 10.1007/s00737-017-0771-4 [DOI] [PubMed] [Google Scholar]
- 34.Sarkar A, Lehto SM, Harty S, Dinan TG, Cryan JF, Burnet PWJ. Psychobiotics and the manipulation of bacteria-gut-brain signals. Trends Neurosci. (2016) 39:763–81. doi: 10.1016/j.tins.2016.09.002, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Dawe JP, McCowan LME, Wilson J, Okesene-Gafa KAM, Serlachius AS. Probiotics and maternal mental health: a randomised controlled trial among pregnant women with obesity. Sci Rep. (2020) 10:1291. doi: 10.1038/s41598-020-58129-w, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Valle MCPR, Vieira IA, Fino LC, Gallina DA, Esteves AM, da Cunha DT, et al. Immune status, well-being and gut microbiota in military supplemented with synbiotic ice cream and submitted to field training: a randomised clinical trial. Br J Nutr. (2021) 126:1794–808. doi: 10.1017/S0007114521000568, [DOI] [PubMed] [Google Scholar]
- 37.Sarkawi M, Raja Ali RA, Abdul Wahab N, Abdul Rathi ND, Mokhtar NM. A randomized, double-blinded, placebo-controlled clinical trial on Lactobacillus-containing cultured milk drink as adjuvant therapy for depression in irritable bowel syndrome. Sci Rep. (2024) 14:9478. doi: 10.1038/s41598-024-60029-2, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 38.Askarpour M, Hejazi N, Jahromi BN, Eskandari MH, Famouri M, Bedeltavana A. Effects of a novel fortified dairy product on the psychological status and sleep quality of patients with polycystic ovary syndrome: a double-blind randomized controlled trial. Prev Nutr Food Sci. (2025) 30:37–46. doi: 10.3746/pnf.2025.30.1.37, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Nobile V, Giardina S, Puoci F. The effect of a probiotic complex on the gut-brain Axis: a translational study. Neuropsychobiology. (2021) 81:116–26. doi: 10.1159/000518385, [DOI] [PubMed] [Google Scholar]
- 40.Freitas SM, Franco B, Saragiotto G, Morais MA, Simabuco FM, Cunha DT, et al. Effect of a probiotic fermented milk supplementation on behavior and sleep. Nutr Neurosci. (2024) 27:607–19. doi: 10.1080/1028415X.2023.2240990, [DOI] [PubMed] [Google Scholar]
- 41.Whorwell PJ, Altringer L, Morel J, Bond Y, Charbonneau D, O’Mahony L, et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol. (2006) 101:1581–90. doi: 10.1111/j.1572-0241.2006.00734.x [DOI] [PubMed] [Google Scholar]
- 42.Osterberg L, Blaschke T. Adherence to medication. N Engl J Med. (2005) 353:487–97. doi: 10.1056/NEJMra050100, [DOI] [PubMed] [Google Scholar]
- 43.Lam WY, Fresco P. Medication adherence measures: an overview. Biomed Res Int. (2015) 2015:217047. doi: 10.1155/2015/217047, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 44.Vandeputte D, De Commer L, Tito RY, Kathagen G, Sabino J, Vermeire S, et al. Temporal variability in quantitative human gut microbiome profiles and implications for clinical research. Nat Commun. (2021) 12:6740. doi: 10.1038/s41467-021-27098-7, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 45.Procházková N, Laursen MF, La Barbera G, Tsekitsidi E, Jørgensen MS, Rasmussen MA, et al. Gut environmental factors explain variations in the gut microbiome composition and metabolism within and between healthy adults. bioRxiv. (2024) 2024:574598. doi: 10.1038/s41564-024-01856-x [DOI] [Google Scholar]
- 46.Robinson PS, Balasundaram AP, Vøllestad NK, Robinson HS. The association between pregnancy, pelvic girdle pain and health-related quality of life – a comparison of two instruments. J Patient Rep Outcomes. (2018) 2:45. doi: 10.1186/s41687-018-0069-y, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 47.Martín-Vázquez C, Urchaga-Litago JD, García-Fernández R, Calvo-Ayuso N, Rosón-Matilla L, Liébana-Presa C. Psychometric analysis and validation of the SF-34 PREG: an adaptation of the SF-36 for assessing quality of life in pregnant women. Int J Gynecol Obstet. (2025) 168:743–52. doi: 10.1002/ijgo.15904, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 48.Alzboon G, Vural G. Factors influencing the quality of life of healthy pregnant women in North Jordan. Medicina. (2019) 55:278. doi: 10.3390/medicina55060278, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 49.Adhikari K, Patten SB, Williamson T, Patel AB, Premji S, Tough S, et al. Assessment of anxiety during pregnancy: are existing multiple anxiety scales suitable and comparable in measuring anxiety during pregnancy? J Psychosom Obstet Gynecol. (2021) 42:140–6. doi: 10.1080/0167482X.2020.1725462, [DOI] [PubMed] [Google Scholar]
- 50.Levis B, Negeri Z, Sun Y, Benedetti A, Thombs BD. Accuracy of the Edinburgh postnatal depression scale (EPDS) for screening to detect major depression among pregnant and postpartum women: systematic review and meta-analysis of individual participant data. BMJ. (2020) 371:m4022. doi: 10.1136/bmj.m4022, [DOI] [PMC free article] [PubMed] [Google Scholar]
- 51.Bergink V, Kooistra L, van den Lambregtse- Berg MP, Wijnen H, Bunevicius R, van Baar A, et al. Validation of the Edinburgh depression scale during pregnancy. J Psychosom Res. (2011) 70:385–9. doi: 10.1016/j.jpsychores.2010.07.008, [DOI] [PubMed] [Google Scholar]
- 52.Boyce P, Stubbs J, Todd A. The Edinburgh postnatal depression scale: validation for an Australian sample. Aust N Z J Psychiatry. (1993) 27:472–6. doi: 10.3109/00048679309075805, [DOI] [PubMed] [Google Scholar]
- 53.Zimmerman M, Walsh E, Friedman M, Boerescu DA, Attiullah N. Are self-report scales as effective as clinician rating scales in measuring treatment response in routine clinical practice? J Affect Disord. (2018) 225:449–52. doi: 10.1016/j.jad.2017.08.024, [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.