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. Author manuscript; available in PMC: 2024 Apr 15.
Published in final edited form as: Dev Psychobiol. 2024 Jan;66(1):e22441. doi: 10.1002/dev.22441

Selective serotonin reuptake inhibitors during pregnancy and lactation: A scoping review of effects on the maternal and infant gut microbiome

Katelyn Desorcy-Scherer 1, Hannah P Fricke 2, Laura L Hernandez 2
PMCID: PMC11017378  NIHMSID: NIHMS1983699  PMID: 38131241

Abstract

Perinatal mood disorders are a tremendous burden to childbearing families and treatment with selective serotonin reuptake inhibitor (SSRI) antidepressants is increasingly common. Exposure to SSRIs may affect serotonin signaling and ultimately, microbes that live in the gut. Health of the gut microbiome during pregnancy, lactation, and early infancy is critical, yet there is limited evidence to describe the relationship between SSRI exposure and gut microbiome status in this population. The purpose of this Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-compliant scoping review is to assess evidence and describe key concepts regarding whether SSRI exposure affects the maternal and infant gut microbiome. Sources were collected from PubMed, Web of Science, and Scopus databases, and an additional gray literature search was performed. Our search criteria returned only three sources, two rodent models and one human subjects research study. Results suggest that fluoxetine (SSRI) exposure may affect maternal gut microbiome dynamics during pregnancy and lactation. There were no available sources to describe the relationship between perinatal SSRI exposure and the infant gut microbiome. There is a significant gap in the literature regarding whether SSRI antidepressants affect the maternal and infant gut microbiome. Future studies are required to better understand how SSRI antidepressant exposure affects perinatal health.

Keywords: antidepressant, gut microbiome, lactation, perinatal, selective serotonin reuptake inhibitor, SSRI

1 |. INTRODUCTION

Perinatal mood disorders, occurring in a childbearing person during pregnancy and up to 12 months after delivery, affect up to 20% of the perinatal population and represent one of the most common complications of pregnancy and postpartum (The American College of Obstetrics & Gynecology, 2018; World Health Organization, 2023). Addressing perinatal mental health is a priority as mental health conditions represent a tremendous burden to pregnant and postpartum people and have recently been recognized as a leading cause of pregnancy-related deaths by the Joint Commission (The Joint Commission, 2023). The negative effects of perinatal mood disorders transcend maternal systems and a growing body of evidence suggests that maternal depression affects offspring brain development and function while increasing the risk of child and adolescent mental health problems (Fatori et al., 2020). First-line treatments for perinatal mood disorders include prescription of a common class of antidepressant medication, selective serotonin reuptake inhibitors (SSRIs). Approximately 13% of the perinatal population is treated with SSRI antidepressants and use has increased over the last two decades despite acknowledgment of potential risk to pregnant and lactating populations and a lack of satisfactory studies in pregnancy (Cooper et al., 2007; Hutchison et al., 2018; Petersen et al., 2021; Ramsteijn et al., 2020). The decision to start, continue, or cease SSRI therapy during pregnancy and lactation must be made with careful consideration of both the maternal and offspring health risks posed by untreated depression and exposure to a therapeutic that is supported by a limited body of evidence (Eakley & Lyndon, 2022). Patients report the decision to be distressing and suggest that provider and patient information sources and experience of the decision-making process differ significantly (Eakley & Lyndon, 2022). Gestation and early infancy are recognized as unique windows of plasticity by the developmental origins of health and disease theory (DOHaD), which suggests that exposures during this period may influence long-term health and susceptibility to disease (Gillman, 2005). Perinatal SSRI treatment is an exposure, and although SSRIs are designed to function in the central nervous system, they can have off-target effects in the periphery, including the gut, where greater than 90% of the body’s serotonin is produced (Fung et al., 2019). Gastrointestinal complaints are among the most commonly reported side effects of SSRI use, potentially due to off-target, systemic effects secondary to increased serotonin signaling (Wang et al., 2022). The gut is host to the gut microbiota, a community of microorganisms that has garnered increasing attention in recent years among rising acknowledgment of microbial influence on health and, in infants specifically, developmental programming (Underwood et al., 2020). Microorganisms in the gut may be affected by changes in serotonin availability, considering that some bacteria can use serotonin in cellular processes (Fung et al., 2019). The dynamic state of the gut microbiome during pregnancy and early infancy, combined with its developmental potential and ability to utilize gut-derived serotonin, makes the relationship between health of the maternal or infant gut microbiome and SSRI exposure a research priority.

The maternal and infant gut microbiome, although located in the gastrointestinal tract, are related to health and well-being of the maternal and infant dyad. During gestation, the maternal gut microbiome is thought to produce metabolites with the potential to affect the pregnancy and maturation of fetal tissues and systems (Jiang et al., 2023). Short-chain fatty acids produced by the gut microbiome are widely recognized for their influence on systemic physiology and have been shown to affect maternal weight gain, glucose metabolism, hormone homeostasis, and blood pressure (Edwards et al., 2017). A growing body of research also associates the maternal gut microbiome with infant outcomes. For example, researchers found that diversity of the maternal gut microbiome during the third trimester of pregnancy may be related to child internalizing behavior at 2 years of age (Dawson et al., 2021). Furthermore, the maternal gut microbiome may shape development of the infant microbiome. Microbes from the maternal gut may be vertically transferred to offspring, particularly in vaginally born infants (Bäckhed et al., 2015; Drell et al., 2017). The infant gut microbiome is critically involved in development of intestinal tissues, gut barrier integrity, training of the immune system, and metabolic processes (Underwood et al., 2020). A robust infant gut microbiome is considered a protective factor against intestinal morbidities such as necrotizing enterocolitis in vulnerable infant populations (Underwood et al., 2020). Composition of the infant gut microbiome has also been linked to long-term metabolic susceptibility and development of diseases such as obesity and type I diabetes (Bélteky et al.,2023; Cox et al., 2014).

In vitro studies suggest that changes in gut serotonin availability can directly affect colonization of bacteria in the gut microbiome that engage in bidirectional signaling with the host serotonergic system (Fung et al., 2019). While recent research has shown that SSRI medication can affect gut microbiome composition of nulliparous animals and adult humans (Cussotto et al., 2019; Fung et al., 2019; Jackson et al., 2018), there has been limited investigation in maternal and infant populations (Ramsteijn et al., 2020) despite the increasing use of SSRI antidepressants during the perinatal period (Petersen et al., 2021). Therefore, we performed a scoping review of existing literature to assess the state of available evidence and describe key concepts regarding whether SSRI exposure affects the gut microbiome of pregnant or lactating populations and their infants.

2 |. MATERIALS AND METHODS

2.1 |. Search strategy

This scoping review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist. A senior academic librarian from the University of Wisconsin library system was consulted prior to onset of the project, who guided project search procedures and assisted in development of the review protocol. Sources investigating the effects of perinatal SSRI exposure on the maternal or infant gut microbiome were included in the review through a search of PubMed, Web of Science, and Scopus databases. Additionally, a gray literature search using Google Scholar was conducted to identify any works such as preprints, theses, or dissertations. Full search strategies and a protocol for the scoping review are included in Supporting Information S1.

2.2 |. Study selection

Inclusion criteria required that sources investigate the influence of at least one SSRI on the maternal or infant gut microbiome as either a primary or nonprimary aim. Observations of maternal SSRI exposure and impacts on the maternal and infant gut microbiome were included, even if investigation into SSRI exposure was not an established purpose a priori and resulted from descriptive or inferential analyses. These criteria established an expansive scope and allowed the review team to utilize all sources of available information to effectively identify gaps in the literature. In maternal models, sources were included if the gut microbiome was assessed during pregnancy and/or lactation. In consideration of the infant gut microbiome, sources that investigated the influence of an SSRI on the gut microbiome during birth to 1 year of life in human populations or weaning in animal models (approximately 21 days in rodents) were included. All primary sources of evidence, including abstracts and conference proceedings, were considered. Review articles were excluded as a nonprimary source. Those written in languages other than English were excluded due to the inability for investigators to assess the content. Sources published from 1990 through December 16, 2022 were considered for review.

Screening, review, and management of sources were conducted using the Covidence tool. Study selection was performed independently by two reviewers (K.D.-S. and H.F.). Reviewers assessed sources for the initial title and abstract screen independently using the preestablished scoping review protocol and met face-to-face to resolve discrepancies. Sources identified for full text review were discussed by reviewers in detail. Full illustration of the search procedures is detailed in Figure 1.

FIGURE 1.

FIGURE 1

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Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) flow diagram of search strategy.

2.3 |. Data collection, synthesis, and analysis

Data were extracted independently by reviewers following a custom extraction template (Supporting Information S2) and uploaded into the Covidence tool. The template included general characteristics of the studies such as study design, aims, and funding sources. Additionally, it included descriptions of methods, participants, and outcomes tailored by reviewers to specifically address key concepts related to microbiome studies that were conducted in either animal or human models. Microbiome-specific outcomes were assessed, and they included any description of the gut microbiome using alpha diversity (Shannon, Chao1, etc.), beta diversity (principal coordinate analysis, nonmetric multidimensional scaling, etc.), or metrics of community composition (relative abundance, total abundance, etc.). Data resulting from other applied omics technologies such as metabolomics were not recorded as it represents a distinct functional (rather than observational) assessment. Data extracted using the template were synthesized and are presented in Table 1.

TABLE 1.

Literature review table.

Authors, publication year Study design and purpose Measurement, analysis and sample Results, alpha diversity Results, beta diversity Results, community structure
Kimmel et al., 2019 Prospective pilot, human cohort study Population: Human participants recruited in 1st or 2nd trimester. 2 SSRI-exposed participants had lower alpha diversity than all others and were excluded from analyses as outliers. N/A N/A
Results reported in a published conference abstract Sample sizes: 30, 4 SSRI-exposed
Collection: 16s rRNA sequencing, stool
Treatment: N/A
Purpose: “To assess tryptophan, kynurenine and serotonin in relation to microbial composition in a cohort of perinatal women enriched for women with psychiatric history of depression and/or anxiety” Analysis: Alpha diversity—Chao1, Shannon, PD whole tree, and observed species methods. Beta diversity—weighted UniFrac.
Ramsteijn et al., 2020 Prospective, controlled experiment, animal model Purpose: “To examine the hypothesis that depressive-like symptoms and antidepressant treatment during pregnancy and lactation affect the maternal microbiome and its functional capacity” Population: Genetic rat model of maternal vulnerability. Rats subjected to early life stress (sMV) or control handling (cMV). sMV or cMV rats treated with fluoxetine (FLX) or vehicle (Veh) during pregnancy and lactation. Alpha diversity was higher in sMV dams pre-treatment with FLX or Veh (p < .05). sMV-FLXand sMV-Veh dams differed by PCoA during pregnancy and lactation (p < .05, p = .001). During Pregnancy: FLX dams had lower Bacteroides relative abundance than Veh dams (p < .001).
cMV-FLX dams had a lower relative abundance of Bacteroides than the cMV-Veh dams (p < .01).
Sample sizes:
cMV-Veh 11 Interaction between FLX treatment and sMV noted during lactation (p < .05).
sMV-Veh 8 sMV-FLX dams had higher Prevotetta than sMV-Veh dams (p < .01).
cMV-FLX7
sMV-FLX6
Collection: cMV-FLX had higher relative abundance of Ruminococcus than the cMV-Veh (p < .05).
Weekly fecal samples collected for 16s rRNA sequencing (V4) at GD0, GD7, GD14, L2, L7, L14, and L21
sMV-FLX had higher Ruminococcus than the sMV-Veh dams (p < .001).
Treatment: From gestational day1 (GD1) to lactation day 21 (LD21), the dams received 10 mg/kg FLX or vehicle by oral gavage.
Lactation:
Analysis: Interaction between FLX and sMV on Prevotetta abundance (p < .01)
Alpha diversity—Shannon diversity index. sMV-FLX dams had higher Prevotetta relative abundance than sMV-Veh (p < .01) and cMV-FLX (p < .05).
Beta diversity—PCoA of weighted UniFrac distances.
Association between experimental condition an OTUs was determined using a machine-based learning algorithm Random Forests.
Interaction between FLX and sMV may exist (p < .05).
sMV-FLX dams had higher relative abundanceof Ruminococcus than sMV-Veh dams (p < .05).
Vuong et al., 2021 Prospective, controlled experiment, animal model Purpose: To investigate “the effects of maternal SSRI treatment on fetal neurodevelopment and to further evaluate roles for the maternal gut microbiome in modulating observed responses to SSRIs” Population: SPF mice treated with saline (SPF + Veh), SPF mice treated with fluoxetine (SPF + FLX), SPF mice pretreated with antibiotics and treated with saline (ABX + Veh), and SPF mice pretreated with antibiotics and treated with fluoxetine (ABX + FLX). Maternal treatment with fluoxetine did not produce statistically significant effects on alpha diversity. Maternal treatment with fluoxetine did not have any observed effect on beta diversity measures. Maternal treatment with fluoxetine resulted in increased Lachnospiraceae COE1 (GD8.5 p = .008, GD11.5 p = .005, GD14.5 p = .039), Btautia and Lachnoctostridium (GD6.5 p = .036, GD8.5 p = .033, GD14.5 p = .03, G11.5 p = .03).
Sample sizes: n = 24, 6/group.
Collection: Fecal samples for 16s rRNA sequencing (V4) were collected from SPF + Veh and SPF + FLX mice on GD3.5, GD6.5, GD8.5, GD11.5, and GD14.5.
Lachnospiraceae UCG-006 was elevated in the fluoxetine treated dams prior to fluoxetine administration (GD3.5 p = .04, GD8.5 p = .02).
Treatment: Male and female mice in ABX groups orally gavaged with vancomycin (50 mg/kg), neomycin (100 mg/kg), and metronidazole (100 mg/kg) 2x/daily for 7 days with subsequent maintenance on ampicillin (1 mg/mL) in drinking water.
Females received 8 days (GD7.4–14.5) of 10 mg/kg fluoxetine by gavage or vehicle (saline).
Analysis: Alpha diversity—Shannon’s diversity index Beta diversity—PCoA of weighted UniFrac distances
Taxonomic comparisons were analyzed by Kruskal-Wallis test with Tukey’s post hoc test.
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Note: Table represents a summary of the data synthesized by reviewers K.D.-S. and H.F.

Abbreviations: PCoA, principal coordinates analysis; PD, phylogenetic diversity; SPF, specific-pathogen free.

3 |. RESULTS

3.1 |. Source search and screen

Search of the PubMed, Web of Science, and Scopus databases plus Google Scholar (gray literature) returned a total of 2235 publications for review. Of these 2235 publications, 813 were identified as duplicates and excluded, leaving 1423 for a title and abstract screen. During the first-round title and abstract screen, 1417 articles were identified as irrelevant and excluded, and six remained for full-text review. Ultimately, three sources met inclusion criteria following full review and were included in the synthesis.

3.2 |. Sources meeting inclusion criteria

Of the three included sources, two were experiments conducted in rodents (Ramsteijn et al., 2020; Vuong et al., 2021) and one was human subjects research (Kimmel et al., 2019). Notably, the human subjects research was reported in a published conference abstract in which the reporting of methodology was limited. The two experiments conducted in rodents were published in peer-reviewed journals. While all 3 sources investigated the effects of perinatal SSRI exposure on the maternal gut microbiome, none of the sources included inquiry into any potential effects on the infant gut microbiome. Sample sizes were modest, ranging between 24 and 32 animals, and there were 30 human subjects, four of whom were SSRI exposed (Kimmel et al., 2019; Ramsteijn et al., 2020; Vuong et al., 2021). Notably, these sample sizes may not provide the necessary statistical power to conclusively determine potentially complex relationships between exposure timing, stress, and effect on the gut microbiome in animal or human populations. The following synthesis exists to assess the current state of evidence, and any resulting inferences should be interpreted with careful consideration of these limitations. A detailed summary and comparison of sources and results are available in Table 1.

3.3 |. Alpha diversity

The effects of SSRI exposure on maternal alpha diversity of the gut microbiome may vary by perinatal stage and in the presence of a depressive or stress-induced model. While one study found that maternal treatment with fluoxetine did not affect maternal alpha diversity during pregnancy (Vuong et al., 2021), others report mixed degrees of influence during pregnancy and lactation (Kimmel et al., 2019; Ramsteijn et al., 2020). In a rodent model, fluoxetine exposure during pregnancy and lactation was found to affect alpha diversity of the maternal gut microbiome during lactation and the influence was dependent on maternal stress (fluoxetine × maternal stress interaction) with maternal stress and fluoxetine exposure together resulting in a lower alpha diversity than fluoxetine exposure alone (Ramsteijn et al., 2020). Additionally, a human subjects study found that out of four taking SSRIs, two had such low levels of serotonin and alpha diversity that they were excluded from analyses as outliers (Kimmel et al., 2019).

3.4 |. Beta diversity

The influence of SSRI exposure on beta diversity of the maternal gut microbiome may also vary by perinatal stage (antepartum or postpartum) and whether the study included an exposure to stress. Researchers conducting a rodent study in the absence of stress redundant found that maternal treatment with fluoxetine did not have any observed effect on beta diversity measures during pregnancy (Vuong et al., 2021). In contrast, another study reports that fluoxetine treatment of maternal rodents exposed to a stress protocol resulted in distinct beta diversity profiles when compared to controls during pregnancy and lactation (Ramsteijn et al., 2020).

3.5 |. Community composition

The effects of perinatal SSRI exposure on community composition of the maternal gut microbiome may be dependent on perinatal stage and exposure to a model of stress or depression. In a rodent study that only examined the effect of SSRI exposure during pregnancy and in the absence of maternal stress, fluoxetine exposure was associated with an increase in Blautia, Lachnoclostridium, and Lachnospiraceae COE1 (Vuong et al., 2021). In contrast, another rodent study found that fluoxetine exposure during pregnancy and in the absence of stress is associated with a lower relative abundance of Bacteroides and higher Ruminococcus (Ramsteijn et al., 2020). Those treated with fluoxetine and subjected to stress had higher Prevotella and Ruminococcus during pregnancy (Ramsteijn et al., 2020). During lactation, mothers exposed to stress and fluoxetine had higher relative abundance of Prevotella than mothers exposed to fluoxetine or stress alone (Ramsteijn et al., 2020). Those exposed to combination of stress and fluoxetine treatment also had higher levels of Ruminococcus than those who were stressed and vehicle treated (Ramsteijn et al., 2020).

4 |. DISCUSSION

The results of this scoping review suggest that SSRI exposure during pregnancy and lactation may affect the alpha and beta diversity as well as individual taxa of the maternal gut microbiome, but that the available evidence is extremely limited with the majority of findings coming from experiments conducted in animal models (Ramsteijn et al., 2020; Vuong et al., 2021). Notably, despite the growing public health crisis surrounding perinatal mood disorders (The Joint Commission, 2023) and the increasing use of SSRI antidepressants in perinatal populations (Petersen et al., 2021), we found only three sources to inform our question regarding the influence of SSRI exposure on microbial communities in mothers during pregnancy and lactation and none to address the effect on the infant gut microbiome from birth to weaning or 1 year of life. Interestingly, we did find one source that describes an association between perinatal SSRI exposure and changes to the infant gut microbiome in adult rodents, although it did not meet our inclusion criteria (Law & Holloway, 2014). Our findings point strongly to a gap in existing literature and a need for further studies that determine the effects of perinatal SSRI exposure on the gut microbiome of both mothers and infants. Other insights include that model design may be key to producing conclusive, clinically relevant, and reproducible results.

Timing of gestational SSRI exposure is variable and critically important to interpretation of study findings. The rodent study reporting SSRI influence on gut microbiome diversity began treatment at GD 1 (gestational day 1; beginning of the pregnancy) and continued until lactation day 21 (LD 21; weaning). In contrast, the rodent study that reports no SSRI effect on gut microbiome diversity started treatment at GD 8.5 and continued until GD 14.5 (mid-pregnancy), ultimately resulting in 39 versus 8 days of exposure. It is possible that SSRI exposure for 8 days is not long enough to observe changes that may eventually occur. Notably, the only human study did not disclose length of SSRI exposure for each participant but it would likely have been greater than 8 days, considering that in human populations SSRIs are taken for a period of weeks to months before therapeutic effect is expected. While the rodent gestation is significantly shorter than that of humans, effects of SSRI exposure on bacterial populations may occur according to bacterial lifecycle rather than host gestation. Ultimately, the effect of an SSRI on the gut microbiome may require consideration of both the host gestational (rodent, human, etc.) and bacterial life cycle.

Whether SSRI exposure occurs during pregnancy, lactation, or throughout both periods may also affect findings and ultimately, any observed effects on maternal and infant health. An established body of evidence describes the maternal gut microbiome as highly dynamic throughout pregnancy and lactation (Edwards et al., 2017). Changes in the maternal gut microbiome during this period may be related to metabolic fluctuation and inflammatory processes known to occur during pregnancy (Edwards et al., 2017). A rodent model included in this review confirms this concept and provides further evidence for a highly dynamic maternal gut microbiome (Ramsteijn et al., 2020). For this reason, it is not only important to understand how SSRI exposure may affect taxa at each stage but also to determine how SSRI exposure may affect features of the dynamic gut microbial transition that occurs during pregnancy and lactation. Furthermore, we are lacking studies of only lactational exposure, which represents a tremendous gap in our understanding of how SSRIs prescribed specifically for postpartum depression may affect gut microbiome composition and ultimately, maternal and infant health.

Modeling of mood disorders such as anxiety or depression is an additional consideration relevant to investigating effects of SSRI exposure on the maternal and infant gut microbiome. Results of our synthesis show that rodent models with and without exposure to stress have produced disparate results (Ramsteijn et al., 2020; Vuong et al., 2021). Although stress and depression represent distinct concepts, exposure to stress is recognized as a precursor to primary episodes of depression and is frequently used in animal modeling of depressive states (Acikgoz et al., 2022). Because depression itself has been shown to affect adult and infant gut microbiome composition (Chen et al., 2021; Galley et al., 2023; Rodriguez et al., 2021), consideration of the depressive gut microbiome may be key to understanding the complexities of SSRI exposure and the gut microbiome in human populations. While animal studies modeling SSRI exposure alone offer proof of principle that SSRI exposure has the potential to alter the maternal gut microbiome, models of stress or depression may offer the most translational value as mood disorders are a prerequisite for SSRI therapy in human populations. Those conducting this research with human participants may also consider that SSRI-exposed people may also experience varying degree of symptom breakthrough, potentially affecting gut microbiome composition, and that SSRI-related changes in the gut microbiome may contribute to therapeutic efficacy.

Additional considerations include the potential for different SSRI medications to exert distinct effects on the maternal and infant gut microbiome or other health outcomes. Sertraline, citalopram, and fluoxetine are the most commonly prescribed SSRIs during pregnancy (Bandoli et al., 2020). All rodent studies included in this synthesis used the SSRI fluoxetine, and the only human study did not report which specific SSRI was prescribed. It is possible that treatment with distinct SSRI medications was a factor in findings that only two of the four human subjects had distinctly low alpha diversity (Kimmel et al., 2019). Given the diverse chemical structure of SSRIs, disparate effect on the maternal or infant gut microbiome is plausible. In fact, research including two SSRI medications as interventions has found differences in effects on pregnancy-related outcomes, such as pregnancy rate or the success rate for becoming pregnant (Domingues et al., 2022). This synthesis highlights an additional gap in research, that there is no evidence to support our understanding of the effects of SSRIs on the gut microbiome with any SSRI medication other than fluoxetine. Efforts to further the state of the science should design studies to generate evidence using all SSRI medications approved for use during pregnancy and lactation.

Attention to perinatal care practices such as antibiotic therapy may also be relevant to understanding the relationship between SSRI exposure, the maternal gut microbiome, and infant health. Antibiotic exposure occurs commonly during pregnancy and lactation for a variety of reasons including group B strep prophylaxis, premature or prolonged rupture of membranes, or the treatment of infections during lactation (like mastitis). One rodent study included in our synthesis found that maternal treatment with antibiotics altered gene expression patterns in the fetal brain that were distinct from changes observed in conditions of SSRI exposure alone (Vuong et al., 2021). Because antibiotic exposure is widely acknowledged for its effects on gut microbiome composition, it is possible that the combination of antibiotic and SSRI therapy may exert distinct effects on the gut microbiome or have distinct effects on maternal and infant health outcomes related to gut microbiome diversity and composition. Future studies on the effects of perinatal SSRI exposure on offspring may consider including clinical aspects of perinatal care in the study design.

Limitations of our synthesis include the possibility that additional evidence exists that was not uncovered through our methodology or that did not meet our inclusion criteria. Furthermore, synthesis of studies evaluating gut microbiome composition using 16s rRNA sequencing may be limited by potential variation introduced through the variety of bioinformatic techniques that are commonly used to determine differential abundance (Cappellato et al., 2022). Additionally, one of the three total sources and the only human subjects study did not provide beta diversity or community composition metrics specific to SSRI exposure, potentially because results were published in a conference abstract. Due to the lack of published evidence on this topic, our review team also chose to include all sources of evidence, although some provided a limited description of experimental parameters. Implications include that our findings must be interpreted in recognition of this sparse availability of information and with acknowledgment that the current state of the science is preliminary. Variation in study design, including model system (human vs. animal), timing of exposure, and stress effects, also suggests that findings should be interpreted with recognition of these limitations, considering the complexity of these factors and the sparse availability of sources. Ultimately, this lack of evidence has informed our findings, indicating a gap in current literature and highlighting the need for further, well-designed, and controlled trials.

5 |. CONCLUSION

There is a severe shortage of available evidence to inform scientists, providers, and childbearing people regarding the effects of perinatal SSRI exposure on gut microbial communities in mothers and infants. Future research should include other SSRIs commonly prescribed in perinatal populations, such as citalopram and sertraline. Research teams may also consider the use of animal models to further investigate the effects of SSRI exposure on the maternal and infant gut microbiome under the presence and absence of stress. Any results should be translated through conduct of human subjects studies to determine clinical relevance. Use of additional omics technologies such as metabolomics may also serve to connect observed changes in gut microbiome diversity and composition with functional assessments that link exposure-related changes to health outcomes. This information would be of high value to the clinical population and serve to better inform providers and childbearing people in making informed decisions regarding treatment of mood disorders during pregnancy and lactation.

Supplementary Material

Supplementary Information

ACKNOWLEDGMENTS

The authors acknowledge the support of Mary Hitchcock in this study.

Footnotes

CONFLICT OF INTEREST STATEMENT

The authors declare no conflicts of interest.

SUPPORTING INFORMATION

Additional supporting information can be found online in the Supporting Information section at the end of this article.

DATA AVAILABILITY STATEMENT

Data sharing is not applicable to this article as no new data were created or analyzed in this study.

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Supplementary Information
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