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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Nutr.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Nutrition</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Nutr.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">2296-861X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnut.2026.1776398</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Systematic Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Prebiotics, probiotics, and synbiotics and maternal mental health during pregnancy and postpartum period: a systematic review</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Mart&#x00ED;n-Pel&#x00E1;ez</surname>
<given-names>Sandra</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1401262"/>
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<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; original draft" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-original-draft/">Writing &#x2013; original draft</role>
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</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Mart&#x00ED;n-delosReyes</surname>
<given-names>Luis Miguel</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/3330733"/>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Formal analysis" vocab-term-identifier="https://credit.niso.org/contributor-roles/formal-analysis/">Formal analysis</role>
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<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Writing &#x2013; review &#x0026; editing" vocab-term-identifier="https://credit.niso.org/contributor-roles/writing-review-editing/">Writing &#x2013; review &#x0026; editing</role>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Cano-Ib&#x00E1;&#x00F1;ez</surname>
<given-names>Naomi</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/1152792"/>
<role vocab="credit" vocab-identifier="https://credit.niso.org/" vocab-term="Funding acquisition" vocab-term-identifier="https://credit.niso.org/contributor-roles/funding-acquisition/">Funding acquisition</role>
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</contrib>
</contrib-group>
<aff id="aff1"><label>1</label><institution>Department of Preventive Medicine and Public Health, Faculty of Medicine, University of Granada</institution>, <city>Granada</city>, <country country="es">Spain</country></aff>
<aff id="aff2"><label>2</label><institution>CIBER Epidemiolog&#x00ED;a y Salud P&#x00FA;blica (CIBERESP), Instituto de Salud Carlos III (ISCIII)</institution>, <city>Madrid</city>, <country country="es">Spain</country></aff>
<aff id="aff3"><label>3</label><institution>Instituto de Investigaci&#x00F3;n Biosanitaria de Granada (ibs.GRANADA)</institution>, <city>Granada</city>, <country country="es">Spain</country></aff>
<author-notes>
<corresp id="c001"><label>&#x002A;</label>Correspondence: Luis Miguel Mart&#x00ED;n-delosReyes, <email xlink:href="mailto:luismiguel@ugr.es">luismiguel@ugr.es</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-02-17">
<day>17</day>
<month>02</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2026</year>
</pub-date>
<volume>13</volume>
<elocation-id>1776398</elocation-id>
<history>
<date date-type="received">
<day>27</day>
<month>12</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>20</day>
<month>01</month>
<year>2026</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>01</month>
<year>2026</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2026 Mart&#x00ED;n-Pel&#x00E1;ez, Mart&#x00ED;n-delosReyes and Cano-Ib&#x00E1;&#x00F1;ez.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Mart&#x00ED;n-Pel&#x00E1;ez, Mart&#x00ED;n-delosReyes and Cano-Ib&#x00E1;&#x00F1;ez</copyright-holder>
<license>
<ali:license_ref start_date="2026-02-17">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>Depression and anxiety are common during pregnancy and postpartum, affecting both mothers&#x2019; 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.</p>
</sec>
<sec>
<title>Aim</title>
<p>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.</p>
</sec>
<sec>
<title>Methods</title>
<p>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.</p>
</sec>
<sec>
<title>Results</title>
<p>Of the 1,401 records identified, four RCTs (<italic>n&#x202F;=</italic>&#x202F;1,342 women) met the inclusion criteria. All RCTs evaluated probiotics interventions, none assessed prebiotics or synbiotics. Of four, two RCTs using <italic>Lactobacillus rhamnosus</italic> HN001, <italic>Limosilactobacillus reuteri</italic> PBS072 and <italic>Bifidobacterium breve</italic> reported small but significant reductions in depressive symptoms [Edinburgh Postnatal Depression Scale, MD&#x202F;=&#x202F;&#x2212;1.2; 95% CI (&#x2212;2.3, &#x2212;0.1)] and anxiety symptoms [State&#x2013;Trait Anxiety Inventory-6: MD&#x202F;=&#x202F;&#x2212;1.0; 95% CI (&#x2212;1.9, &#x2212;0.2); <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05)] during pregnancy. One RCT showed significantly lower depressive scores in the intervention group at day 45 (mean 9.0&#x202F;&#x00B1;&#x202F;4.8 vs. 12.1&#x202F;&#x00B1;&#x202F;5.9; <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001) and day 90 (7.0&#x202F;&#x00B1;&#x202F;3.3 vs. 10.8&#x202F;&#x00B1;&#x202F;6.2; <italic>p</italic>&#x202F;&#x003C;&#x202F;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.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>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.</p>
</sec>
<sec>
<title>Systematic review registration</title>
<p>PROSPERO, identifier (CRD42024576678).</p>
</sec>
</abstract>
<kwd-group>
<kwd>anxiety disorder</kwd>
<kwd>depressive disorder</kwd>
<kwd>microbiota</kwd>
<kwd>postpartum</kwd>
<kwd>pregnancy</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was received for this work and/or its publication. This study was funded by Project &#x201C;PI23/01866&#x201D;, funded by Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union.</funding-statement>
</funding-group>
<counts>
<fig-count count="3"/>
<table-count count="2"/>
<equation-count count="0"/>
<ref-count count="53"/>
<page-count count="10"/>
<word-count count="6108"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Nutrition, Psychology and Brain Health</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1">
<label>1</label>
<title>Introduction</title>
<p>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 (<xref ref-type="bibr" rid="ref1">1</xref>). These disorders are linked to adverse outcomes for both maternal well-being and infant development (<xref ref-type="bibr" rid="ref2">2</xref>). Although pharmacotherapy is a mainstay treatment, concerns about maternal and fetal safety have increased interest in alternative approaches (<xref ref-type="bibr" rid="ref3">3</xref>). Non-pharmacological interventions, such as cognitive-behavioural therapy and exercise, have shown potential benefits (<xref ref-type="bibr" rid="ref4">4</xref>). Recent studies suggest a relationship between maternal mental health disorders and the gut microbiota through the gut&#x2013;brain axis (<xref ref-type="bibr" rid="ref5">5</xref>). The gut microbiota influences the central nervous system via autonomic, hormonal and immune pathways and has been associated with psychological disorders (<xref ref-type="bibr" rid="ref6 ref7 ref8">6&#x2013;8</xref>). Pregnancy induces physiological changes in gut microbiota composition (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref10">10</xref>), while environmental disturbances may negatively affect maternal biology and mental health (<xref ref-type="bibr" rid="ref11">11</xref>, <xref ref-type="bibr" rid="ref12">12</xref>). Maternal microbiota perturbations may influence offspring development through microbiota-derived fetal programming and early-life microbial transmission from mother to infant (<xref ref-type="bibr" rid="ref13">13</xref>, <xref ref-type="bibr" rid="ref14">14</xref>).</p>
<p>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 (<xref ref-type="bibr" rid="ref15 ref16 ref17 ref18">15&#x2013;18</xref>). Despite growing interest in microbiota-targeted interventions, evidence on their role in primary prevention of maternal mental health problems remains limited (<xref ref-type="bibr" rid="ref19 ref20 ref21">19&#x2013;21</xref>). 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 (<xref ref-type="bibr" rid="ref19">19</xref>, <xref ref-type="bibr" rid="ref20">20</xref>). Moreover, their methodological quality assessed using AMSTAR-2 was low (<xref ref-type="supplementary-material" rid="SM1">Supplementary material 1</xref>). These limitations justify the need for an updated systematic review to evaluate current evidence and identify research gaps.</p>
<p>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.</p>
</sec>
<sec sec-type="methods" id="sec2">
<label>2</label>
<title>Methods</title>
<p>This systematic review was carried out in accordance to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement (<xref ref-type="bibr" rid="ref22">22</xref>). A protocol for this review was registered in the International prospective register of systematic reviews (PROSPERO ID: CRD42024576678).</p>
<sec id="sec3">
<label>2.1</label>
<title>Search strategy and selection criteria</title>
<p>A comprehensive bibliographic search was conducted (<xref ref-type="supplementary-material" rid="SM1">Supplementary material 2</xref>) 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.</p>
<p>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.</p>
<p>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 <xref ref-type="supplementary-material" rid="SM1">Supplementary material 2</xref>) 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.</p>
<p>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 (<xref ref-type="bibr" rid="ref23">23</xref>). 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 (<xref ref-type="supplementary-material" rid="SM1">Supplementary material 3</xref>).</p>
</sec>
<sec id="sec4">
<label>2.2</label>
<title>Data extraction</title>
<p>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.</p>
<p>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.</p>
<p>The quality of the included studies was assessed using the Risk of Bias 2 (ROB2) tool (<xref ref-type="bibr" rid="ref24">24</xref>). 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 &#x201C;low risk,&#x201D; &#x201C;some concern,&#x201D; or &#x201C;high risk&#x201D; 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).</p>
</sec>
<sec id="sec5">
<label>2.3</label>
<title>Evidence synthesis</title>
<p>We tabulated the findings and constructed graphs as appropriate. Due to small number of studies, statistical synthesis was not performed.</p>
</sec>
</sec>
<sec sec-type="results" id="sec6">
<label>3</label>
<title>Results</title>
<p>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 (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>PRISMA 2020 flow diagram for the systematic reviews including searches of databases, registers, and other sources.</p>
</caption>
<graphic xlink:href="fnut-13-1776398-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">PRISMA flow diagram summarizing study identification and selection for a systematic review: out of 1,401 records identified, 516 duplicates were removed, 885 records screened, 874 excluded, 11 assessed for eligibility, 7 excluded for specified reasons, and 4 studies included in the review.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec7">
<label>4</label>
<title>Characteristics and quality of included studies</title>
<p>The included studies were carried out in New Zealand (<xref ref-type="bibr" rid="ref25">25</xref>), Finland (<xref ref-type="bibr" rid="ref26">26</xref>), Iran (<xref ref-type="bibr" rid="ref27">27</xref>), and Italy (<xref ref-type="bibr" rid="ref28">28</xref>). The publication dates ranged from 2016 to 2023. The total number of participants varied from 60 (<xref ref-type="bibr" rid="ref27">27</xref>) to 439 (<xref ref-type="bibr" rid="ref26">26</xref>), 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&#x202F;weeks, and the participants&#x2019; ages ranged from 16 (<xref ref-type="bibr" rid="ref25">25</xref>) to 50&#x202F;years (<xref ref-type="bibr" rid="ref28">28</xref>) (<xref ref-type="table" rid="tab1">Table 1</xref>). The four RCTs included probiotics in the interventions. The probiotic strains used were <italic>Lactobacillus rhamnosus</italic> HN001 (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>), <italic>Bifidobacterium animalis ssp. lactis</italic> 420 (<xref ref-type="bibr" rid="ref26">26</xref>), <italic>Limosilactobacillus reuteri</italic> PBS072 (<xref ref-type="bibr" rid="ref28">28</xref>), <italic>Bifidobacterium breve</italic> BB077 (<xref ref-type="bibr" rid="ref28">28</xref>), <italic>Lactobacillus acidophilus</italic> La-5 and <italic>Bifidobacterium lactic</italic> Bb-12 (<xref ref-type="bibr" rid="ref27">27</xref>). The probiotic daily dose varied from 4&#x202F;&#x00D7;&#x202F;10<sup>9</sup>&#x202F;CFU (<xref ref-type="bibr" rid="ref28">28</xref>) to 4.8&#x202F;&#x00D7;&#x202F;10<sup>10</sup>&#x202F;CFU (<xref ref-type="bibr" rid="ref27">27</xref>), administered in capsules with the exception of one study, which used yogurt as probiotic vehicle (<xref ref-type="bibr" rid="ref27">27</xref>). Intervention duration ranged from 4&#x202F;weeks (<xref ref-type="bibr" rid="ref27">27</xref>) to 48&#x202F;weeks (<xref ref-type="bibr" rid="ref25">25</xref>), and occurred during pregnancy only (<xref ref-type="bibr" rid="ref27">27</xref>), both pregnancy and postpartum (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>) or only postpartum (<xref ref-type="bibr" rid="ref28">28</xref>). From the four studies, three investigated mental health as primary outcome (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref28">28</xref>). The mean intervention follow-up rated from 12 to 24&#x202F;months (<xref ref-type="table" rid="tab2">Table 2</xref>).</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Characteristics of the studies.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Author, year</th>
<th align="left" valign="top" rowspan="2">Country</th>
<th align="left" valign="top" rowspan="2">RCT design</th>
<th align="center" valign="top" colspan="3">Population</th>
</tr>
<tr>
<th align="left" valign="top">Sample Size (intervention/Control)</th>
<th align="left" valign="top">Inclusion criteria</th>
<th align="left" valign="top">Exclusion criteria</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Hulkkonen et al. (<xref ref-type="bibr" rid="ref26">26</xref>)</td>
<td align="left" valign="top">Finland</td>
<td align="left" valign="top">Double-blind, 2&#x00D7;2 factorial parallel groups</td>
<td align="left" valign="top"><italic>N&#x202F;=</italic>&#x202F;439 (split into 4 groups)</td>
<td align="left" valign="top">1) Age: Not specified<break/>2) Type of pregnancy: Singleton<break/>3) GW: &#x2264; 18&#x202F;weeks of gestation<break/>4) BMI: &#x2265; 25 Kg/m2<break/>5)Absence of chronic diseases (except for asthma and allergies)</td>
<td align="left" valign="top">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&#x202F;months postpartum were excluded from the postpartum analyses</td>
</tr>
<tr>
<td align="left" valign="top">Mirghafourvand et al. (<xref ref-type="bibr" rid="ref27">27</xref>)</td>
<td align="left" valign="top">Iran</td>
<td align="left" valign="top">Triple-blind, two parallel groups</td>
<td align="left" valign="top"><italic>N&#x202F;=</italic>&#x202F;60 (30/30)</td>
<td align="left" valign="top">1) Age: &#x003E;18&#x202F;years<break/>2) GW: between 24&#x2013;28 weeks of gestation<break/>4) Women suffered from constipation<break/>5) Being literate and willing to participate in the study</td>
<td align="left" valign="top">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</td>
</tr>
<tr>
<td align="left" valign="top">Slykerman et al. (<xref ref-type="bibr" rid="ref25">25</xref>)</td>
<td align="left" valign="top">New Zealand</td>
<td align="left" valign="top">Double-blind, two center</td>
<td align="left" valign="top"><italic>N&#x202F;=</italic>&#x202F;423 (212/211)</td>
<td align="left" valign="top">1) Age: &#x003E;16&#x202F;years<break/>2) GW: between 24&#x2013;28&#x202F;weeks of gestation<break/>4) English-speaking<break/>5) Planning to breastfeed<break/>6) They or the unborn child&#x2019;s biological father had a history of asthma, hay fever or eczema requiring medication</td>
<td align="left" valign="top">Women were excluded from the study if aged &#x003C; 16&#x202F;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</td>
</tr>
<tr>
<td align="left" valign="top">Vicariotto et al. (<xref ref-type="bibr" rid="ref28">28</xref>)</td>
<td align="left" valign="top">Italy</td>
<td align="left" valign="top">Double-blind, multicenter, two parallel groups</td>
<td align="left" valign="top"><italic>N&#x202F;=</italic>&#x202F;190 (95/95)</td>
<td align="left" valign="top">1) Age 18&#x2013;50&#x202F;years old<break/>2) Women in the first trimester postpartum<break/>3) Good general health condition<break/>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.)<break/>5) Subjects aware of this study&#x2019;s procedures and having signed an informed consent form</td>
<td align="left" valign="top">1) Subjects who do not meet the inclusion criteria<break/>2) Subjects considered as not adequate to participate in this study by the investigator<break/>3. Subjects with known or suspected sensitization to one or more test formulation ingredients<break/>4) Adult protected by law (under control or hospitalized in public or private institutions for reasons other than research or incarcerated)<break/>5) Subjects not able to communicate or cooperate with the investigator due to problems related to language, mental retardation, or impaired brain function<break/>6) Subjects suffering from other psychiatric disorders such as schizophrenia, other psychotic disorders, bipolar disorder, or substance use disorder<break/>7) Subjects with serious physical illnesses or mental disorders<break/>8) Subjects with significant risk of infanticide according to the investigator&#x2019;s assessment<break/>9) Subjects taking herbal remedies or psychotropic drugs intended for depression and taken within the last 2&#x202F;weeks prior to baseline or during this study<break/>10) Subjects receiving counselling or psychological therapies at baseline or during this study</td>
</tr>
</tbody>
</table>
</table-wrap>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Summary of main results.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Author, year</th>
<th align="center" valign="top" colspan="4">Intervention</th>
<th align="left" valign="top">Control&#x002A;&#x002A;</th>
<th align="center" valign="top" colspan="4">Mental health outcomes</th>
</tr>
<tr>
<th align="left" valign="top">Type</th>
<th align="left" valign="top">Bacterial strains</th>
<th align="left" valign="top">Dose</th>
<th align="left" valign="top">Duration</th>
<th align="left" valign="top">Type</th>
<th align="left" valign="top">Type</th>
<th align="left" valign="top">Test</th>
<th align="left" valign="top">Period</th>
<th align="left" valign="top">Results</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Hulkkonen et al. (<xref ref-type="bibr" rid="ref26">26</xref>)</td>
<td align="left" valign="top">Fish oil and Probiotics&#x002A;</td>
<td align="left" valign="top"><italic>Lactobacillus rhamnosus</italic> HN001 and <italic>Bifidobacterium animalis ssp. lactis</italic> 420</td>
<td align="left" valign="top">1 capsule/day containing 10^10 CFU per strain</td>
<td align="left" valign="top">Enrolment (&#x2264;18 GW) to 6&#x202F;months postpartum</td>
<td align="left" valign="top">Placebo for the probiotics: capsule containing microcrystalline cellulose<break/>Placebo for fish oil: capsule containing medium chain fatty acids</td>
<td align="left" valign="top">Depressive and anxiety symptoms</td>
<td align="left" valign="top">EPDS (Ediburgh Posnatal Depression Scale)<break/>SCL-90 (Symptom Checklist-90)</td>
<td align="left" valign="top">Early pregnancy and late pregnancy and at three, six and 12&#x202F;months postpartum</td>
<td align="left" valign="top">No differences among intervention groups and placebo</td>
</tr>
<tr>
<td align="left" valign="top">Mirghafourvand et al. (<xref ref-type="bibr" rid="ref27">27</xref>)</td>
<td align="left" valign="top">Probiotics</td>
<td align="left" valign="top"><italic>Bifidobacterium lactic</italic> (Bb-12) and <italic>Lactobacillus acidophilus</italic> (La-5)</td>
<td align="left" valign="top">300 grams of yogurt containing 4.8&#x202F;&#x00D7;&#x202F;10^10 CFU (combined strains), 100&#x202F;g x three times a day</td>
<td align="left" valign="top">Four weeks</td>
<td align="left" valign="top">Conventional yogurt, identical appearance</td>
<td align="left" valign="top">Quality of life</td>
<td align="left" valign="top">SF-36 (Quality of life questionnaire)</td>
<td align="left" valign="top">At baseline and at the end of week 6</td>
<td align="left" valign="top">No differences among intervention group and placebo</td>
</tr>
<tr>
<td align="left" valign="top">Slykerman et al. (<xref ref-type="bibr" rid="ref25">25</xref>)</td>
<td align="left" valign="top">Probiotic</td>
<td align="left" valign="top"><italic>Lactobacillus rhamnosus</italic> HN001</td>
<td align="left" valign="top">1 capsule/day containing 6&#x202F;&#x00D7;&#x202F;10^9 CFU</td>
<td align="left" valign="top">Enrolment until birth and, from birth up till 6 months post-birth whilst breastfeeding</td>
<td align="left" valign="top">Capsules containing corn-derived maltodextrin, identical appearance</td>
<td align="left" valign="top">Depressive and anxiety symptoms</td>
<td align="left" valign="top">EPDS (Ediburgh Posnatal Depression Scale)<break/>STAI-6 (State Trait Anxiety Inventory-6)</td>
<td align="left" valign="top">Mothers (baseline and after 6&#x202F;months or 12&#x202F;months after delivery) completed the surveys based on how they remember they felt when their child was 1&#x2013;2&#x202F;months old</td>
<td align="left" valign="top">Depression: The intervention group reported significantly lower scores (7.7&#x202F;&#x00B1;&#x202F;5.4) than placebo (9.0&#x202F;&#x00B1;&#x202F;6.0).<break/>Mean difference &#x2212;1.2 (&#x2212;2.3, &#x2212;0.1), <italic>p</italic>&#x202F;=&#x202F;0.037<break/>Anxiety: The intervention group also reported lower scores (12.0&#x202F;&#x00B1;&#x202F;4.0 vs. 13.0&#x202F;&#x00B1;&#x202F;4.3). Mean difference: &#x2212;1.0 (&#x2212;1.9, &#x2212;0.2), <italic>p</italic>&#x202F;=&#x202F;0.014</td>
</tr>
<tr>
<td align="left" valign="top">Vicariotto et al. (<xref ref-type="bibr" rid="ref28">28</xref>)</td>
<td align="left" valign="top">Probiotics and plus multivitamin food supplement</td>
<td align="left" valign="top"><italic>Limosilactobacillus reuteri</italic> PBS072 and <italic>Bifidobacterium breve</italic> BB077</td>
<td align="left" valign="top">1 capsule/day containing 4&#x202F;&#x00D7;&#x202F;10^9 CFU/day (2&#x202F;&#x00D7;&#x202F;10^9 CFU for each strain)</td>
<td align="left" valign="top">90&#x202F;days</td>
<td align="left" valign="top">The same capsules without the probiotic strains (identical appearance)</td>
<td align="left" valign="top">Postpartum depression symptoms</td>
<td align="left" valign="top">EPDS (Ediburgh Posnatal Depression Scale)</td>
<td align="left" valign="top">45&#x202F;days after the beginning of the treatment and final visit (i.e., 90&#x202F;days after the beginning of the treatment)</td>
<td align="left" valign="top">At day 45, the intervention group showed a significantly lower mean score (9.0&#x202F;&#x00B1;&#x202F;4.8) compared to the control group (12.1&#x202F;&#x00B1;&#x202F;5.9) (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.001). On day 90, the intervention group showed a significantly lower mean score (7.0&#x202F;&#x00B1;&#x202F;3.3) compared to the control group (10.8&#x202F;&#x00B1;&#x202F;6.2) (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.001).</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>&#x002A;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. &#x002A;&#x002A; In all studies, the duration and dose of placebos was identical to the intervention.</p>
</table-wrap-foot>
</table-wrap>
<p>Of the included studies, one was classified as a high risk (<xref ref-type="fig" rid="fig2">Figure 2</xref>), the remaining 3 studies were classified as moderate. Among the ROB2 domains (<xref ref-type="fig" rid="fig3">Figure 3</xref>), the most frequent critical weakness identified was the risk of bias in the selection of the reported outcome.</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Risk of bias assessment of the included studies across individual domains and overall judgment.</p>
</caption>
<graphic xlink:href="fnut-13-1776398-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Risk of bias summary table for four studies showing five bias domains with color-coded judgments: green plus for low risk, yellow minus for some concerns, and red X for high risk. Slykerman, 2017 had high risk in D4 and overall; other studies mostly had some concerns or low risk across domains. Domains and judgment explanations provided below the table.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>Summary of overall risk of bias across domains for the included studies.</p>
</caption>
<graphic xlink:href="fnut-13-1776398-g003.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Horizontal bar graph titled "Overall risk of bias" shows six bias domains with proportions colored green for low risk, yellow for some concerns, and red for high risk; a legend explains each color.</alt-text>
</graphic>
</fig>
<sec id="sec8">
<label>4.1</label>
<title>Primary outcomes</title>
<p>Depressive (<italic>n&#x202F;=</italic>&#x202F;3) and anxiety (<italic>n&#x202F;=</italic>&#x202F;2) symptoms were the most frequently assessed outcomes, measured using tools such as the Edinburgh Postnatal Depression Scale (EPDS) (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref28">28</xref>), the State Trait Anxiety Inventory-6 (STAI-6) (<xref ref-type="bibr" rid="ref25">25</xref>) and the Symptom Checklist-90 (SCL-90) (<xref ref-type="bibr" rid="ref26">26</xref>). In addition, one study measured quality of life using the quality-of-life questionnaire (SF-36) (<xref ref-type="bibr" rid="ref27">27</xref>), which assesses aspects such as emotional problems, emotional well-being and related domains (<xref ref-type="table" rid="tab2">Table 2</xref>).</p>
<p>Regarding depressive or anxiety symptoms during pregnancy, one study (<xref ref-type="bibr" rid="ref26">26</xref>) found not statistically significant differences between intervention <italic>Lactobacillus rhamnosus</italic> HN001 plus <italic>Bifidobacterium animalis ssp. lactis</italic> 420 and control groups, although minor variations were observed at 12&#x202F;months of follow-up in EPDS test scores between the intervention groups containing fish oil and placebo versus probiotics and placebo (MD&#x202F;=&#x202F;&#x2212;1.12, <italic>p</italic>&#x202F;=&#x202F;0.039). In contrast, another study (<xref ref-type="bibr" rid="ref25">25</xref>) reported significant reductions in depression mean differences (MD) scores in the intervention group (<italic>Lactobacillus rhamnosus</italic> HN001) compared to the control [MD&#x202F;=&#x202F;&#x2212;1.2 95% CI (&#x2212;2.3, &#x2212;0.1)] and anxiety mean scores [MD&#x202F;=&#x202F;&#x2212;1.0 95% CI (&#x2212;1.9, &#x2212;0.2)]. Regarding postpartum depression, one study (<xref ref-type="bibr" rid="ref28">28</xref>) reported that at day 45, the intervention group (<italic>Limosilactobacillus reuteri</italic> PBS072 plus <italic>Bifidobacterium breve</italic> BB077) showed a significantly lower mean score (9.0&#x202F;&#x00B1;&#x202F;4.8) compared to the control group (12.1&#x202F;&#x00B1;&#x202F;5.9) (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.001) and at day 90 (7.0&#x202F;&#x00B1;&#x202F;3.3 vs. 10.8&#x202F;&#x00B1;&#x202F;6.2, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001) (<xref ref-type="table" rid="tab2">Table 2</xref>). Another study (<xref ref-type="bibr" rid="ref27">27</xref>) showed not significant differences between intervention (<italic>Lactobacillus acidophilus</italic> La-5 plus <italic>Bifidobacterium animalis subsp. lactis</italic> Bb-12) and control groups regarding quality of life.</p>
</sec>
<sec id="sec9">
<label>4.2</label>
<title>Secondary outcomes</title>
<p>From the 4 studies included in the review, only one (<xref ref-type="bibr" rid="ref28">28</xref>) reported information about the secondary outcomes. Using the Breastfeeding Self-Efficacy Scale&#x2014;Short Form (BSES-SF), they found that 45 and 90&#x202F;days after the beginning of the intervention, breastfeeding quality and the baby&#x2019;s crying/fussing significantly improved in the probiotic group. At 45&#x202F;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&#x202F;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 (<italic>p</italic>&#x202F;&#x003C;&#x202F;0.001).</p>
</sec>
</sec>
<sec sec-type="discussion" id="sec10">
<label>5</label>
<title>Discussion</title>
<p>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 (<xref ref-type="bibr" rid="ref19">19</xref>, <xref ref-type="bibr" rid="ref20">20</xref>). 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 (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>) others found no significant effects on mental health outcomes or quality of life (<xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref27">27</xref>), in line with previous systematic reviews showing mixed results (<xref ref-type="bibr" rid="ref19 ref20 ref21">19&#x2013;21</xref>).</p>
<p>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.</p>
<p>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 (<xref ref-type="bibr" rid="ref29">29</xref>, <xref ref-type="bibr" rid="ref30">30</xref>). 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 (<xref ref-type="bibr" rid="ref31 ref32 ref33">31&#x2013;33</xref>). Nevertheless, because these secondary outcomes were reported in only one included trial, they should be interpreted cautiously and cannot be generalized.</p>
<p>Methodological heterogeneity likely explains these discrepancies, including wide variation in participant age (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref28">28</xref>), intervention duration (<xref ref-type="bibr" rid="ref27">27</xref>), probiotic strains and doses (<xref ref-type="bibr" rid="ref34">34</xref>), and outcome measures. Some strains, such as <italic>Lactobacillus rhamnosus</italic> HN001 showed promising effects (<xref ref-type="bibr" rid="ref25">25</xref>), but findings remain inconclusive due to limitations such as retrospective data collection and high dropout rates (<xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref35">35</xref>). Other strains demonstrated benefits in specific populations or contexts (<xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref36 ref37 ref38 ref39 ref40">36&#x2013;40</xref>), suggesting context- and strain-specific effects.</p>
<p>Additional limitations include lack of standardized dosing (<xref ref-type="bibr" rid="ref41">41</xref>), inadequate control of antibiotic use by participants in RCTs (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref28">28</xref>), reliance on self-reported adherence (<xref ref-type="bibr" rid="ref42">42</xref>, <xref ref-type="bibr" rid="ref43">43</xref>), high microbiota variability (<xref ref-type="bibr" rid="ref44">44</xref>, <xref ref-type="bibr" rid="ref45">45</xref>), heterogeneity in psychological instruments with varying validity (<xref ref-type="bibr" rid="ref25">25</xref>, <xref ref-type="bibr" rid="ref26">26</xref>, <xref ref-type="bibr" rid="ref46 ref47 ref48 ref49 ref50 ref51 ref52">46&#x2013;52</xref>) and absence of structured clinical interviews (<xref ref-type="bibr" rid="ref53">53</xref>). Together, these issues underscore the need for well-designed, standardized RCTs to clarify the role of probiotics in maternal mental health.</p>
<sec id="sec11">
<label>5.1</label>
<title>Strengths and limitations</title>
<p>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.</p>
<p>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.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="sec12">
<label>6</label>
<title>Conclusion</title>
<p>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.</p>
</sec>
</body>
<back>
<sec sec-type="author-contributions" id="sec13">
<title>Author contributions</title>
<p>SM-P: Conceptualization, Formal analysis, Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. LM-d: Formal analysis, Methodology, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. NC-I: Funding acquisition, Methodology, Supervision, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<ack>
<title>Acknowledgments</title>
<p>We thank Camila Higueras-Callej&#x00F3;n 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.</p>
</ack>
<sec sec-type="COI-statement" id="sec14">
<title>Conflict of interest</title>
<p>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.</p>
</sec>
<sec sec-type="ai-statement" id="sec15">
<title>Generative AI statement</title>
<p>The author(s) declared that Generative AI was not used in the creation of this manuscript.</p>
<p>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.</p>
</sec>
<sec sec-type="disclaimer" id="sec16">
<title>Publisher&#x2019;s note</title>
<p>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.</p>
</sec>
<sec sec-type="supplementary-material" id="sec17">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fnut.2026.1776398/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fnut.2026.1776398/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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<fn fn-type="custom" custom-type="edited-by" id="fn0001">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1523682/overview">Andrew C. Shin</ext-link>, Texas Tech University, United States</p>
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<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/610468/overview">Francesca Uberti</ext-link>, University of Eastern Piedmont, Italy</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2969122/overview">Parvathy Unnikrishnan</ext-link>, Amrita Vishwa Vidyapeetham University, India</p>
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