Symposium 23: Microbiome Pathways in Early-Life Inequity: Stress, Development, and the Biological Embedding of Adversity

Overview Abstract

Title: Microbiome Pathways in Early-Life Inequity: Stress, Development, and the Biological Embedding of Adversity
Michelle D. Graf1,2*, Sarah C. Vogel3, Naomi Gancz4

1. Virginia Commonwealth University School of Nursing
2. University of North Carolina at Chapel Hill
3. University of Massachusetts Boston
4. University of California, Los Angeles
*Denotes presenter

Understanding how early-life inequities become biologically embedded requires integrative, cross-disciplinary perspectives. The gut microbiome has emerged as a dynamic interface between the environment, nutrition, and maternal and child health, offering new pathways for discovery and innovation. This session brings together diverse and interdisciplinary perspectives to examine how the microbiome reflects and shapes responses to adversity across development. First, Dr. Michelle Graf will present work positioning the infant gut microbiome as a marker of biobehavioral risk, focusing on links with brain development and eating behaviors. Next, Dr. Sarah Vogel will discuss studies of maternal stress and breast milk biomarkers in relation to infant microbial trajectories, highlighting maternal–infant biological synchrony under conditions of stress. Finally, Naomi Gancz will share findings on the relationship between basal ganglia iron and gut microbial composition in adversity-exposed youth, revealing microbiome-brain connections that extend into later development. Together, these presentations illustrate how integrating microbiome science with measures of stress biology, nutrition, and neurodevelopment can generate innovative approaches to understanding and mitigating the health impacts of early adversity.

Topic 1
Title: The Infant Gut Microbiome as a Biobehavioral Marker of Risk: Linking Prenatal Stress, Brain Development, and Eating Behaviors

Michelle D. Graf1,2*, Sarah C. Vogel3, Nicolas Murgeuitio2,3, Mary Kimmel5, Cathi Propper1

1. Virginia Commonwealth University School of Nursing
2. University of North Carolina at Chapel Hill
3. University of Massachusetts Boston
4. Emory University
5. University of Washington at St. Louis

Introduction: Infancy is a critical window for neurodevelopment, during which biological and environmental exposures interact to shape trajectories of health and risk. The gut microbiome has emerged as a biobehavioral marker of early developmental processes, linking prenatal stress, neonatal microbiome, and early neurodevelopment. Understanding these pathways is essential for uncovering mechanisms through which inequities and adversity may become biologically embedded.

Methods: Across three projects, we examined the microbiome as a developmental risk marker. (1) In a cross-species systematic review, we synthesized evidence on associations between prenatal stress and infant gut microbiome composition. (2) In a longitudinal cohort (N = 60), we tested links between neonatal microbiome composition at 2 weeks and child eating behaviors at 36 months using whole genome sequencing and multivariate regression. (3) In a neuroimaging cohort (N = 88), we assessed associations between neonatal microbiome features and brain structure (insula, amygdala, thalamus, ACC) using 3T MRI and random forest regressions.

Results: The review identified consistent evidence that maternal stress during pregnancy alters infant microbial composition, with downstream implications for neurodevelopment. In the cohort studies, specific microbial taxa (e.g., Streptococcus, Staphylococcus, Clostridium) predicted emotional undereating, overeating, and food fussiness in early childhood, while microbial diversity, taxonomy (e.g., Veillonella, Enterobacter), and functional gene pathways were associated with structural variation in brain regions involved in emotional and interoceptive processing. Complementary findings also show that neonatal brain structure of the insula and putamen may predict later eating behaviors in a sex-specific manner, underscoring the interconnected roles of microbiome, brain development, and behavior in early risk pathways.

Conclusion: Together, these findings position the infant gut microbiome as both a reflection of early exposures and stress-related risk and a potential driver of biobehavioral outcomes, linking prenatal stress, microbial development, brain structure, and eating behaviors. By integrating systematic evidence and developmental cohorts, this presentation highlights microbiome–brain–behavior pathways, illuminating mechanisms that may help explain the biological embedding of early-life inequities.

Topic 2
Title: Maternal postpartum stress predicts composition of breastmilk and infant gut microbiome

Sarah C. Vogel1*, Scott C. Thomas2, Bradley Susskind3, Fangxi Xu2, Deepak Saxena2, Moriah Thomason4, Natalie H. Brito5
1. University of Massachusetts Boston
2. New York University College of Dentistry
3. Rutgers New Jersey School of Medicine
4. New York University Langone Medical Center
5. Columbia University

Introduction: Increasing rates of postpartum stress and mental illness, and subsequent implications for child development, are growing societal concerns. An expanding body of research has suggested that one mechanism by which maternal psychosocial stress impacts infant development is via differences in early microbial exposures and colonization. In this study, we seek to add to this growing body of research by examining associations between maternal psychosocial stress and the microbial composition of breastmilk and infant stool in a longitudinal sample of infants and their mothers.

Methods: We collected maternal self-reports of perceived stress, postpartum depression, and social support at 6 months postpartum. Breastmilk samples were collected at 6 and 12 months postpartum and sequenced using 16S RNA gene sequencing to characterize the breastmilk microbiome. Infant stool samples were collected at 12 months and sequenced using Shotgun metagenomic sequencing. We used MaAslin2 models to identify genera of bacteria in breastmilk and infant stool significantly related to maternal psychosocial wellbeing, calculated the Shannon, Simpson, and Chao1 indices to capture alpha diversity, and performed principal coordinates analyses on Bray-Curtis distances to assess associations between maternal stress and between-subjects differences in breastmilk and stool composition (beta diversity).

Results: Higher maternal stress predicted an enrichment of Rothia in breastmilk at 6 months (b=1.35, q=.06). Higher maternal depression was associated with an enrichment in Cutibacterium (b=1.08, q=.14). Higher maternal social support was associated with lower Chao1 diversity (r=-.23, p=.01) and depletions in Rothia (b=-1.33, q=.06), Granulicatella (-1.14, q=.08), Prevotella (b=-1.02, q=.08), Streptococcus (b=-1.15, q=.08), and Veillonella (b=-1.35, q=.08) in breastmilk at 6 months. Higher maternal depression correlated with shifts in composition of the infant gut microbiome (beta diversity; r=.24, p=.05), such that higher depression was associated with enrichment of Blautia, Enterocloster, and Anaerotruncus and depletion of Lactobacillus and Bifidobacterium in the infant gut at 12 months.

Discussion: We found that maternal psychosocial wellbeing at 6 months postpartum correlated with concurrent differences in the microbial composition of breastmilk and predicted differences in infant gut microbiome composition 6 months later. Connections between microbial communities in breastmilk and infant stool will be presented. These findings deepen our scientific understanding of how stress shapes the transfer of microbes between mother and infant and add to a growing body of literature pointing towards the microbiome as a mechanism by which stress shapes infant development.

Topic 3
Title: Basal Ganglia Iron Associations with Gut Microbiome in Adversity-Exposed Children and
Adolescents
Gancz, N.N.,1* Silvers, J.A.,1 Choy, T. 2 , VanTieghem, M.,3 Uhlemann, A-C.,3 Park, H.,3 Parr A.,4 Callaghan, B.L.1

1 University of California, Los Angeles
2 University of California, Riverside
3 Columbia University
4 University of Pittsburgh

Introduction: Early interpersonal adversity (IA; significant separation from or maltreatment by
a caregiver or other close individual) leads to increased mental health risk. This risk is
attributable in part to alterations in the development of dopaminergic brain circuits, and of the
gut microbiome; however, the relationship between these brain circuits and the gut microbiome
in youth is not well understood. Importantly, iron is a key nutrient both for gut microbiome
health and for dopamine synthesis, and iron accumulation in the basal ganglia has been closely
linked to dopamine availability. Thus, we examined the relationship between the gut microbiome
and basal ganglia iron accumulation in IA-exposed and unexposed youth.

Methods: We calculated an index of basal ganglia tissue iron, time-averaged and normalized
T2* (nT2*w), using resting-state and task-based fMRI scans in N = 82 children and adolescents
aged 5-18. About half the sample had previously experienced IA and, of the full sample, N = 48
youth also contributed stool, which was sequenced using 16S amplicon target gene sequencing,
and from which we derived Shannon’s alpha diversity index (an index of microbiome richness
and evenness) and genus-level bacterial abundance. All analyses controlled for age and sex, and
microbiome analyses at the genus level were subject to multiple comparison correction at a false
discovery rate threshold of q < .05.

Results: IA youth had significantly lower basal ganglia iron levels (p < .05). Additionally,
among IA-exposed youth, but not comparison youth, higher Shannon’s diversity was
significantly correlated with lower iron estimates (p < .05), as was higher abundance of several
Oscillospiraceae genera (q < .05). Conversely, several genera in the Lachnospiraceae and
Ruminococcaceae families displayed interaction effects in the opposite direction, i.e. they were
associated with higher estimated tissue iron in the IA, but not comparison, group (q N .05).

Discussion: We found that youth with a history of IA exposure had significantly lower iron
accumulation than comparison youth. Among IA-exposed youth, those whose microbiomes had
higher Shannon’s diversity or higher abundance of certain Oscillospiraceae genera had lower
iron levels, whereas those whose microbiomes had higher abundance of certain Lachnospiraceae
and Ruminococcaceae genera had higher iron levels. One possible explanation is that a
microbiome profile high in Lachnospiraceae and Ruminococcaceae and low in Oscillospiraceae
and Shannon’s diversity enhances host iron absorption. Our findings suggest that iron may be an
important component of the gut-brain axis in youth exposed to early interpersonal adversities.

Presenter - Michelle Graf, Virginia Commonwealth University
Presenter - Sarah Vogel, PhD, MA, University of Massachusetts Boston
Presenter - Naomi Gancz, University of California, Los Angeles