{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/140817"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/140817","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"Microbial and Immune Signatures of Stress and Antidepressants Across Sex and Generations","abstract":"The gut, brain, and immune system form an integrated and dynamic network that shapes development and health outcomes across the lifespan. Increasing evidence indicates that this axis is highly sensitive to stress exposure, displays robust sex-dependent properties, and may transmit biological effects across generations. This dissertation investigated how variable stress or perinatal antidepressant exposure alters gut microbial composition, immune signaling, and behavioral phenotypes in a sex-specific and multigenerational manner. To address these questions, we utilized 16S rRNA or whole-genome shotgun metagenomic sequencing in tandem with behavioral assays and multiplex cytokine profiling in rat and mouse models of chronic stress or perinatal SSRI exposure. Across studies, we demonstrate that the gut microbiome exhibits innate sex differences that are present early in life and continue to diversify with age. Aging was associated with increased alpha diversity and marked shifts in microbial metabolic pathway representation as well as a reversal of the Firmicutes–Bacteroidota ratio. Chronic stress induced distinct microbial alterations in males and females, with males showing a greater magnitude and diversity of microbial alterations. We further observed that female offspring more closely mirrored the microbial community structure of their dams, and that perinatal citalopram treatment produced stronger and more persistent effects in female offspring than in males. These findings reveal that stress and antidepressant exposure interact with sex and developmental stage to shape gut microbial composition and immune function. Microbial alterations following stress appear context-dependent, serving either compensatory or maladaptive roles depending on biological state and environmental challenge. Collectively, this work advances our understanding of how the gut–brain–immune axis integrates life experience across sex and generations and highlights the microbiome as a dynamic mediator and potential therapeutic target in stress-related neuropsychiatric vulnerability.","abstract_html":"The gut, brain, and immune system form an integrated and dynamic network that shapes development and health outcomes across the lifespan. Increasing evidence indicates that this axis is highly sensitive to stress exposure, displays robust sex-dependent properties, and may transmit biological effects across generations. This dissertation investigated how variable stress or perinatal antidepressant exposure alters gut microbial composition, immune signaling, and behavioral phenotypes in a sex-specific and multigenerational manner. To address these questions, we utilized 16S rRNA or whole-genome shotgun metagenomic sequencing in tandem with behavioral assays and multiplex cytokine profiling in rat and mouse models of chronic stress or perinatal SSRI exposure. Across studies, we demonstrate that the gut microbiome exhibits innate sex differences that are present early in life and continue to diversify with age. Aging was associated with increased alpha diversity and marked shifts in microbial metabolic pathway representation as well as a reversal of the Firmicutes–Bacteroidota ratio. Chronic stress induced distinct microbial alterations in males and females, with males showing a greater magnitude and diversity of microbial alterations. We further observed that female offspring more closely mirrored the microbial community structure of their dams, and that perinatal citalopram treatment produced stronger and more persistent effects in female offspring than in males. These findings reveal that stress and antidepressant exposure interact with sex and developmental stage to shape gut microbial composition and immune function. Microbial alterations following stress appear context-dependent, serving either compensatory or maladaptive roles depending on biological state and environmental challenge. Collectively, this work advances our understanding of how the gut–brain–immune axis integrates life experience across sex and generations and highlights the microbiome as a dynamic mediator and potential therapeutic target in stress-related neuropsychiatric vulnerability.","abstract_has_math":false,"creators":["Kropp, Dawson Ryan"],"institution":"Virginia Tech","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Neuroscience","degree_department":"Neuroscience","school":null,"contributors":[],"advisors":[],"committee_chairs":["Hodes, Georgia E."],"committee_members":["Jarome, Timothy","Clinton, Sarah","Howe, William Matthew","Basso, Julia C."],"year":2026,"date_issued":"2026-01-14","date_published":"2026-01-14","updated_at":"2026-07-22T22:20:38Z","subjects":["Stress","Gut","Microbiome","Depression","Cytokine","Sequencing","Transcriptomics","Metagenomics"],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:45547"],"render_values":[{"text":"vt_gsexam:45547","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10919/140817","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Hodes, Georgia E."]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Jarome, Timothy","Clinton, Sarah","Howe, William Matthew","Basso, Julia C."]},{"key":"dc:contributor.department","label":"Department","values":["Neuroscience"]},{"key":"dc:creator","label":"Author","values":["Kropp, Dawson Ryan"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2026-01-15T09:01:33Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2026-01-15T09:01:33Z"]},{"key":"dc:date.issued","label":"Date","values":["2026-01-14"]},{"key":"dc:publisher","label":"Institution","values":["Virginia Tech"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Neuroscience"]},{"key":"thesis:degree_level","label":"Degree Level","values":["doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["Virginia Polytechnic Institute and State University"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Stress","Gut","Microbiome","Depression","Cytokine","Sequencing","Transcriptomics","Metagenomics"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["In Copyright"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://rightsstatements.org/vocab/InC/1.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:45547"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://hdl.handle.net/10919/140817"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The gut, brain, and immune system form an integrated and dynamic network that shapes development and health outcomes across the lifespan. Increasing evidence indicates that this axis is highly sensitive to stress exposure, displays robust sex-dependent properties, and may transmit biological effects across generations. This dissertation investigated how variable stress or perinatal antidepressant exposure alters gut microbial composition, immune signaling, and behavioral phenotypes in a sex-specific and multigenerational manner. To address these questions, we utilized 16S rRNA or whole-genome shotgun metagenomic sequencing in tandem with behavioral assays and multiplex cytokine profiling in rat and mouse models of chronic stress or perinatal SSRI exposure. Across studies, we demonstrate that the gut microbiome exhibits innate sex differences that are present early in life and continue to diversify with age. Aging was associated with increased alpha diversity and marked shifts in microbial metabolic pathway representation as well as a reversal of the Firmicutes–Bacteroidota ratio. Chronic stress induced distinct microbial alterations in males and females, with males showing a greater magnitude and diversity of microbial alterations. We further observed that female offspring more closely mirrored the microbial community structure of their dams, and that perinatal citalopram treatment produced stronger and more persistent effects in female offspring than in males. These findings reveal that stress and antidepressant exposure interact with sex and developmental stage to shape gut microbial composition and immune function. Microbial alterations following stress appear context-dependent, serving either compensatory or maladaptive roles depending on biological state and environmental challenge. Collectively, this work advances our understanding of how the gut–brain–immune axis integrates life experience across sex and generations and highlights the microbiome as a dynamic mediator and potential therapeutic target in stress-related neuropsychiatric vulnerability."]},{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["This dissertation explores how factors such as stress or antidepressant use can influence the community of microbes living in the gut, and how these effects differ between males and females and can even extend across generations. The gut plays a key role in digestion, the immune system, and communication with the brain. Because of this, changes to gut microbes may help explain why stress affects people differently and why some individuals are more vulnerable to anxiety, depression, or other stress-related health concerns. In this research, stress and antidepressant exposure were modeled in rodents to understand how these experiences shape the gut and immune system over time. We found that males and females naturally have different patterns of gut microbes, and these differences continue to change throughout life. Stress changed the gut in both sexes, but males showed larger and more widespread changes than females. We also observed that female offspring tended to inherit gut microbe patterns more similar to their mothers, suggesting that some stress-related biological effects may be passed from one generation to the next. When pregnant animals were treated with a commonly prescribed antidepressant, their female offspring showed stronger changes than males, indicating that early-life medication exposure may shape development in sex-specific ways. Overall, this work shows that the gut microbiome is deeply connected to how the body responds to stress and medication, and that these responses are influenced by biological sex and family history."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["ETD"]},{"key":"dc:title","label":"Title","values":["Microbial and Immune Signatures of Stress and Antidepressants Across Sex and Generations"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Hodes, Georgia E."],"dc:contributor.committeemember":["Jarome, Timothy","Clinton, Sarah","Howe, William Matthew","Basso, Julia C."],"dc:contributor.department":["Neuroscience"],"dc:creator":["Kropp, Dawson Ryan"],"dc:date.accessioned":["2026-01-15T09:01:33Z"],"dc:date.available":["2026-01-15T09:01:33Z"],"dc:date.issued":["2026-01-14"],"dc:description.abstract":["The gut, brain, and immune system form an integrated and dynamic network that shapes development and health outcomes across the lifespan. Increasing evidence indicates that this axis is highly sensitive to stress exposure, displays robust sex-dependent properties, and may transmit biological effects across generations. This dissertation investigated how variable stress or perinatal antidepressant exposure alters gut microbial composition, immune signaling, and behavioral phenotypes in a sex-specific and multigenerational manner. To address these questions, we utilized 16S rRNA or whole-genome shotgun metagenomic sequencing in tandem with behavioral assays and multiplex cytokine profiling in rat and mouse models of chronic stress or perinatal SSRI exposure. Across studies, we demonstrate that the gut microbiome exhibits innate sex differences that are present early in life and continue to diversify with age. Aging was associated with increased alpha diversity and marked shifts in microbial metabolic pathway representation as well as a reversal of the Firmicutes–Bacteroidota ratio. Chronic stress induced distinct microbial alterations in males and females, with males showing a greater magnitude and diversity of microbial alterations. We further observed that female offspring more closely mirrored the microbial community structure of their dams, and that perinatal citalopram treatment produced stronger and more persistent effects in female offspring than in males. These findings reveal that stress and antidepressant exposure interact with sex and developmental stage to shape gut microbial composition and immune function. Microbial alterations following stress appear context-dependent, serving either compensatory or maladaptive roles depending on biological state and environmental challenge. Collectively, this work advances our understanding of how the gut–brain–immune axis integrates life experience across sex and generations and highlights the microbiome as a dynamic mediator and potential therapeutic target in stress-related neuropsychiatric vulnerability."],"dc:description.abstractgeneral":["This dissertation explores how factors such as stress or antidepressant use can influence the community of microbes living in the gut, and how these effects differ between males and females and can even extend across generations. The gut plays a key role in digestion, the immune system, and communication with the brain. Because of this, changes to gut microbes may help explain why stress affects people differently and why some individuals are more vulnerable to anxiety, depression, or other stress-related health concerns. In this research, stress and antidepressant exposure were modeled in rodents to understand how these experiences shape the gut and immune system over time. We found that males and females naturally have different patterns of gut microbes, and these differences continue to change throughout life. Stress changed the gut in both sexes, but males showed larger and more widespread changes than females. We also observed that female offspring tended to inherit gut microbe patterns more similar to their mothers, suggesting that some stress-related biological effects may be passed from one generation to the next. When pregnant animals were treated with a commonly prescribed antidepressant, their female offspring showed stronger changes than males, indicating that early-life medication exposure may shape development in sex-specific ways. Overall, this work shows that the gut microbiome is deeply connected to how the body responds to stress and medication, and that these responses are influenced by biological sex and family history."],"dc:description.degree":["Doctor of Philosophy"],"dc:format.medium":["ETD"],"dc:identifier.other":["vt_gsexam:45547"],"dc:identifier.uri":["https://hdl.handle.net/10919/140817"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Stress","Gut","Microbiome","Depression","Cytokine","Sequencing","Transcriptomics","Metagenomics"],"dc:title":["Microbial and Immune Signatures of Stress and Antidepressants Across Sex and Generations"],"dc:type":["Dissertation"],"thesis:degree_discipline":["Neuroscience"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:20:38Z"}