Assessing Changes to the Lower GI Tract Microbiome in Response to Neglect-related Early Life Stress Exposure

dc.creatorChoe, Jamieen_US
dc.creatorDonkor, Michaelen_US
dc.creatorZhang, Yanen_US
dc.creatorGorham, Isabelleen_US
dc.creatorAllen, Michaelen_US
dc.creatorPhillips, Nicoleen_US
dc.creatorJones, Harlanen_US
dc.descriptionResearch Appreciation Day Award Winner - School of Biomedical Sciences, 2024 Department of Microbiology, Immunology & Genetics (Cell Biology, Immunology & Microbiology) Award - 1st Placeen_US
dc.descriptionResearch Appreciation Day Award Winner - Texas College of Osteopathic Medicine, 2024 Medical Student Government Association Best of DO/PhD Dual Degree Studentsen_US
dc.description.abstractGrowing evidence supports exposure to early life stress (ELS) is associated with alterations in the developing immune system and increases the risk for chronic health conditions. It is widely understood that alterations to the gut microbiome can occur from exposure to various environmental factors, including diet and stress. Early life malnutrition is a form of neglect-related ELS that refers to states of both under- and over-nutrition in which a child may have insufficient intake of one or more nutrients due to an imbalanced diet. Malnutrition during childhood is a public health concern with significant health ramifications. Recent research shows the gut microbiome is intimately involved with immune system development—especially during early life when the immune system is being trained. In the present study, we use a modified version of the maternal separation with early weaning (MSEW) model to study the impact of physical neglect and malnutrition on the gut microbiome in mice. Conditions of neglect-related stress were simulated based on scheduled dam-pup separation (physical neglect) and a high carbohydrate early-wean diet (malnutrition). C57BL/6J mice were bred in-house and ELS pups were subjected to: (1) daily dam-pup separation on postnatal days (PD) 2-13 and/or (2) early weaning (EW) to a high carbohydrate diet on PD14-21. All tissues and stool samples were collected on PD21 for analysis. Pups exposed to MSEW or EW alone were assessed separately. 16S rRNA gene sequencing revealed the neglect-related ELS condition, as described under the present model, led to significant shifts in the predominate species in the lower GI tract microbial community. ELS-mediated shifts included increased Bacteroides and Enterococcus and were accompanied by decreased Lachnospiraceae. RTqPCR of bilateral adrenal glands revealed gene expression changes in key enzymes for stress response pathways, namely those implicated in the synthesis of adrenal glucocorticoids. These results demonstrate ELS-mediated dysbiosis can be observed at PD21 under the present model. Our findings at the PD21 timepoint reveal acute changes to the gut microbiome in the context of ELS and characterizes the baseline microbial community in the lower GI tract.en_US
dc.description.sponsorshipNational Institutes of Health/National Institute on Aging (NIA) T32 AG020494; National Institute on Minority Health and Health Disparities (NIMHD) 5U54MD006882-10en_US
dc.titleAssessing Changes to the Lower GI Tract Microbiome in Response to Neglect-related Early Life Stress Exposureen_US