Prenatal Stress Induces Placental Dysfunction: The Role of Microbes, Inflammation, and Serotonin Helen Chen 1 , Adrienne Antonson 1 , Therese Rajasekera 1 , and Tamar Gur 1 1 Ohio State University, College of Medicine Background: Prenatal stress is deleterious to both mother and fetus and is associated with offspring neurodevelopmental deficits. There is emerging evidence that disruption of the maternal gut microbiome and subsequent immunomodulation and alteration of serotonergic metabolism is a potential mechanism by which prenatal stress affects neuro- development. However, the complex interplay between maternal microbes, inflammation, and serotonin at the maternal-fetal interface is unclear. In this study, germ-free and CCL2-/- mice were examined alongside wild type controls to investigate placental dysfunction following prenatal stress. Methods: Pregnant female C57BL/6 (WT), CCL2-/-, and germ-free (GF) mice were randomly assigned to the stressed or the non-stressed control group. The stressed group underwent restraint stress between embryonic days (E)10-E16. Placental tissue was collected on E17 for RT-PCR, ELISA, and LC/MS analyses of gene expression of serotonin metabolism-related genes and concentrations of chemokines and metabolites. Results: Prenatal stress led to an increase in the chemokine CCL2 in WT placentas (p<0.05), but not under GF conditions. Prenatal stress also elevated concentrations of tryptophan and serotonin in the WT placenta, which was abrogated in CCL2-/- and GF tissues (stress x genotype interaction, p<0.05), indi- cating the key role of maternal microbes and CCL2 in mediating intrauterine serotonergic dysfunction. However, stress did not alter expression of TPH1, which synthesizes serotonin from tryptophan, or MAOA, which breaks down se- rotonin, suggesting the changes in concentration are due to altered availability of metabolites from the maternal circulation. Conclusions: Overall, our findings suggest that PNS leads to serotonergic changes in the placenta in a CCL2- and microbe- dependent manner. Supported By: R21, K08 Keywords: Prenatal Stress, Inflammation, Gut Microbiome, Serotonin Probiotic-Induced Changes in Gut Microbial Composi- tion Relate to its Buffering Effect Against the Negative Consequences of Stress on Cognitive Performance Alejandro Arias Vasquez 1 , Mirjam Bloemendaal 1 , Joanna Szopinska-Tokov 1 , David Boverhof 2 , Silvia Papalini 2 , Franziska Michels 2 , Saskia van Hemert 3 , and Esther Aarts 2 1 Radboud University Medical Center Nijmegen, 2 Radboud University, Donders Institute for Brain Cognition and Behaviour, Centre for Cognitive Neuroimaging, 3 Winclove Probiotics Background: Probiotics affect emotional processing (including emotional memory and decision making), as well as reduce sensitivity for sad mood in humans. The mechanisms by which probiotics influence behavior and neurobiological measures may include the gut microbiota. However, evidence for the involvement of the gut microbiome in the effect of probiotics on stress-related cognitive performance is lacking in humans. Here, we asked whether the relative abundance of the gut microbiome is altered by probiotics and whether these changes are associated with behavioral and neurobiological variation. Methods: We isolated bacterial DNA from feces donated by healthy women volunteers before and after intervention with probiotics and sequenced the 16S rRNA gene. We assessed the effect of probiotics on gut microbial diversity measures and composition. We selected the genera showing an intervention effect to assess their relation with behavior and neurobiological measures. Results: Seven genera showed increased relative abundance after intervention. These genera are, mostly, plant degraders contributing to gut health. Relative abundance of Rumino- coccacceae_UCG-003 positively correlated with the buffering effect on working memory performance (rs(27)¼ .565, p¼ .002). Participants whose relative abundance of this taxa was increased after probiotics also had the strongest benefit of probiotics on working memory after stress. This effect was adjusted for relevant covariates and multiple comparisons. More importantly, this effect was not observed in the placebo group. Conclusions: Our results (in healthy volunteers) suggest that multispecies probiotics could exert a protective effect of cognitive performance (when measured under stress condi- tions) and that this effect is mediated by the gut microbial composition. Supported By: Top Sector Life Sciences & Health (LSH) PPP Allowance (Match Call), the Netherlands; Horizon 2020 - Research and Innovation Framework Programme, project number 728018 “Eat2beNICE” Keywords: Probiotics, Microbiome-Gut-Brain Axis, Working Memory Profiles of Longitudinal Treatment Response Hoarding Disorder Jessica Zakrzewski 1 , Scott Mackin 2 , Kevin L. Delucchi 2 , and Carol A. Mathews 3 1 University of Florida, 2 University of California, San Fran- cisco, 3 University of Florida Genetics Institute, University of Florida Background: Hoarding disorder (HD) is a highly impairing condition that effects between 2-6% of the population. The cur- rent standard of care for treatment of HD is cognitive behavioral therapy which has been shown to decrease symptoms between 12-37%. In this study we seek to determine longitudinal out- comes of clinician compared to peer-led treatment and under- stand if there are profiles related to treatment response. Methods: Longitudinal treatment response data was obtained for 181 individuals, 144 of whom completed neuro- psychological and clinical data at three timepoints: Biological Psychiatry May 1, 2020; 87:S134eS462 www.sobp.org/journal S325 Poster Abstracts Biological Psychiatry