Integrating Gut Microbiota and Violence Exposure Metrics to Classify Psychological Distress in Middle-Aged Adults

Abstract Khalil Iktilat1,2, Gali Levin3, Michal Isacson1 Sondra Turjeman4, Roy Tzemah-Shahar5, Gila Gamliel4, Yoram Louzoun3, Omry Koren4 & Maayan Agmon*5 1Department of Gerontology, Faculty of Health and Social Welfare, University of Haifa, Haifa, Israel 2 Ramat Gan Academic College, Israel 3 Department of Mathematics, Bar-Ilan University, Bar-Ilan University, Israel 4 Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel 5 The Cheryl Spencer Institute for Nursing Research, Faculty of Health and Social Welfare, University of Haifa, Haifa, Israel Corresponding author Maayan Agmon Objectives Exposure to violence and psychological distress are positively correlated across diverse populations. Microbiota-gut-brain crosstalk research supports that the microbiota is affected by environmental stressors and may play a causative role in host mental state. Accordingly, we explored how the microbiota relates to violence exposure and distress levels in midlife, a key period when vulnerability to both chronic stress and aging-related mental health decline begins to emerge. Methods We characterized the fecal microbiota of a previously snowball-recruited Israeli-Muslim cohort (n=305, 40-65 yrs) exposed to increasing violence in the past decade and examined correlations with subjective reports of violence exposure and psychological distress focusing on a subset of bacterial taxa identified from a literature search. Then, we used machine learning to leverage microbiota profiles and violence exposure, classifying individuals into high- and low-distress categories. Results We identified unique microbial signatures associated with increasing violence exposure and distress. While some significantly associated bacteria were previously identified in the literature, many correlations were novel. Furthermore, microbial profiles associated with violence and distress were largely non-overlapping, yet we could classify participants into high- and low distress categories using a combination of microbiota and violence variables. The combined model outperformed those using only microbiota or demographics, but its overall classification accuracy remained modest (with a median area-under-the-curve of 0.595 (IQR 0.045). Discussion This research sheds light on the microbiota-gut-brain axis in the context of violence exposure and psychological distress in a population of adults in midlife, highlighting that exposure and distress are differentially associated with microbiota composition. These findings, together with better than average classification into distress classes based on the microbiome, suggest that holistic, context aware interventions may be relevant for preventative or proactive mental health interventions to support healthier aging. Keywords: microbiota-gut-brain axis, high-risk classification, community violence, public mental health