ABSTRACT Obesity is a major public health problem that is related to a variety of illnesses, such as heart disease and diabetes. Prior research indicates that social stressors contribute to risk for obesity, possibly through alterations in diet and physical activity. However, it is not fully clear how these alterations contribute to obesity. In this study, we examine how the stressors of social isolation and discrimination are related to eating behaviors and dietary patterns, and further, how these behaviors affect the brain-gut-microbiome (BGM) axis. Our prior research has suggested that BGM alterations play an important role in the development of obesity. Our study focuses on Mexican and Filipina women because research shows that they encounter a high burden of obesity as well as exposure to social stressors. We will screen and enroll approximately 300 Mexican and Filipina women who will then provide information about social stressors via a survey, dietician-administered 24-hour food recall, measured anthropometrics (e.g. waist circumference), questionnaire data regarding diet and eating behaviors, and accelerometer data on physical activity. Stool and serum to determine microbial-related measures (16sRNA sequencing, shotgun metagenomics, and metabolomics), and MRI to assess brain alterations in the extended reward network will be collected. Advanced multivariate analytic techniques will be used to integrate data from multiple data sources (neuroimaging, microbiome and metabolite profiles, survey data, diet, and clinical/behavioral data). This analysis will determine the unique variance associated with ethnicity and social stressors in moderating eating behaviors and dietary patterns, and the BGM axis related to obesity. An integrated systems investigative approach such as the one proposed is a critical step to understanding the mechanisms contributing to obesity. Further the impact of how environmental stressors “get under the skin” and impact eating behaviors and diet patterns and the BGM axis is important in addressing health disparities in ethnic groups and in women. This premise guides the specific aims of this proposal: Aim A: We will phenotype the influence of stressors on brain signatures and eating patterns in obesity. Aim B: We will phenotype the influence of stressors on gut microbiome and metabolites in obesity. Aim C: We will apply advanced analytical techniques in order to determine ethnic differences in the influence of stressors on the BGM axis in obesity. The results of this study will provide novel information about a possible pathway whereby social stressors affect behavioral, neurological and microbiome mechanisms related to obesity risk. It will also provide new information in BGM patterns in two understudied ethnic groups. In the long term, this research may suggest possible approaches for intervention that may help reduce inequalities in obesity and related health problems.