Social Isolation and Discrimination as Stressors Influencing Brain-Gut Microbiome Alterations among Filipino and Mexican American

摘要 肥胖是一个主要的公共健康问题，与多种疾病有关，如心脏病 还有糖尿病。先前的研究表明，社交压力可能通过以下途径增加肥胖风险 饮食和体力活动的改变。然而，目前还不完全清楚这些改变如何导致肥胖。 在这项研究中，我们研究了社会孤立和歧视的压力来源与饮食的关系 行为和饮食模式，以及这些行为如何影响脑-肠道-微生物组(BGM)轴。 我们先前的研究表明，BGM的改变在肥胖的发展中起着重要作用。 我们的研究重点是墨西哥和菲律宾女性，因为研究表明，她们会遇到很大的负担 肥胖以及暴露在社会压力之下。 我们将筛选和登记大约300名墨西哥和菲律宾妇女，然后提供 通过一项调查，营养师24小时召回食物，测量有关社会压力源的信息 人体测量学(例如腰围)、关于饮食和饮食行为的问卷数据，以及 关于体力活动的加速度计数据。粪便和血清以确定微生物相关指标(16sRNA 测序、鸟枪式元基因组学和代谢组学)和磁共振成像来评估延长的 奖励网络将会被收集。将使用先进的多元分析技术来整合来自 多个数据来源(神经成像、微生物组和代谢物概况、调查数据、饮食和 临床/行为数据)。这一分析将确定与种族和社会相关的独特差异 调节饮食行为和饮食模式的压力源，以及与肥胖有关的BGM轴。一个 像所建议的那样的集成系统调查方法是理解 导致肥胖的机制。进一步说明环境应激源如何“深入皮肤”的影响 并影响饮食行为和饮食模式，而BGM轴在解决健康差距方面非常重要 在种族群体和妇女中。这一前提指导着本提案的具体目标：目标A：我们将表型 应激源对肥胖患者大脑信号和饮食模式的影响。目标B：我们将对 应激源对肥胖患者肠道菌群及代谢产物的影响。目标C：我们将应用高级分析 技术，以确定民族差异的压力源对肥胖的BGM轴的影响。 这项研究的结果将提供关于一种可能的途径的新信息， 应激源影响与肥胖风险相关的行为、神经和微生物机制。它还将提供 关于两个未被研究的民族的BGM模式的新信息。从长远来看，这项研究可能会 建议可能的干预方法，以帮助减少肥胖和相关健康方面的不平等 有问题。

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.