Doctoral Dissertation Improvement: Social change, parasite exposure and immune dysregulation: An evolutionary medicine approach

最近的两个假说--卫生学假说和消失的微生物区系假说--认为工业化国家过敏和自身免疫性疾病的急剧上升源于接触病原体的减少。这些假设假设了当代生活方式和人类物种进化生物学之间的不匹配。与生活在欠发达国家的人相比，生活在美国等发达国家的人接触寄生虫和细菌的机会减少了，肠道微生物组成的总体变化也减少了。这些变化似乎导致免疫刺激减少，对过敏和自身免疫性疾病的易感性增加，而这些在非西方人群中几乎是不存在的。本论文由俄勒冈大学博士生塔拉·塞邦(Tara Cepon)在詹姆斯·斯诺德格拉斯博士的指导下，在来自亚马孙厄瓜多尔的觅食园艺人口Shuar中测试了卫生学和消失的微生物区系假说，他们目前正在经历与融入市场经济相关的快速但不平衡的文化变化。该项目考察了经历不同程度的市场参与和相关社会变化的三个地理上分离的Shuar社区之间的社会/生活方式因素、肠道寄生虫组成、免疫功能和调节失调之间的关系。通过家庭访谈、粪便样本的显微镜和分子分析以及免疫功能的生物标记物，本项目将阐明寄生虫的暴露模式和人类作为寄生居民生态系统的作用，以及这些居民对免疫发展和功能的贡献。这项研究还将通过将必要的注意力集中在环境变化如何影响传染病和自身免疫性疾病的流行来促进对文化变化对健康影响的了解。除了这些贡献，这项研究还对公共卫生政策、社区推广、国际科学伙伴关系和教育产生了重要影响。这项研究增加了我们对市场相关变化对舒阿尔以及其他经历文化变化的人群健康差异的影响的理解。此外，它有可能通过确定在实施减少传染病和慢性病负担的政策时针对的生活方式因素，提供可用于改善当地和全球健康的见解。最后，该项目将培养一名女科学家，并为本科生提供研究机会。

Two recent hypotheses--the Hygiene Hypothesis and the Disappearing Microbiota Hypothesis--argue that the dramatic rise in allergies and autoimmune disorders in industrialized nations stems from decreased exposure to pathogens. These hypotheses posit a mismatch between contemporary lifestyles and the evolved biology of the human species. People living in developed nations such as the United States are experiencing reduced exposure to parasitic worms and bacteria, as well as overall changes to the microbial composition of the gut, compared to individuals living in less developed nations. These changes appear to be resulting in decreased immune stimulation and an increased vulnerability to allergy and autoimmune diseases, which are nearly absent in non-Western populations. The present dissertation study by doctoral student Tara Cepon (University of Oregon), under the supervision of Dr. James Snodgrass, tests both the Hygiene and Disappearing Microbiota Hypotheses among the Shuar, a forager-horticulturalist population from Amazonian Ecuador who are currently experiencing rapid yet uneven cultural change related to integration into the market-based economy. The project examines relationships among social/lifestyle factors, intestinal parasite composition, and immune function and dysregulation among three geographically separated Shuar communities experiencing different degrees of market involvement and related social change. Through household interviews, microscopic and molecular analyses of fecal samples, and biomarkers of immune function, the present project will shed light on patterns of parasite exposure and the role of humans as ecosystems for our parasitic residents, as well as the contribution that these residents make to immune development and function. This study also will advance knowledge of the health effects of cultural change by focusing needed attention on how environmental shifts affect infectious and autoimmune disease prevalence. Beyond these contributions, this study has important implications for public health policy, community outreach, international science partnerships, and education. The research increases our understanding of the effects of market-related changes on health variation among Shuar and, by extension, other populations undergoing cultural change. Further, it has the potential to provide insights that can be used for improving local and global health by identifying lifestyle factors to target when implementing policies to reduce infectious and chronic disease burden. Finally, this project will train a female scientist and will provide research opportunities for undergraduates.