Interactions between helminth colonization and the gut microbiota

摘要蠕虫感染影响人体免疫反应是公认的，但 机制尚未完全理解。我们假设蠕虫的影响可能是间接的 由感染期间肠道微生物群的改变介导。蠕虫和肠道微生物群都可以发挥 强大的全身免疫调节作用。蠕虫感染流行率的变化以及 微生物群可能是促成“卫生假说”的环境因素， 自身免疫性疾病的发病率。生态失调（微生物群落的失调）是 这是许多人类疾病的共同特征，尤其是那些具有炎症成分的疾病。 我们研究了寄生虫殖民化对马来西亚土著人微生物群的影响， “猩猩”我们的初步结果已经确定了微生物之间的拮抗关系 以类杆菌目或梭菌目群落为主的群落。梭菌的扩张 2型细胞因子（IL-4和IL-13）可以驱动类杆菌目群落， 杯状细胞分泌粘液。粘液可直接促进人梭菌的生长。使用 在小鼠模型中，我们可以证明梭菌菌株的混合物可以直接抑制类杆菌， 即使在没有寄生虫感染的情况下，我们假设， 通过蠕虫定殖的梭菌群落促进宿主内的抗炎反应;以及 来自Orang Asli的梭菌菌株在免疫调节方面比现有菌株更有效。 膳食和营养素摄入的影响以及蠕虫定植和细菌之间的相互作用 需要建立网络。为了验证这些想法，我们将评估Orang肠道微生物群的变化， 正在接受公共卫生驱虫计划的阿斯利人口。沿着饮食调查， 研究将提供寄生虫定植个体的纵向分析，以确定因果关系 蠕虫与肠道微生物群的关系最后，我们将从猩猩身上分离出细菌菌株， 并确定它们是否在小鼠中复制蠕虫的抗炎作用。 了解感染、营养、微生物群和微生物交叉所涉及的生理过程 炎症，可以促进生物标志物的发现，并确定新的干预策略，以改善 全球健康。我们的研究建立在Loke博士（纽约大学），Lim博士（纽约大学） Malaya），Cadwell博士（纽约大学）和Bonneau博士（纽约大学），具有寄生虫学，微生物群研究， 微生物学和免疫学，流行病学和实地研究，计算生物学和生物统计学。 实现上述目标将对生活在发展中国家和 国家，以及发达国家。

Abstract It is well established that helminth infections impact human immune responses, but the mechanisms are incompletely understood. We hypothesize that the impact of helminths could be indirectly mediated by alterations to the gut microbiota during infection. Both helminths and the gut microbiota can exert powerful systemic immunoregulatory effects. Changes to the prevalence of helminth infections and the microbiota may be environmental factors contributing towards the “hygiene hypothesis” and the rising incidence of autoimmune diseases in developed nations. Dysbiosis (dysregulation of microbial communities) is a common feature of many human diseases, especially those with an inflammatory component. We have studied the effects of helminth colonization on the microbiota of indigenous Malaysians, called the “Orang Asli”. Our preliminary results have identified an antagonistic relationship between microbial communities dominated by either Bacteroidales or Clostridiales communities. The expansion of Clostridiales over Bacteroidales communities can be driven by type 2 cytokines (IL-4 and IL-13), which promote increased mucus production by goblet cells. Mucus can directly promote the growth of human Clostridial strains. Using mouse models, we could demonstrate that a cocktail of Clostridial strains could directly inhibit a Bacteroides dominated community, even in the absence of helminth infections. We hypothesize that the expansion of Clostridiales communities by helminth colonization promotes anti-inflammatory responses within the host; and that Clostridiales strains from the Orang Asli are more potent at immune-regulation than existing strains. The effects of diet and nutrient intake and the interactions between helminth colonization and bacterial networks need to be established. To test these ideas, we will assess alterations to the gut microbiota of Orang Asli populations undergoing public health deworming programs. Along with dietary surveys, the proposed field studies will provide longitudinal analyses of helminth-colonized individuals to establish cause and effect relationships of helminths on the gut microbiota. Finally, we will isolate bacterial strains from the Orang Asli and determine whether they replicate the anti-inflammatory effects of helminths in mice. Understanding physiological processes involved in the intersection of infection, nutrition, microbiota and inflammation, could promote biomarker discovery and identify novel interventional strategies towards improving global health. Our study builds upon existing collaborations between Dr. Loke (NYU), Dr. Lim (University of Malaya), Dr. Cadwell (NYU) and Dr. Bonneau (NYU), with expertise in parasitology, microbiota studies, microbiology and immunology, epidemiology and field studies, computational biology and biostatistics. Accomplishment of the above goals will have important implications to individuals living in both developing countries as well as developed countries.