Interactions between helminth colonization and the gut microbiota

蠕虫定植与肠道微生物群之间的相互作用

• 批准号: 10318081
• 负责人: Ken Hashigiwa Cadwell
• 金额: $ 66.03万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-01-02 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10318081
• 关键词: Anthelmintics; Anti-Inflammatory Agents; Antiinflammatory Effect; Archaea; Ascaris; Autoimmune Diseases; Bacteria; Bacteroides; Biometry; Blood; Classification; Collaborations; Communities; Complex; Computational Biology; Data; Developed Countries; Developing Countries; Diet; Environmental Risk Factor; Eukaryota; Genome; Germ-Free; Gnotobiotic; Goals; Goblet Cells; Growth; Helminths; Hookworms; Human; Hygiene; Immune; Immune response; Immunology; Incidence; Indigenous; Individual; Infection; Inflammation; Inflammatory; Inflammatory Response; Intake; Interleukin-13; Interleukin-4; Intervention; Intestines; Large Intestine; Lead; Malaysia; Malaysian; Mammals; Mediating; Metagenomics; Microbiology; Mucous body substance; Mus; Nutrient; Nutrition Surveys; Nutritional status; Parasites; Parasitology; Pharmacotherapy; Physiological Processes; Population; Prevalence; Production; Property; Public Health; Regulatory T-Lymphocyte; Resolution; Sampling; Shotguns; Small Intestines; Soil; Surveys; Taxonomy; Testing; Treatment Efficacy; Trichocephalus trichiura; Trichuris; Universities; Virus; bacterial community; biomarker discovery; commensal bacteria; cytokine; dietary; dysbiosis; epidemiology study; field study; global health; gut bacteria; gut inflammation; gut microbiota; helminth infection; host colonization; human disease; immunoregulation; improved; longitudinal analysis; metagenomic sequencing; microbial; microbial community; microbiota; mouse model; multidimensional data; novel; nutrition; programs

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.

摘要众所周知，蠕虫感染会影响人类的免疫反应，但 机制还没有完全被理解。我们假设蠕虫的影响可能是间接的 通过感染期间肠道微生物区系的变化来调节。蠕虫和肠道微生物群都可以发挥作用 强大的全身性免疫调节作用。蠕虫感染流行情况的变化和 微生物区系可能是促成“卫生假说”的环境因素。 发达国家自身免疫性疾病的发病率。生物失调(微生物群落的失调)是 这是许多人类疾病的共同特征，尤其是那些带有炎症成分的疾病。 我们研究了蠕虫殖民对马来西亚本土人微生物区系的影响，称为 “奥朗·阿斯利”我们的初步结果已经确定了微生物之间的拮抗关系 由拟杆菌科或梭状芽孢杆菌群落主导的群落。梭状芽胞杆菌的扩展 类杆菌群落可以由2型细胞因子(IL-4和IL-13)驱动，它们促进了 杯状细胞产生粘液。粘液可直接促进人源梭状芽胞杆菌的生长。vbl.使用 小鼠模型，我们可以证明梭状芽胞杆菌菌株的鸡尾酒可以直接抑制类杆菌 主导社区，即使在没有蠕虫感染的情况下也是如此。我们假设宇宙的扩张 通过蠕虫定植的梭状芽胞杆菌群落促进宿主内部的抗炎反应；以及 来自Orang Asli的梭状芽胞杆菌菌株比现有的菌株具有更强的免疫调节能力。 饮食和营养摄入量的影响及蠕虫定植与细菌的相互作用 需要建立网络。为了测试这些想法，我们将评估猩猩肠道微生物区系的变化 正在进行公共卫生驱虫计划的ASLI人群。与饮食调查一起，拟议的领域 研究将对寄生蠕虫的个体进行纵向分析，以确定因果关系。 肠道微生物区系中蠕虫的相互关系。最后，我们将从Orang Asli中分离出细菌菌株 并确定它们是否在小鼠身上复制了蠕虫的抗炎作用。 了解感染、营养、微生物区系和 炎症，可以促进生物标记物的发现，并确定新的干预策略以改善 全球健康。我们的研究建立在罗克博士(纽约大学)、林博士(纽约大学) 马来亚)、卡德韦尔博士(纽约大学)和博诺博士(纽约大学)，在寄生虫学、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。 上述目标的实现将对生活在这两个发展中的个人产生重要影响 既有发达国家，也有国家。

项目成果

Quantifying the Severity of Adverse Drug Reactions Using Social Media: Network Analysis.

• DOI: 10.2196/27714
• 发表时间: 2021-10-21
• 期刊: Journal of medical Internet research
• 影响因子: 7.4
• 作者: Lavertu A;Hamamsy T;Altman RB
• 通讯作者: Altman RB

Gut microbiome of helminth-infected indigenous Malaysians is context dependent.

• DOI: 10.1186/s40168-022-01385-x
• 发表时间: 2022-12-07
• 期刊: Microbiome
• 影响因子: 15.5
• 作者: Tee MZ;Er YX;Easton AV;Yap NJ;Lee IL;Devlin J;Chen Z;Ng KS;Subramanian P;Angelova A;Oyesola O;Sargsian S;Ngui R;Beiting DP;Boey CCM;Chua KH;Cadwell K;Lim YAL;Loke P;Lee SC
• 通讯作者: Lee SC

Immune Response and Microbiota Profiles during Coinfection with Plasmodium vivax and Soil-Transmitted Helminths.

• DOI: 10.1128/mbio.01705-20
• 发表时间: 2020-10-20
• 期刊: mBio
• 影响因子: 6.4
• 作者: Easton AV;Raciny-Aleman M;Liu V;Ruan E;Marier C;Heguy A;Yasnot MF;Rodriguez A;Loke P
• 通讯作者: Loke P

Efficacy of triple dose albendazole treatment for soil-transmitted helminth infections.

• DOI: 10.1371/journal.pone.0272821
• 发表时间: 2022
• 期刊: PloS one
• 影响因子: 3.7

Genetic and Environmental interactions contribute to immune variation in rewilded mice.

遗传和环境的相互作用导致野化小鼠的免疫变异。

• DOI: 10.1101/2023.03.17.533121
• 发表时间: 2023
• 期刊: bioRxiv : the preprint server for biology
• 作者: Oyesola,Oyebola;Downie,AlexanderE;Howard,Nina;Barre,RamyaS;Kiwanuka,Kasalina;Zaldana,Kimberly;Chen,Ying-Han;Menezes,Arthur;Lee,SooChing;Devlin,Joseph;Mondragón-Palomino,Octavio;Souza,CamilaOliveiraSilva;Herrmann,Christin;Kor
• 通讯作者: Kor