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

基本信息

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
项目类别：
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

项目摘要

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，蠕虫感染会影响人体免疫反应，但我们不完全了解蠕虫的影响可能是间接的。通过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作用。强大的全身免疫调节作用。微生物群可能是导致“卫生假说”和不断上升的环境因素发达国家自身免疫性疾病的发病率是菌群失调（微生物群落失调）。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。我们研究了蠕虫定植对马来西亚土著微生物群的影响，称为“ “原住民”。我们的初步结果已确定微生物之间存在拮抗关系。以拟杆菌目或梭菌目为主的群落梭菌目的扩张。拟杆菌属群落可以由 2 型细胞因子（IL-4 和 IL-13）驱动，从而促进增加杯状细胞产生的粘液可以直接促进人类梭菌菌株的生长。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拟杆菌即使没有蠕虫感染，也是占主导地位的社区。蠕虫定植的梭状芽胞杆菌群落促进宿主体内的抗炎反应；来自原住民的梭状芽胞杆菌菌株在免疫调节方面比现有菌株更有效。饮食和营养摄入的影响以及蠕虫定植与细菌之间的相互作用为了检验这些想法，我们将评估红毛猩猩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群与饮食调查一起，拟议的领域。研究将对蠕虫定植个体进行纵向分析，以确定因果关系最后，我们将从原住民中分离出菌株。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、微生物群和感染等交叉点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我们的研究建立在洛克博士（纽约大学）和林博士（纽约大学）之间的现有合作基础上。马来亚）、Cadwell 博士（纽约大学）和 Bonneau 博士（纽约大学）在寄生虫学、微生物群研究方面拥有专业知识，微生物学和免疫学、流行病学和现场研究、计算生物学和生物统计学。上述目标的实现将对生活在发展中国家和发展中国家的个人产生重要影响。国家以及发达国家。

项目成果

期刊论文数量（14）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genetic and epigenetic coordination of cortical interneuron development.

皮质中间神经元发育的遗传和表观遗传协调。

DOI：
发表时间：
2021
期刊：
影响因子：
64.8
作者：
Allaway, Kathryn C;Gabitto, Mariano I;Wapinski, Orly;Saldi, Giuseppe;Wang, Chen;Bandler, Rachel C;Wu, Sherry Jingjing;Bonneau, Richard;Fishell, Gord
通讯作者：
Fishell, Gord

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

感染蠕虫的马来西亚土著人的肠道微生物组取决于具体情况。

DOI：
发表时间：
2022-12-07
期刊：
影响因子：
15.5
作者：
Tee, Mian Zi;Er, Yi Xian;Easton, Alice V;Yap, Nan Jiun;Lee, Ii Li;Devlin, Joseph;Chen, Ze;Ng, Kee Seong;Subramanian, Poorani;Angelova, Angelina;Oyesola, Oyebola;Sargsian, Shushan;Ngui, Romano;Beiting, Daniel P;Boey, Christopher Chiong Meng
通讯作者：
Boey, Christopher Chiong Meng

Apolipoprotein A-I mimetics mitigate intestinal inflammation in a COX 2-dependent inflammatory disease model

载脂蛋白 A-I 模拟物可减轻 COX 2 依赖性炎症疾病模型中的肠道炎症

DOI：
10.21873/anticanres.11238
发表时间：
2024-09-13
期刊：
Anticancer research
影响因子：
2
作者：
D. Meriwether;Dawoud Sulaiman;C. Volpe;Anna Dorfman;V. Grijalva;Nasrin Dorreh;R. Solórzano;Jifang Wang;E. O'connor;J. Papesh;M. Larauche;H. Trost;M. Palgunachari;G. Anantharamaiah;H. Herschman;Martín G. Martín;A. Fogelman;S. Reddy
通讯作者：
S. Reddy

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

间日疟原虫和土源性蠕虫共同感染期间的免疫反应和微生物群特征。

DOI：
发表时间：
2020
期刊：
影响因子：
6.4
作者：
Easton, Alice V;Raciny;Liu, Victor;Ruan, Erica;Marier, Christian;Heguy, Adriana;Yasnot, Maria Fernanda;Rodriguez, Ana;Loke, P'ng
通讯作者：
Loke, P'ng

Viewing the US presidential electoral map through the lens of public health.

从公共卫生的角度看美国总统选举地图。