Investigations of Parasite-Host-Microbiota Interactions Using Cutting-edge Genomics and bioinformatics technologies

利用尖端基因组学和生物信息学技术研究寄生虫-宿主-微生物群相互作用

• 批准号: 1643688
• 金额: --
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1643688
• 关键词: Investigations; Parasite; Host; Microbiota; Interactions

The increased incidence of allergic and autoimmune disorders in developed countries has been attributed to a decline in childhood exposure to pathogens that causes inappropriate immune responses to harmless stimuli. Thus, several attempts have been made to exploit this 'hygiene hypothesis' by reintroducing some of these infectious agents, particularly intestinal worms, into patients as novel immunotherapy. However, the precise mechanisms by which worms modulate the immune system are unclear. Recent studies have established a link between infections by gastrointestinal parasitic helminths and modifications of the composition of the gut microbiota and relative abundance of selected microbial species, thus prompting the hypothesis that the ability of gastrointestinal parasites to modulate the immune response of the vertebrate hosts may be in part associated to changes in the commensal makeup. However, thus far, data on the interactions between parasitic helminths, vertebrate hosts and their commensal microbiota is lacking. Elucidating the complex relationships between the parasite, the host and the gut microbiota is crucial, because of an increasing need for an integrated approach to understand host---pathogen interactions that, in turn, underpin the translation of experimental findings to the clinic. Recent technological advances provide unique opportunities to investigate various aspects of these interactions. For instance, high---throughput sequencing platforms, together with bioinformatics techniques that allow timely processing of large sequence outputs, enable the identification of host genes and microbial populations and/or species associated with the establishment of a parasite in the gastrointestinal tract of its definitive host. The specific research aims of this project will be: (1) to determine helminth---induced changes in gut microbiota following experimental infection of vertebrate hosts; (2) to conduct analyses of transcriptional regulation following parasite infection using next---generation sequencing technologies and bioinformatics; (3) to establish the role of the gut microbiota and the relative contribution of helminth---induced modulation of host gene expression in parasite---mediated suppression of inflammation; (4) to select candidate bacterial species for the development of novel helminth---based therapies of gut inflammatory disorders. This interdisciplinary project will integrate key areas of parasitology, microbiology, immunology, genetics, molecular biology and bioinformatics and will provide essential skills in these areas. This project is timely, since its outcomes will not only have broad implications for future studies of the biology and origin of parasitism itself, but will also pave the way to investigations aimed at exploiting the immunoevasive strategies of parasites for the development of helminth---based therapeutics for chronic inflammatory disorders.

发达国家过敏性和自身免疫性疾病发病率的增加归因于儿童期接触病原体的减少，这些病原体导致对无害刺激的不适当免疫反应。因此，已经进行了几次尝试，以利用这种“卫生假说”，通过重新引入一些这些传染性病原体，特别是肠道蠕虫，到患者作为新的免疫疗法。然而，蠕虫调节免疫系统的确切机制尚不清楚。最近的研究已经建立了胃肠道寄生蠕虫感染与肠道微生物群组成的改变和所选微生物物种的相对丰度之间的联系，从而促使假设胃肠道寄生虫调节脊椎动物宿主免疫反应的能力可能部分与肠道组成的变化有关。然而，到目前为止，寄生蠕虫，脊椎动物宿主和他们的肠道微生物群之间的相互作用的数据是缺乏的。阐明寄生虫，宿主和肠道微生物群之间的复杂关系至关重要，因为越来越需要一种综合方法来了解宿主-病原体相互作用，这反过来又支持将实验结果转化为临床。最近的技术进步提供了独特的机会，调查这些相互作用的各个方面。例如，高通量测序平台，加上生物信息学技术，允许及时处理大序列输出，使宿主基因和微生物种群和/或物种的鉴定与建立一个寄生虫在其最终宿主的胃肠道。本项目的具体研究目标是：（1）确定寄生虫感染脊椎动物宿主后肠道微生物群的变化;（2）利用新一代测序技术和生物信息学分析寄生虫感染后的转录调控;（3）确定肠道微生物群的作用和蠕虫诱导的宿主基因表达调节在寄生虫介导的炎症抑制中的相对贡献;（4）筛选候选菌种，用于开发新的以蠕虫为基础的肠道炎症性疾病的疗法。这一跨学科项目将整合寄生虫学、微生物学、免疫学、遗传学、分子生物学和生物信息学的关键领域，并将提供这些领域的基本技能。这个项目是及时的，因为它的结果不仅将对未来的生物学和寄生虫本身的起源的研究产生广泛的影响，但也将铺平道路，旨在利用寄生虫的免疫逃避策略的发展蠕虫-为基础的治疗慢性炎症性疾病的调查。

项目成果

Helminth infections and gut microbiota - a feline perspective

蠕虫感染和肠道微生物群——猫科动物的观点

• DOI: 10.17863/cam.7732
• 发表时间: 2016
• 作者: Duarte A

The relationships between faecal egg counts and gut microbial composition in UK Thoroughbreds infected by cyathostomins

感染 Cyathostomins 的英国纯种马粪便卵数与肠道微生物组成之间的关系

• DOI: 10.17863/cam.18874
• 发表时间: 2018
• 作者: Cantacessi C

Helminth infections and gut microbiota - a feline perspective.

蠕虫感染和肠道微生物群 - 猫的视角。

• DOI: 10.1186/s13071-016-1908-4
• 发表时间: 2016-12-03
• 期刊: Parasites & vectors
• 影响因子: 3.2
• 作者: Duarte AM;Jenkins TP;Latrofa MS;Giannelli A;Papadopoulos E;de Carvalho LM;Nolan MJ;Otranto D;Cantacessi C
• 通讯作者: Cantacessi C

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease.

• DOI: 10.1038/srep36797
• 发表时间: 2016-11-09
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Giacomin P;Zakrzewski M;Jenkins TP;Su X;Al-Hallaf R;Croese J;de Vries S;Grant A;Mitreva M;Loukas A;Krause L;Cantacessi C
• 通讯作者: Cantacessi C

Changes in duodenal tissue-associated microbiota following hookworm infection and consecutive gluten challenges in humans with coeliac disease

患有乳糜泻的人在钩虫感染和连续麸质挑战后十二指肠组织相关微生物群的变化

• DOI: 10.17863/cam.7124
• 发表时间: 2016
• 作者: Giacomin P