Roles of Archaea in infectious disease

项目总结 人类胃肠道(GI)含有数以万亿计的微生物，统称为 微生物区系。居留的微生物群在人类健康中扮演着复杂的角色。例如，微生物群可以 有效地与入侵的病原体竞争营养，从而起到限制或防止 感染。相反，微生物群的某些成员可能会通过产生 促进生长和/或影响毒力基因表达的代谢物。因为两者之间的相互作用 细菌病原体和微生物区系，操纵微生物区系可能是一种创新的治疗手段 传染病。然而，对不同成员的特定角色的更完整的理解是 必填项。到目前为止，大多数研究都集中在属于领域细菌的微生物上，包括 胃肠道中的大多数微生物。值得注意的是，微生物区系也由属于 古生代领域。在古生界中，产甲烷的产甲烷菌是主要成员。 产甲烷菌存在于近100%的世界人口的胃肠道中，并已被提议 对人类健康和/或疾病起着重要作用。尽管如此， 产甲烷菌对人类健康的影响几乎是未知的。因此，特定目标1将评估如何抑制 体内的产甲烷活性通过入侵的细菌病原体影响疾病的进展。具体目标2 将使用定义的微生物区系调查产甲烷菌对肠道感染的影响。

PROJECT SUMMARY The human gastrointestinal (GI) tract harbors trillions of microbes that are collectively referred to as the microbiota. The resident microbiota play complex roles in human health. For example, the microbiota may effectively compete for nutrients against invading pathogens and thereby act as a barrier to limit or prevent infections. Conversely, certain members of the microbiota may enhance pathogen infection by producing metabolites that enhance growth and/or influence virulence gene expression. Because of the interplay between bacterial pathogens and the microbiota, manipulation of the microbiota may be an innovative means to treat infectious diseases. However, a more complete understanding of the specific roles of distinct members is required. To date, most studies have focused on microbes belonging to the domain Bacteria, which comprise the majority of microbes in the GI tract. Significantly, the microbiota is also comprised of microbes belonging to the domain Archaea. Of the Archaea, the methane-producing methanogens are the predominant members. Methanogens are present in the GI tract of nearly 100% of the world’s population and have been proposed to play an important role in human health and/or disease. Despite this fact, the functional contributions of methanogens to human health are virtually unexplored. Accordingly, Specific Aim 1 will assess how inhibiting methanogenic activity in vivo influences disease progression by an invading bacterial pathogen. Specific Aim 2 will investigate the impact of methanogens on enteric infection using a defined microbiota.