Roles of Archaea in infectious disease

项目摘要 人类胃肠道（GI）含有数万亿微生物，这些微生物被统称为微生物。 微生物群居民微生物群在人类健康中发挥着复杂的作用。例如，微生物群可以 有效地与入侵的病原体竞争营养物，从而作为限制或防止 感染.相反，微生物群的某些成员可以通过产生细菌来增强病原体感染。 增强生长和/或影响毒力基因表达的代谢物。因为这两个因素之间的相互作用 细菌病原体和微生物群，微生物群的操纵可能是一种创新的治疗手段， 传染病然而，对不同成员的具体作用的更完整的理解是 必需的.迄今为止，大多数研究集中在属于细菌域的微生物上，其包括 胃肠道中的大多数微生物。值得注意的是，微生物群也由属于以下的微生物组成： 域的名称。产甲烷菌是产甲烷菌的优势类群。 产甲烷菌存在于几乎100%的世界人口的胃肠道中，并且已被提议用于 在人类健康和/或疾病中发挥重要作用。尽管如此， 产甲烷菌对人类健康的影响实际上是未被探索的。因此，具体目标1将评估如何抑制 体内产甲烷活性通过入侵的细菌病原体影响疾病进展。具体目标2 将使用确定的微生物群研究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.