Archaea represent a separate domain of life, next to bacteria and eukarya. As components of the human microbiome, archaea have been associated with various diseases, including periodontitis, endodontic infections, small intestinal bacterial overgrowth, and urogenital tract infections. Archaea are generally considered nonpathogenic; the reasons are speculative because of limited knowledge and gene annotation challenges. Nevertheless, archaeal syntrophic principles that shape global microbial networks aid both archaea and potentially pathogenic bacteria. Evaluating archaea interactions remains challenging, requiring clinical studies on inflammatory potential and the effects of archaeal metabolism. Establishing a culture collection is crucial for investigating archaea functions within the human microbiome, which could improve health outcomes in infectious diseases. We summarize potential reasons for archaeal nonpathogenicity, assess the association with infectious diseases in humans, and discuss the necessary experimental steps to enable mechanistic studies involving archaea.

古细菌代表着一个独立的生命领域，仅次于细菌和真核生物。作为人类微生物群的组成部分，古细菌与多种疾病有关，包括牙周炎、牙髓感染、小肠细菌过度生长和泌尿生殖道感染。古细菌通常被认为是非致病性的；由于知识有限和基因注释的挑战，其原因是推测性的。然而，塑造全球微生物网络的古细菌互养原理对古细菌和潜在的致病细菌都有帮助。评估古菌相互作用仍然具有挑战性，需要对炎症潜力和古菌代谢影响进行临床研究。建立培养物保藏中心对于研究人类微生物组内古细菌的功能至关重要，这可以改善传染病的健康结果。我们总结了古细菌非致病性的潜在原因，评估了与人类传染病的关联，并讨论了必要的实验步骤，以实现涉及古细菌的机制研究。