Archaea were only classified as a separate kingdom in the late 20th century. Archaea are associated with the ancient origins of life on earth and were assumed to inhabit only extreme environments like hydrothermal vents and salt lakes. However, the surprising discovery that Archaea are widespread and include mesophiles has led to the question of what role these organisms might play in human health and disease. In contrast to hundreds of bacterial species, only a few archaeal species have been identified in humans. These are predominantly the methanogens found in the oral cavity and the gastrointestinal tract. In addition, an extreme halophile in colonic tissue and a thermoacidophile in subgingival plaque have been detected. Although these organisms appear to have less stringent growth requirements than many extremophiles, they may inhabit extreme microniches that could exist within the human body. In addition to these Archaea that are members of the phylum Euryarchaeota, faecal samples were found to contain phyla of the Crenarchaeota, whose divergence from Euryarchaeota is far greater than phyla within bacteria or Eukarya. Many of these were identified as Sulfolobales, of which the only cultured examples are thermoacidophiles. How these organisms have adapted to their human environments remains unknown. This review presents the diversity of Archaea identified in human samples, as well as factors limiting their detection. The known associations of Archaea with disease that may indicate a possible cause will be explored. Finally, a comparison will be made with known pathogens to address the possibility that Archaea could evolve virulence and cause disease.
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