Archaea in and on the Human Body: Health Implications and Future Directions

June Archaea in and on the Human Body: Health Implications and Future Directions Mor N. Lurie-Weinberger 0 1 Uri Gophna 0 1 0 Editor: Joseph Heitman, Duke University Medical Center , UNITED STATES 1 Department of Molecular Microbiology and Biotechnology, George S. Wise Faculty of Life Sciences, Tel Aviv University , Tel Aviv , Israel Although they are abundant and even dominant members of animal microbiomes (microbiotas), from sponges and termites to mice and cattle, archaea in our own microbiomes have received much less attention than their bacterial counterparts. The fact that human-associated archaea have been relatively little-studied may be at least partially attributed to the lack of any established archaeal human pathogens [1,2]. Clinically oriented microbiology courses often do not mention archaea at all, and most medical school and biology students are only aware of archaea as exotic extremophiles that have strange and eukaryotic-like molecular machinery. Since archaea have been known to be associated with the human gut for several decades, one would think that human microbiome studies may unravel new facets of archaea-human interactions. However, adequate universal primers that amplify both bacterial and archaeal small 16S rRNA genes but not any host rRNA genes were only published in mid-2011 [3], and thus, many studies chose to focus on bacteria alone rather than multiply effort and expense to cover taxa that are considered secondary in importance, if not altogether rare. Here, we provide a brief overview of what is currently known about archaea in and on the human body and their potential effects on human health (for additional reviews on archaea and their potential involvement in human disease, see [4-8]). - OPEN ACCESS Competing Interests: The authors have declared that no competing interests exist. The human large intestine (colon), in healthy individuals, has extremely low oxygen concentrations, and over 90% of its microbiota are strict anaerobes. Researchers taking metagenomic fecal microbiota surveys of adult Europeans could assign about 0.8% of the genes in their dataset to archaea [ 9 ], and similar numbers (0.2%–0.3%) were reported for Amerindians and Malwaians [ 10 ], while North Americans had much lower fractions (<0.05%). With the exception of a single report indicating the presence of halophilic archaea in biopsies of inflammatory bowel disease patients [ 11 ], archaea that reside in the human colon are nearly always methanogens. Most of these strict anaerobes belong to the order Methanobacteriales (Fig 1), the most common genera being the closely related Methaonbrevibacter and Methanosphaera. Methanobrevibacter (previously called Methanobacterium) was first isolated from human stool as early as 1968 [ 12 ], followed nearly 15 years later by the discovery that such fecal isolates belonged to the species Methanobrevibacter smithii. M. smithii has been shown to be present in up to 95.7% of human subjects [ 13 ], and to be the most abundant methanogen in the human gut by several studies, comprising up to as much as 10% of all anaerobes found in a healthy individual's colon [ 14–16 ]. Remarkably, its abundance appears to remain stable over time, even following radical dietary changes [ 17 ], and it is highly heritable, meaning that monozygotic twins are more concordant for its presence, or absence, than dizygotic twins [ 18,19 ]. Importantly, substrates for Fig 1. The distribution of human-associated archaea in the phylogenetic tree of the domain Archaea. Tree is based on [63], and [ 64 ]. Highlighted are groups that contain human-associated members. methanogenesis, such as H2, methanol and acetate, are mostly derived from the end products of bacterial fermentation. The second most abundant methanogen in this environment is Methanosphaera stadtmanae. This organism, which has the most restricted energy metabolism of all known methanogenic archaea, is totally dependent on acetate as a carbon source, and its methane production requires methanol and hydrogen [ 20 ]. The human colon and other mammalian intestines are dominated by hundreds of bacterial species [ 14 ], and it is therefore not 2 / 8 surprising to observe that the genomes of M. smithii and M. stadtmanae appear to be very rich in inter-domain lateral gene transfers, especially relating to glycosyltransferases and ABC transporters in both species and adhesin-like proteins in M. smithii [ 21,22 ]. These laterally acquired genes are thought to have played a significant role in these organisms' initial adaptation to mammalian hosts [ 21,22 ]. Both of these species have been recently shown to induce monocyte-derived dendritic cell maturation, and M. stadtmanae also induced a strong pro-inflammatory cytokine release from these cells [ 23 ] and is more prevalent in patients with inflammatory bowel disease [ 24 ]. In ruminants, presence of the methanogen Methanobrevibacter ruminantium can result in lo (...truncated)