Symbiotic Interactions of Archaea in Animal and Human Microbiomes

Since the introduction of Archaea as a new domain of life more than 45 years ago, progress in their phylogenetic classification and knowledge of their exclusive biological characteristics has identified archaea as unique microorganisms which are widespread in extreme but also in various moderate ecosystems, including eukaryotic hosts. However, archaea are still neglected players within microbiomes, and research on archaea-bacteria interactions is still in its infancy due to methodological challenges. This review summarizes the current knowledge of archaea as components within microbiomes and focuses on their interactions with their bacterial neighbors and the principles of archaeal interactions. Archaea are common constituents of animal and human microbiomes, which are dominated by Euryarchaeota. The gastrointestinal tract is the most studied body site, where archaea account for up to 4% of all microorganisms, primarily represented by methanogens. No archaeal pathogen has yet been identified, although methanogens are hypothesized to be indirectly involved in pathogenicity. Archaeal interactions comprise symbiotic relationships, and the cell membrane and wall might be as crucial as quorum sensing/quenching for these interactions. Particularly, syntrophic interactions under energy-deficiency stress seem to be an essential strategy for archaea. However, more research is urgently needed to discover how archaea sense their environment, compete with bacteria, and interact within complex microbiomes associated with multicellular organisms.


Introduction
Archaea are prokaryotes belonging to the third domain of life, first classified separately from bacteria in 1977 by Carl Woese and George E. Fox based on their ribosomal RNA genes [1••, 2].Although the classification of archaea is a rapidly progressing field, current classifications categorize this domain into four large clades, namely the Euryarchaeota, the TACK superphylum (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota), the Asgard archaea, and the DPANN clade (Diapherotrites, Parvarchaeota, Aenigmarchaeota, Nanoarchaeota) [3, 4] (Fig. 1).Euryarchaeota represents the most extensively studied phylum as it includes the methanogens, which play an essential role in (syntrophic) anaerobic degradation processes [5] (Fig. 1).
Besides this complex phylogeny, archaea harbor characteristics distinct from the other domains of life [6].These unique characteristics are the lack of peptidoglycans in their cell wall and ether-linked lipids in their cell membrane.Archaea also show higher diversity in cell wall structures, e.g., surface layer proteins and heteroglycans [6].Comparative analyses of archaeal genomes have identified several molecular conserved signatures uniquely present in archaea (l groups).One unique feature of archaea is the metabolic production of methane (methanogenesis) [6].During the last decades, these exclusive properties were mainly regarded as unique adaptions to various extreme environments inhabited by archaea [7].However, several studies have since discovered that archaea also live in moderate habitats, including soil and ocean [8].They have been reported to be stable commensals of multicellular host organisms (plants and animals), where they participate in functions such as growth promotion, nutrient supply, protection against abiotic stress, methanogenesis, transformation of heavy metals, trimethylamine metabolism, and immune modulation (reviewed in [5]).Studies have confirmed the presence of archaea in various human body sites, such as the gut, skin, nose, mouth, lungs, and vagina [9][10][11].Although enormous progress has already been made in archaeal research [12•], their unique physiological, structural, and molecular properties complicate further investigations, particularly in the context of microbiome research [13•, 14••].This review aims to summarize the current knowledge about archaea as components within microbiomes and focuses on their interactions with their bacterial neighbors and the archaeal communication types used for these interactions.

Archaeal Interactions in Natural Ecosystems
Researchers only recently became aware of how archaea interact with each other and organisms of other domains.For instance, methanogens are involved in essential steps of the global methane cycle, partially conducted in a symbiotic interaction with herbivorous animals or sulfatereducing bacteria [15].Many syntrophic associations have been described for hydrogenotrophic methanogens, such as fermentative Acetobacterium and Syntrophobacter, Desulfovibrio, Thermoanaerobacter, Desulfotomaculum, and Pelotomaculum (reviewed in [15]).Besides microbial assemblages, archaea further interact with multicellular eukaryotes.Recent next-generation sequencing studies revealed highly abundant and diverse archaeal signatures in plant-associated microbiomes [16].Particularly, plant roots and rhizospheres provide anoxic or oxygen-depleted microniches for methanogens and ammonium-oxidizing archaea [17].Notably, plant genotypes affected the composition and structure of these archaeal communities [18].The interaction could be based on syntrophic nitrogen cycling, and archaea are suggested to affect the nutrient exchange and coping with environmental stress [19].Although there is initial evidence of specific interactions among archaea and between archaea and other domains of life, their mechanisms and ecological roles often remain unclear.

Archaea in Animals
Animals have been shown to be inhabited not only by trillions of bacteria and fungi but also by archaea, more precisely primarily Euryarchaeota, with a high abundance of anaerobically growing methanogens found within their digestive tracts [7].Only a few studies have reported Crenarchaeota and Thaumarchaeota within animal microbiomes [20,21].The presence of archaea has been confirmed in sponges, mollusks, corals, arthropods, vertebrates, and humans (reviewed in [5,15]).Investigations using Axinella sponge species associations with Cenarchaeum symbiosum or other filamentous Crenarchaeota [22], and the symbiosis of the demosponge Tentorium semisuberites with Cren-and Euryarchaeota [23], pointed to an archaeal contribution to the sponge nitrogen metabolism.A role within nitrogen cycling has also been identified in marine mollusks for Thaumarchaeota phylogenetically related to Nitrosopumilus maritimus [24].Among arthropods, the largest animal phylum, exclusively methane-producing archaea were detected in millipedes, cockroaches, termites, and scarab beetles [25].Here, the methanogens were primarily found in the hindguts of these animals [26].In these interactions, archaea utilize hydrogen, carbon dioxide, and acetate resulting from the anaerobic degradation of lignocellulose [27].
Within the methanogenic archaea, particularly Methanobrevibacter species are extraordinarily well-adapted to interact with animal hosts and microbial neighbors [28••].Consequently, Methanobrevibacter species are the predominant archaea in the gastrointestinal tracts (GITs) of various ruminants and non-ruminants, including cattle, sheep, reindeer, goats, buffalo, pigs, rhinoceroses, and chickens, among others (reviewed in [5, 28••]).In ruminants, archaeabacteria consortia produce more than one-third of the methane [29].Systematic analyses of methane production in the guts of over 250 vertebrates revealed that methane production and, thus, the presence of methanogens depends on the phylogenetic lineage [25].Methanobrevibacter were shown to be flexible exponents of syntrophic interactions that enhance the efficiency of bacterial polysaccharide fermentation through methanogenesis since they can consume various fermentation products of primary and secondary fermenters, such as methanol, hydrogen, and carbon dioxide [30].Methanobrevibacter smithii is known as a partner in a syntrophic interaction with Bacteroides thetaiotaomicron [31].Here, the archaeon affected the expression of Bacteroides enzymes responsible for producing formate and acetate, which the archaeon utilizes.In gnotobiotic mice, the consortium was assumed to affect the energy balance of the host [32].Furthermore, other methanogenic archaea, like Methanosphaera, Methanosarcina, Methanomassiliicoccus, and Methanimicrococcus, have been identified in the gut of various animals despite their low abundance [5].Besides the archaeal colonization of the GIT, various animals also carry methanogens, Haloarchaea and Thaumarchaeota on the skin [33].Also, those archaeal groups consume metabolic end products from the host and the microbiome and are supposed to affect the host [34 ••].Although the archaeal community, also called archaeome, is now increasingly recognized as an essential component of (host-associated) microbiomes, contributing to methane production and potentially involved in disease-relevant processes, the underlying interaction mechanisms are still largely unknown [28••].

Role of Archaea in Humans
The human microbiome contains numerous archaea, particularly on the skin, in the respiratory tract, and in the GIT [10] (Fig. 2).Several studies estimated that approx.500-1000 different microbial species are present within the human body at any time, accounting for 4 × 10 13 cells.Archaea are predicted to account for around 1% of the total microbial cell count [35].The human archeaome includes many lineages, including Methanobacteriales, Methanomassiliicoccales, Methanomicrobiales, Methanosarcinales, Halobacteriales, Thaumarchaeota (Nitrososphaeria), and members of the DPANN clade [28••](Fig. 1, 2).The oral cavity harbors various methanogenic strains of the genera Methanobrevibacter and Methanomassiliicoccus, often enriched in patients with periodontal disease [36].Recent studies even identified halophilic and thermophilic Euryarchaeota and Thaumarchaeota in the human mouth [37] (Figs. 1, 2).The human skin is inhabited by Thaumarchaeota (Nitrososphaera), assumed to be responsible for ammonium turnover, and associated with odor reduction and skin improvement [33] (Fig. 2).Further, age and skin physiology affect the human skin archaeome [38].Few studies describe the presence of archaea in human nasal, lung, and vaginal microbiomes [39••] (Fig. 2).As mentioned for animals, the vast majority of human-associated archaea is found in the intestine, accounting for up to 10% of the anaerobic community [40] (Fig. 2).The abundance of methanogenic archaea in the human gut is highly variable and represented by two physiological types of humans regarding gas exhalation (methane emitters and non-emitters) [41•].While the specific role of non-methanogenic archaea in the human body remains to be explored, methanogens maintain numerous syntrophic relationships with resident bacteria by being involved in fermentation processes through hydrogen removal [28••].M. smithii was the first archaeon isolated from human feces and is the most abundant archaeon found in the intestine [42].M. smithii genomes displayed genomic adaptations to the human gut, such as producing surface glycans and adhesion-like proteins [30].These adaptations are considered to originate from bacteria through lateral gene transfer [43].Besides M. smithii, other methanogens such as Methanosphaera stadtmanae, and Methanomassiliicoccus luminyensis have been detected in human stool samples [44].The use of modern high-throughput sequencing techniques revealed the presence of additional community members from the Eury-and Crenarchaeota, such as Desulfurococcales, Crenarchaeales, Sulfolobales, Thermoproteales, Archaeoglobales, Halobacteriales, Methanosarcinales, Methanobacteriales, Methanococcales, Methanopyrales, Thermococcales and Thermoplasmatales within the human intestine [45].
Although archaea can generally be considered commensal or beneficial organisms, and no archaeal pathogen is currently known, reports of archaeal involvement in human diseases are accumulating, particularly in immunocompromised individuals [46••].Archaea have been found to have immunomodulatory abilities.For example, certain species of archaea can stimulate the immune system, increasing the production of cytokines and other immune cells [28••, 42, 47].Other studies have suggested that archaea can exert anti-inflammatory effects by reducing the production of proinflammatory cytokines, such as methanogenic archaea, or increasing the production of anti-inflammatory cytokines [42,48] stadtmanae was more abundant in the gut microbiome of patients with inflammatory bowel disease (IBD) [52] and may be associated with an increased risk of other autoimmune diseases, such as type 1 diabetes [53].However, the effects of these interactions are not yet fully understood, and more research is needed to determine the precise ways archaea may affect the human immune system.It is also possible that different species of archaea may have different effects on the immune system and that the effects may depend on the context in which the interaction occurs.
Increasing evidence suggests that archaea may play a role in the development and progression of cancer in humans through various mechanisms, including the production of carcinogenic metabolites, modulation of immune responses, and alteration of the tumor microenvironment [54,55].Further, alterations in the abundance and diversity of archaeal populations may be associated with an increased risk of colorectal cancer [55].For example, certain species of archaea, such as M. smithii, may be more abundant in the gut microbiome of individuals with colorectal cancer than in healthy individuals [56].Similarly, hydrogen sulfide-producing archaea have been implicated in the development of gastric cancer due to the ability of hydrogen sulfide to cause DNA damage and inhibit apoptosis [57].Other studies have suggested that archaea may be involved in oral infections and periodontitis [36,58].In particular, Methanobrevibacter oralis has been identified in the oral microbiomes of patients with periodontitis [59].

Principles of Archaea-Bacteria Interactions -Examples
Several types of symbiosis are known for microorganisms, including mutualism, commensalism, amensalism, parasitism, and predation [60].These different types of symbiosis can have significant implications for microbial communities' ecology and function and host organisms' health and wellbeing.An example of a mutualistic relationship involving archaea, also called syntrophy, is the previously mentioned interaction between methanogenic archaea and anaerobic bacteria in the gut of ruminants [61] (Fig. 3, mutualism).Ruminants, such as cows, have a complex digestive system that allows them to break down rigid plant materials through fermentation.Methanogenic archaea are an essential part of this process, as they produce methane as a byproduct of the fermentation process.However, methane production is energetically costly, and the methanogens rely on other microbes in the gut to provide them with the necessary substrates for methane production.In exchange for these substrates, the methanogens provide the other microbes with an environment free of hydrogen gas, which is toxic [61,62].Moreover, the archaeon Acidianus and the bacterium Desulfurococcus coexist in acidic hot springs to perform sulfur cycling [63].Acidianus oxidizes elemental sulfur to sulfuric acid, while Desulfurococcus reduces sulfate to sulfide.The interaction between these two microorganisms benefits both, as Acidianus provides Desulfurococcus with the sulfuric acid it needs to produce energy, and in turn, Desulfurococcus consumes the toxic sulfide produced by Acidianus.Within nitrogen cycling, the ammonia-oxidizing archaeon N. maritimus and the nitrite-oxidizing bacterium Nitrospira coexist in marine environments [64].N. maritimus provides Nitrospira with the nitrite it needs to produce energy, and in turn, Nitrospira consumes the toxic nitrite produced by N. maritimus.Commensal symbiosis including archaea was shown in the guts of termites and humans, where one organism benefits from the association while the other is neither benefited nor harmed [65].Similarly, methanogens at the surface of corals detoxify the environment [66](Fig.3, commensalism), and in the soil, they degrade complex organic matter used by other microbes [67].Amensalism describes a relationship with one partner negatively impacted by the presence of another organism while this organism is unaffected at all.One example of amensalism involving archaea can be again found in human guts [68].M. smithii produces methane as a byproduct of its metabolism, while Desulfovibrio piger produces hydrogen sulfide as a byproduct.The presence of D. piger in the gut can reduce the sulfate levels available for M. smithii, thus inhibiting the growth and activity of the archaeon [30,69] (Fig. 3, amensalism).Sulfur compounds are also essential for the survival of archaea and bacteria in deep-sea hydrothermal vents; consequently, the organisms compete with each other and get both negatively impacted [70].For instance, Thermococcus can outcompete sulfur-reducing bacteria for sulfur compounds, using specialized enzymes that enable them to oxidize sulfur compounds to sulfate, releasing energy in the process [71] (Fig. 3, competition).Other archaea, such as Methanosarcina, can also outcompete sulfur-reducing bacteria by consuming hydrogen and carbon dioxide, which can limit the availability of these compounds for bacterial growth [72].Archaea, like Methanosaeta harundinacea and Haloferax volcanii, compete with other microorganisms for space in their environment by forming biofilms and thus preventing the colonization of others [73].There are currently no verified examples of archaea that are obligate parasites of other organisms.However, some archaea interact with other organisms in a way that can be considered to be parasitic [74].For instance, some archaeal species have been found to live as endosymbionts in protists or amoebae [44].M. luminyensis has been found in the ciliate protozoan Trimyema compressum [75], M. arboriphilicus in the amoeba Acanthamoeba polyphaga [76], and M. stadtmanae in the ciliate protozoan Metopus contortus [77].A parasitic relationship exists between the thermoacidophilic archaeon Sulfolobus and the double-stranded DNA virus Sulfolobus Turreted Icosahedral Virus (STIV) [78] (Fig. 3, parasitism).STIV is an obligate parasite of Sulfolobus and depends on its host for replication and survival.STIV uses the host's cellular machinery upon infection to replicate its genome, assemble new virus particles, and lyse the host cell to release the new virus particles [79].The virus has evolved various mechanisms to manipulate the host's cellular processes for its benefit [80].For example, it encodes several proteins that can disrupt the host's DNA repair mechanisms, thus preventing the host from repairing the DNA damage caused by the virus.STIV also encodes proteins that suppress the host's immune response, allowing the virus to evade detection and destruction by the host's defense mechanisms [80].Archaea are generally not considered predators, lacking the specialized structures and mechanisms to capture and consume other microorganisms.However, predation of archaea Fig. 3 Archaeal interactions.Interactions can be beneficial, neutral, or harmful for one or both partners and can take many forms, including mutualism (methanogenic archaea and anaerobic bacteria both benefit in the gut of ruminants), commensalism (methanogens at the surface of corals detoxify the environment), amensalism (Desulfovibrio piger reduces sulfate levels unavailable for Methanobrevibacter smithii), predation (Parcubacteria feed on archaea in soil ecosystems), parasitism (Sulfolobus Turreted Icosahedral Virus (STIV) is an obligate parasite of Sulfolobus), competition (archaea and bacteria compete for sulfur compounds in deep-sea hydrothermal vents), and neutralism (archaea coexist with other microbes).Created in BioRender.com is assumed to occur [81].For example, Parcubacteria (also known as Candidate Division OD1) from soil ecosystems are known to feed on archaea, and some protists can engulf and digest archaea as a food source [82].The dorvilleid polychaete, Ophryotrocha labronica, completes its life cycle by preying on two strains of Euryarchaeota -Haloferax and Halobacterium.Both archaea offered unique lipids to the polychaete [83](Fig.3, predation).Lastly, archaea simply coexist within complex microbiomes with other microbes without direct consequences for the neighbors and the host [5] (Fig. 3, neutralism).These are just a few examples of the complex interactions between archaea and bacteria in microbiomes.The exact nature and importance of these interactions can vary depending on the specific microbiome and the types of microorganisms present.

Communication of Archaea
Archaea can communicate with each other and other microorganisms in their environment through various mechanisms, including cell-cell contact, chemical signaling, and quorum sensing (QS) [84,85] (Fig. 4).Archaea interact with their environment through their unique cell membranes that are composed of ether-branched chain lipids (isoprenoids), enabling to withstand extreme conditions such as high temperatures, high salinity, and low pH [86] (Fig. 4).Archaea also have unique cell walls that can vary in composition depending on the specific type of archaea.Structures like Pseudomurein, S-layers, sheaths, and Methanochondroitin provide structural support and protection and facilitate communication and exchange of nutrients between cells [87] (Fig. 4).Beyond, archaea have specialized structures to interact with their environment, communicate with other cells, and move in response to changing conditions [88] (Fig. 4), among those the archaellum, a whip-like structure similar to the bacterial flagellum, is used for movement [89].Further, pili and fimbriae, hair-like structures, are involved in adhesion to surfaces and conjugation [88].For instance, Methanococcus voltae has type IV pili that help it to attach to surfaces [90]; Methanocaldococcus jannaschii, produces long, filamentous pili, allowing them to interact with their environment (motility), form complex communities with other microorganisms (adhesion to surfaces and cells), and adapt to changing conditions (conjugation) [91].H. volcanii, Sulfolobus spp., and Thermococcus spp.form pili for conjugation (also known as mating and fusion, respectively) to transfer genetic material between cells through direct contact [92].Nanotubes, which are long, thin structures, connect Ignicoccus hospitalis cells and allow the exchange of cytoplasmic material for metabolic cooperation between cells [93].Other archaea, such as Thermococcus and Pyrococcus, have thread-like structures for attaching to surfaces or for movement [94], while some thermophilic and hyperthermophilic archaea, including members of the Pyrodictium and Ignicoccus, form cannulae.Cannulae are hollow, needle-like structures that connect neighboring cells for exchanging materials and information between them [95].As unique long, flexible, grappling hook-like structure, Nanoarchaeum equitans has hami, used to attach to the surface of Ignicoccus [96].Archaeal species, such as H. volcanii and Sulfolobus acidocaldarius can further produce small membrane vesicles, spherical structures that bud off the cell membrane [97].These vesicles can contain a variety of molecules, including enzymes and signaling molecules facilitating nutrient uptake, communication, and defense against environmental stressors.
Chemical signals, such as (small) molecules or gases, are released by archaea into the environment and detected by other microorganisms in the vicinity, allowing for coordinated responses to changing environmental conditions [84].Some of the most common chemical signals archaea use include metabolites that can influence the growth and behavior of other microorganisms [84].For example, some methanogenic archaea produce acetate, which other microbes in the syntrophic relationship can use [98].Similarly, extracellular enzymes are exchanged in syntrophic interactions [99].Archaea can also use electron shuttles to interact with other microbes.Bacteria provide methanogenic archaea with electron donors, and the archaea provide the bacteria with a stable environment and a sink for the end-products of their metabolism [100].Extracellular polymeric substances (EPS) produced by biofilm-forming archaea are other chemical signals in the attachment of cells to surfaces, each other, and other microbes [101].EPS can play various roles, including cell attachment, nutrient uptake, and protection against environmental stress.Some archaeal species, such as the halophilic archaeon Halobacterium salinarum, produce EPS to survive in high-salt environments [102].Another way archaea communicate is through quorum sensing (QS), a process by which microorganisms can detect the density of other microorganisms in their environment and adjust their behavior accordingly [85] (see Excursion -Quorum sensing in Archaea).Overall, the mechanisms by which archaea communicate in microbiomes are still not well understood, and further research is needed to elucidate the specific signaling pathways and molecules involved.However, communication and cooperation among various microorganisms are critical for the formation and function of microbial communities in their environment [8].

Excursion -Quorum Sensing in Archaea
Archaea use QS for cell-to-cell communication [85].QS is a process by which microorganisms detect the density of their population and regulate gene expression as a community [103].This can be beneficial for microbial survival and growth, as well as for interactions with host organisms and other microbiome members [104].It typically involves producing, releasing, and detecting small signaling molecules called autoinducers.When the concentration of autoinducers in the environment reaches a certain threshold, it triggers a response that can result in changes in gene expression, behavior, or metabolism [103].Overall, the use of QS among archaea is less well studied than in bacteria, but recent research has shed more light on the phenomenon in these organisms [85].Several types of signaling molecules have been identified in archaea, including acyl-homoserine lactones (AHLs) [85].These are signaling molecules commonly used by Gram-negative bacteria [105•].However, AHLs have also been found in some archaea, such as Methanococcus maripaludis [106].Recently, 11 new archaeal isolates with AHL-like activity against the LuxR-based AHL biosensor, including thermophiles, were identified [85,107,108].Multiple AHL-like signal molecules were detected in Haloferax mucosum, Halorubrum kocurii, Natronococcus occultus, and H. salinarium [85].A modification of AHL signaling molecules by a carboxyl group seems unique to archaea [106], and in M. harudinacea carboxyl-AHLs are assumed for one-way inter-domain cross-talk [106].The work on M. harundinacea also described a putative AHL synthase, FilI, a histidine kinase different from any known bacterial AHL synthase [106].Diketopiperazines (DKPs), known as signaling molecules in the bacteria Pseudomonas aeruginosa, Bacillus subtilis, and Streptomyces sp., have also been detected in archaea [109].DKPs were suggested for regulating protease activity in Natronoccocus occultus [109].Autoinducer-2 (AI-2) was shown to be involved in inter-species communication and biofilm formation in some archaea, e.g., Methanosarcina acetivorans, M. maripaludis, and Sulfolobus solfataricus [110 •].Recent research suggests that QS is crucial in many ecological and physiological processes.The direct evidence for QS in archaea is rare, but many phenotypes commonly regulated by QS in bacteria, such as biofilm formation, extracellular enzyme production, and membrane vesicle formation, are also present in archaea, suggesting a similar QS regulation of those phenotypes in archaea (reviewed in [85]).For instance, a biofilm phenotype associated with AHL activity was described for H. lacusprofundi [107].M. jannaschii produces a phenotypic response when cultured with the bacterium Thermys maritima, potentially relying on QS molecules [111].Co-cultured T. maritima and Pyrococcus furiosus produce AI-2 [111].Moreover, a potential QS signal was observed in the supernatant from a Natrialba magadii culture involved in extracellular enzyme production [112].
Some evidence suggests that quorum quenching (QQ) may be present in certain archaeal species [85].QQ is the process of interfering with QS in microorganisms, often through enzymes or small molecules [113].In the environment, these QQ systems enable the turnover of QS signals in communities allowing for effective change between phenotypes or offering competitive advantages to some organisms by interference with these systems [114].While QQ has been extensively studied in bacteria, it is less understood in archaea [85].In S. solfataricus and S. acidocaldarius, the phosphotriesterase-like lactonases SsoPox and SacPox were identified, respectively, which inhibit short-chain (C4-HSL) and long-chain (3-oxo-C12-HSL) AHLs produced by the opportunistic pathogen P. aeruginosa PAO1 [115].Further, DKPs synthesized by the haloarchaeon Haloterrigena hispanica might act as AHL mimics, blocking AHL detection of neighboring bacteria [109].Further research is needed to fully understand the prevalence and significance of QS and QQ in archaea.

Conclusion
Recent research has highlighted the importance of communication between archaea and bacteria during microbemicrobe interactions, particularly in the context of symbiotic relationships within animal and human microbiomes.While bacteria have long been recognized as key players in microbiome ecology and function, emerging evidence suggests that archaea also play essential roles in these complex microbial communities.Studies have shown that archaea and bacteria can exchange chemical signals, such as QS molecules, to coordinate their activities and respond to environmental changes.In particular, symbiotic archaea have been found to play important roles in host digestion, metabolism, and immune function, highlighting the importance of understanding archaea-bacteria communication for human health.Overall, the growing recognition of archaea as key players in microbial communities underscores the need for further research into the mechanisms and consequences of archaea-bacteria communication during microbe-microbe interactions.
Funding Open Access funding enabled and organized by Projekt DEAL. 1.

Fig. 1
Fig. 1 Archaeal phylogeny.Schematic representation of a Maximum Likelihood phylogenetic tree based on 16S rRNA sequences from Archaea and Bacteria, adapted from [3] . The exact mechanisms by which archaea exert their immunomodulatory effects are not yet fully understood, but it is thought that they may act through interactions with the gut microbiome and the gut epithelial cells [28 ••].Other studies have proposed that archaea may interact with Tolllike receptors (TLRs) on immune cells, activating immune responses [49].It is assumed that M. smithii may contribute to developing autoimmune diseases through various mechanisms, including producing metabolites, like methane, that activate immune cells and stimulate inflammation [34 ••].In addition to its direct effects on the immune system, M. smithii may also indirectly contribute to autoimmune disease development by altering the gut microbiome and disrupting the balance of commensal microorganisms [50, 51].Dysbiosis has been implicated in the development of various autoimmune diseases (reviewed in [28••]).Furthermore, M.

Fig. 2
Fig. 2 Human archaeome.Archaea identified in different body sites of humans.Created in BioRender.com

Fig. 4
Fig. 4 Archaeal communication.Archaea interact in symbiotic relationships by exchanging genetic material and molecules to coordinate processes like biofilm formation.Various cell membrane structures

The paper provides an overview of the diversity, ecology, and evolution of archaea, highlighting recent advances in genomic and metagenomic techniques. The authors discuss the key fea- tures that distinguish archaea from bacteria and eukary- otes and explores the various ecological niches that archaea occupy. The authors highlight the important roles that archaea play in global nutrient cycling and discusses the evolutionary history of archaea.
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authors review recent advances in our understanding of the archaeal microbiome, focusing on the various host- associated environments where archaea have been identified, including the gut, oral cavity, skin, and genital tract. They discuss the diversity of archaeal taxa that have been identi- fied in these environments, and the potential roles that they may play in host physiology and disease. used metagenomic sequencing to analyze the archaeal diver- sity in fecal samples from over 1,000 individuals from various geographic locations and populations. They identified over 1,100 archaeal genomes, including many previously unknown species, and performed a detailed phylogenetic analysis to classify these genomes into distinct clades. The paper also provides insights into the functional potential of the human gut archaeome, identifying genes and pathways related to various metabolic processes and highlighting the potential roles of archaea in nutrient cycling and other gut functions
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