Great Answer. Thanks Arne!!

Bearing in mind how recently the Archea have been discovered, how do we know they do not cause disease? On the BBC news this morning I hear that rats did not cause the Black Death, also I do not think cholera is a waterborne disease, so perhaps we know far less about infectious diseases than we think?

Thanks Anthony and Enrico for you suggestions. When I imagine precambrian earth, I envisage bubbling pools and lots of volcanic activity, and that the most recent common ancestor of all archea and eukarya thrived in the warmer pools, whilst proto-bacterial species thrived in the cooler pools. I think Arne is right that the virulence/pathogenicity relationships we see now, are driven more by contemporary proximity between species. Many infectious parasites and viral pathogens reside in the animals that we hunt or herd. Many of the bacteria that can make us sick, are also harmless (symbiotic?) comensals as well. It is proximity that facilitates the evolution of virulence/pathogenicity.

Several consideration:

1) I agree with Enrico!

2) Just 12 years ago nitrifying Archaea were discovered.

3) Many Archaea have quite specialised metabolisms. That might still possible that we do not have quite genomes analysis of various Archaea.

I am still a bachelor degree student, but I am currently working on this topic with and from what I know, there are several cases where we are currently discussing the role of Archaea as a pathogen.

Fore more information ,you should check the previous discussion on this topic here. (https://www.researchgate.net/post/Why_are_there_few_or_no_archaeal_pathogens_of_humans?_iepl%5BgeneralViewId%5D=HopdrFCw3nYADOZHY0NeBxhQ01J0H6mw1bkK&_iepl%5Bcontexts%5D%5B0%5D=searchReact&_iepl%5BviewId%5D=XeNV7XnyVALEapf5Qj6IC1vUVt6uinS1OJ1u&_iepl%5BsearchType%5D=question&_iepl%5Bdata%5D%5BcountLessEqual20%5D=1&_iepl%5Bdata%5D%5BinteractedWithPosition1%5D=1&_iepl%5Bposition%5D=1&_iepl%5BrgKey%5D=PT%3A557aef36614325c2a88b460d&_iepl%5BtargetEntityId%5D=Q%3A557aef36614325c2a88b460d&_iepl%5BinteractionType%5D=questionView)

Up to your hypotheses:

Ad 1) You answered yourself, but the case may be low archaeal diversity within the human body as well as their physiological and biochemical properties which would simply went empty without the proper condition or bacterial community.

Ad 2) The current research suggest that the archaeal organism are as diverse as prokaryotes. For more info I suggest the review of dr. Spang A. et al. It will give you insight on how diverse this domain is.

Article Genomic exploration of the diversity, ecology, and evolution...

Ad 3) There are quite a potent number of archaeal viruses, but it may be the fact, that they quiet nothing-like the bacterial ones. So if you go back to Ad 1), it may be the fact that they may not carry the virulence triggers or factor which would transfrom the organism into a potent pathogen.Article Archaeal Viruses, Not Archaeal Phages: An Archaeological Dig

The fact, we still don´t have the Archaean pathogen is really complex and quiet puzzling. The methanogens as well as some species which are able to thrive on human skin (Ammonia oxidizing haloarchaea, etc...) may play some role.

In fact, the human body is colonized by only 4 known archaean - Methanobrevibacter smithii and oralis from class Methanobacteria, then Methanosphaera stadtmanae and novel specie, the Methanomassiliicoccus lumyniensis. All of them are bound to the digestive tract except the Methanobrevibacter oralis, thriving as a part of a tooth plaque consortium.

The concentration in the population of those methanogens are usually related to the fibre-rich diet, similar to the prevalence in the organisms bound to this type of diet, due to their role in the ecosystem as H2 sink consumers. Also the metabolical states of human health - such are obesity and anorexia are bound to the elevated concentration of methanogens and some experiments in mice suggest that they may play role in energy conservation during digestion of fibre-rich food. Thus they may promote this states.

Speaking about pathogenesis, we may comment the existence of virulence factors in Archaea. At the end of this answer you will find the Cavicchioli´s review, he comments the finding of gen-analogues of some virulence factors which are usually found in bacterial pathogens. That may be due to the horizontal and lateral gene transfer among those two groups. The role and effect remain unclear from what I know.

Crohn disease and many types of GIT cancers and polyps are as well in the game. Even, some methanogens were isolated from muscle and brain abscesses, but the role is not explained. To get some insight on this topic, you may search profile of Vanessa Nkamga, the researcher at Aix-Marseille Université.

The role of the Archaea in the pathogenetic states is discussed and may be not one of the classic Koch ones -> implying that they may play role in a consortium bound pathogenesis. For example Methanobrevibacter oralis in subgingival infectious sites. Also possible role in the caryogenesis chain is discussed.

For further reading I may recommend these reviews, where it is discussed more with scientific background neeeded for this topic.

Cavicchioli: Article Pathogenic Archaea: do they exist?

Weihnberger and Gophna: Article Archaea in and on the Human Body: Health Implications and Fu...

Fantastic answer Martin! Good luck with the dissertation.

1) I fully agree with Matthew for Martin answer! Great!

2) nitrifying Archaea were detected on human skin. That is quite reasonable - ammonia production.