When it comes to studies of the human microbiota, bacteria and fungi have historically soaked up most of the limelight. The human archaeome has received little attention, despite the ability of archaea to colonize the gastrointestinal tract, skin, breast milk, urinary tract, lungs, and various other organs. 

Colonization with archaea can occur from mother to child by the transfer of breast milk or by the consumption of dairy products, salty foods, fermented foods, and organic produce.

 

 

Picking apart archaea

 

In 1990, Woese, Kandler, and Wheelis proposed the three domains of cellular life: archaea, bacteria, and eukarya.

Woese CR, Kandler O, Wheelis ML. Towards a natural system of organisms: proposal for the domains Archaea, Bacteria, and Eucarya. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4576–4579.

This paradigm is now taught in all biology texts.

van der Gulik PTS, Hoff WD, Speijer D. In defence of the three-domains of life paradigm. BMC Evol Biol. 2017 Sep 19;17(1):218.

Archaea are unicellular microorganisms long thought of as “extreme bacteria.” According to a landmark review of archaea published in the World Journal of Gastroenterology, some Archaea are extremophiles, although many are mesophiles that permeate the environment.

Gaci N, Borrel G, Tottey W, et al. Archaea and the human gut: new beginning of an old story. World J Gastroenterol. 2014 Nov 21;20(43):16062–16078.

 

 

 

Methanogens

 

Methanogenic archaea were first identified in the gut more than 40 years ago. They were detected as methane in the breath and isolated into two species: Methanobrevibacter smithii and Methanosphaera stadtmanae.

Gaci N, Borrel G, Tottey W, et al. Archaea and the human gut: new beginning of an old story. World J Gastroenterol. 2014 Nov 21;20(43):16062–16078.

 

Between 90% and 99% of gut archaea are methanogens, and methanogenic archaea make up about 10% of the entire anaerobic community. In humans, the number of methanogens increases with age. The diversity of methanogens is most pronounced in children and the elderly.

Cisek AA, Szymańska E, Aleksandrzak-Piekarczyk T, et al. The role of methanogenic archaea in inflammatory bowel disease—A review. J Pers Med. 2024 Feb 10;14(2):196.

 

M. smithii uses H2 (or formate) to reduce CO2, and M. stadtmanae uses H2 to reduce methanol. M. smithii  colonizes the gastrointestinal tract from the cecum to the rectum, whereas M. smithii  colonizes the distal colon.

Gaci N, Borrel G, Tottey W, et al. Archaea and the human gut: new beginning of an old story. World J Gastroenterol. 2014 Nov 21;20(43):16062–16078.

 

Methanogens exist at the end of the food chain and play a role in different energy conservation systems. The only energetic metabolism of methanogens is methanogenesis. Methanogenesis includes a small number of substrates derived from anaerobic degradation of organic matter by hydrolytic and fermentative bacteria.

Gaci N, Borrel G, Tottey W, et al. Archaea and the human gut: new beginning of an old story. World J Gastroenterol. 2014 Nov 21;20(43):16062–16078.

 

 

GI disease

 

The review authors summarized some of the findings at the time of publication:

Gaci N, Borrel G, Tottey W, et al. Archaea and the human gut: new beginning of an old story. World J Gastroenterol. 2014 Nov 21;20(43):16062–16078.

 

M. stadtmanae was shown to be more common in patients with IBD. In healthy individuals, it stimulates production of TNF, an inflammatory cytokine, but patients with IBD were found to have a higher circulating IgG response to M. stadtmanae.

The associations between methanogens and colorectal cancer were mixed. For instance, in one study, 80% of colorectal cancer patients were found to be methane producers, and another reported that methane production increases with the severity of the disease. However, no significant relationship between the amount of breath methane and colorectal cancer was observed. A study in native Africans, who harbor a high level of methanogenic archaea, were found to be at lower risk for sporadic colorectal cancer. 

Here are some other research findings relating methanogens to health:

• People with obesity have higher levels of methanogens and lower levels of M. smithii.

• People with anorexia have higher levels of M. smithii. 

• People with diverticulosis have higher levels of methanogens.

Experts writing about archaea in the human microbiome examined the association with small intestinal bacterial overgrowth (SIBO).

Duller S, Moissl-Eichinger C. Archaea in the human microbiome and potential effects on human infectious disease. Emerging Infect Dis. 2024;30(8):1505–1513.

In SIBO, there is an overgrowth of bacteria (>100,000 colony-forming units). This is typically due to gram-negative anaerobic bacteria and demonstrated by a hydrogen-positive breath test. One study, however, detected an overgrowth of archaea in 30% of cases.

 

 

“Conversely, hydrogenic SIBO is associated with higher occurrences of symptoms like diarrhea, cholecystectomy, diabetes, and Roux-en-Y gastric bypass surgery,” the authors wrote. “Those distinctions may arise from varying sensitivities of archaeal physiology to host factors, including gut anatomy, motility, luminal bile acid concentration, and the capacity to synthesize or salvage cobalamin from neighboring microbiota or diet.”

 

Archaebiotics

 

Although there isn’t any recent research on the topic, the prospect of archaebiotics has been proposed in the literature.

Brugère JF, Borrel G, Gaci N, et al. Archaebiotics: proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease. Gut Microbes. 2014 Jan-Feb;5(1):5–10.

 

Trimethylamine (TMA) is produced by gut bacteria from ingredients found in the diet. TMA has a characteristic fishy smell, and therefore its presence in the body is associated with trimethylaminuria (TMAU), or fish-odor syndrome. Individuals prone to TMAU have a genetic defect that prevents production of flavin-containing monooxygenase 3, an enzyme which converts TMA into trimethylamine oxide (TMAO) in the liver. TMA metabolism by intestinal microbiota may affect atherosclerosis risk through modulation of TMAO production. TMAO is a risk factor for cardiovascular disease in humans.

An archaebiotic that could reduce TMA formation in the gut might potentially prevent or attenuate some metabolic disorders. An experiment with Methanomassiliicoccus showed that it could deplete TMA, by reducing it with H2 for methanogenesis.

Brugère JF, Borrel G, Gaci N, et al. Archaebiotics: proposed therapeutic use of archaea to prevent trimethylaminuria and cardiovascular disease. Gut Microbes. 2014 Jan-Feb;5(1):5–10.