A study led by the Girona Biomedical Research Institute Dr. Josep Trueta (IDIBGI) has identified for the first time a significant association between the presence of a microorganism from the archaea group—present in the gut microbiota—and executive brain function in adults. Specifically, the research team observed that high levels of Methanobrevibacter smithii, a species from the archaea domain (Archaea), are linked to better inhibitory control and cognitive flexibility, as well as to a specific gut microbiota composition and beneficial metabolic changes for the brain. The results, published in the scientific journal Gut Microbes, highlight this microorganism as a potential therapeutic target to support brain health, especially in individuals with obesity.
The study combined analytical techniques covering multiple levels of biological regulation (metagenomics and metabolomics) as well as neuropsychological assessments in over 1,000 people. Analyses were based on two large population cohorts: the IRONMET cohort (125 participants) and the Ageing Imagenome cohort (942 participants).
“The results show that individuals with a high abundance of M. smithii in the gut score better on executive function tests, which include abilities such as planning, inhibition, and cognitive flexibility—all of which have a major impact on daily life,” notes Dr. Jordi Mayneris-Perxachs, head of the IDIBGI’s Integrative Systems Medicine and Biology research group and corresponding co-author of the article. Additionally, individuals with high levels of M. smithii in their gut also had a specific gut microbiota composition. “Studies like this highlight the importance of integrating multiple layers of biological data to understand how the microbiota can influence complex functions such as cognition,” adds Mayneris-Perxachs.
Archaea, often overlooked in gut microbiota studies, are microorganisms belonging to a domain distinct from bacteria, with unique cell structures and an extraordinary ability to withstand extreme conditions. In the human gut, the most common archaea are methanogens such as M. smithii.
“This work shows that certain microbiota members, like archaea, may play a functional role in brain health. It is an important step toward a deeper understanding of the gut-brain axis beyond bacteria,” explains Dr. José Manuel Fernández-Real, head of the Nutrition, Eumetabolism and Health research group at IDIBGI and CIBERObn, and corresponding co-author of the paper. Dr. Fernández-Real is also Head of the Endocrinology Department at the Dr. Josep Trueta Hospital and Dean and Professor at the University of Girona.
“It is important to continue investigating the role of different species that make up the gut microbiota, to understand how they interact with each other, and which ones contribute the most to the metabolic changes that may affect cognition and overall health,” says Andrea Fumagalli, first author of the article and predoctoral researcher at IDIBGI within the European SmartAge project.
This study, led by IDIBGI, also involved research teams from the Foundation for the Promotion of Health and Biomedical Research of the Valencian Community (Fisabio) - CIBERESP, as well as from Pompeu Fabra University. The latter team conducted mouse experiments to study the direct effects of this microorganism on behaviour and brain metabolism. Transplanting microbiota from donors with high levels of M. smithii led to improved cognitive flexibility and reduced body weight in recipient mice. These results align with the findings from the human analyses.
The study opens a new avenue for research on the gut-brain relationship, underscoring the importance of exploring not only bacteria but also other members of the gut microbiota, such as archaea, which may play a key role in mental and metabolic health. The findings also suggest that this archaeal species could be considered a potential therapeutic target for improving executive brain function, especially in individuals with obesity, who tend to have lower inhibitory control.
The European project SmartAge: "Gut-brain-axis: Targets for improvement of cognition in the elderly" has received funding from the Horizon 2020 Framework Programme of the European Union, under the Marie Skłodowska-Curie Innovative Training Network grant agreement No 859890.
Reference article: Fumagalli A, Castells-Nobau A, Trivedi D, Garre-Olmo J, Puig J, Ramos R, Ramió-Torrentà L, Pérez-Brocal V, Moya A, Swann J, Martin-Garcia E, Maldonado R, Fernández-Real JM, Mayneris-Perxachs J. Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism. Gut Microbes. 2025 Dec;17(1):2455506. doi: 10.1080/19490976.2025.2455506. Epub 2025 Feb 5. PMID: 39910065; PMCID: PMC11810085.
