Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism
The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, n = 125). I...
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Taylor & Francis Group
2025-12-01
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| Series: | Gut Microbes |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/19490976.2025.2455506 |
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| author | Andrea Fumagalli Anna Castells-Nobau Dakshat Trivedi Josep Garre-Olmo Josep Puig Rafel Ramos Lluís Ramió-Torrentà Vicente Pérez-Brocal Andrés Moya Jonathan Swann Elena Martin-Garcia Rafael Maldonado José Manuel Fernández-Real Jordi Mayneris-Perxachs |
| author_facet | Andrea Fumagalli Anna Castells-Nobau Dakshat Trivedi Josep Garre-Olmo Josep Puig Rafel Ramos Lluís Ramió-Torrentà Vicente Pérez-Brocal Andrés Moya Jonathan Swann Elena Martin-Garcia Rafael Maldonado José Manuel Fernández-Real Jordi Mayneris-Perxachs |
| author_sort | Andrea Fumagalli |
| collection | DOAJ |
| description | The relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, n = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly Methanobrevibacter smithii (M. smithii). Stratifying individuals by median-centered log ratios (CLR) of M. smithii (low and high M. smithii groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA p = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, n = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, n = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. M. smithii seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity. |
| format | Article |
| id | doaj-art-03a6df37aa744c569ff5cee9842af217 |
| institution | Kabale University |
| issn | 1949-0976 1949-0984 |
| language | English |
| publishDate | 2025-12-01 |
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| series | Gut Microbes |
| spelling | doaj-art-03a6df37aa744c569ff5cee9842af2172025-02-06T04:14:50ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2455506Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolismAndrea Fumagalli0Anna Castells-Nobau1Dakshat Trivedi2Josep Garre-Olmo3Josep Puig4Rafel Ramos5Lluís Ramió-Torrentà6Vicente Pérez-Brocal7Andrés Moya8Jonathan Swann9Elena Martin-Garcia10Rafael Maldonado11José Manuel Fernández-Real12Jordi Mayneris-Perxachs13Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, SpainSchool of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UKserra-hunter program Department of Nursing, University of Girona, Girona, SpainDepartment of Medical Sciences, School of Medicine, University of Girona, Girona, SpainDepartment of Medical Sciences, School of Medicine, University of Girona, Girona, SpainDepartment of Medical Sciences, School of Medicine, University of Girona, Girona, SpainArea of Genomics and Health, Foundation for the Promotion of Sanitary and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, SpainArea of Genomics and Health, Foundation for the Promotion of Sanitary and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, SpainSchool of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UKLaboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, SpainLaboratory of Neuropharmacology, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, SpainDepartment of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, SpainThe relationship between bacteria, cognitive function and obesity is well established, yet the role of archaeal species remains underexplored. We used shotgun metagenomics and neuropsychological tests to identify microbial species associated with cognition in a discovery cohort (IRONMET, n = 125). Interestingly, methanogen archaeas exhibited the strongest positive associations with cognition, particularly Methanobrevibacter smithii (M. smithii). Stratifying individuals by median-centered log ratios (CLR) of M. smithii (low and high M. smithii groups: LMs and HMs) revealed that HMs exhibited better cognition and distinct gut bacterial profiles (PERMANOVA p = 0.001), characterized by increased levels of Verrucomicrobia, Synergistetes and Lentisphaerae species and reduced levels of Bacteroidetes and Proteobacteria. Several of these species were linked to the cognitive test scores. These findings were replicated in a large-scale validation cohort (Aging Imageomics, n = 942). Functional analyses revealed an enrichment of energy, butyrate, and bile acid metabolism in HMs in both cohorts. Global plasma metabolomics by CIL LC-MS in IRONMET identified an enrichment of methylhistidine, phenylacetate, alpha-linolenic and linoleic acid, and secondary bile acid metabolism associated with increased levels of 3-methylhistidine, phenylacetylgluamine, adrenic acid, and isolithocholic acid in the HMs group. Phenylacetate and linoleic acid metabolism also emerged in the Aging Imageomics cohort performing untargeted HPLC-ESI-MS/MS metabolic profiling, while a targeted bile acid profiling identified again isolithocholic acid as one of the most significant bile acid increased in the HMs. 3-Methylhistidine levels were also associated with intense physical activity in a second validation cohort (IRONMET-CGM, n = 116). Finally, FMT from HMs donors improved cognitive flexibility, reduced weight, and altered SCFAs, histidine-, linoleic acid- and phenylalanine-related metabolites in the dorsal striatum of recipient mice. M. smithii seems to interact with the bacterial ecosystem affecting butyrate, histidine, phenylalanine, and linoleic acid metabolism with a positive impact on cognition, constituting a promising therapeutic target to enhance cognitive performance, especially in subjects with obesity.https://www.tandfonline.com/doi/10.1080/19490976.2025.2455506Microbiotacognitionarchaeacognitive flexibilityexecutive function |
| spellingShingle | Andrea Fumagalli Anna Castells-Nobau Dakshat Trivedi Josep Garre-Olmo Josep Puig Rafel Ramos Lluís Ramió-Torrentà Vicente Pérez-Brocal Andrés Moya Jonathan Swann Elena Martin-Garcia Rafael Maldonado José Manuel Fernández-Real Jordi Mayneris-Perxachs Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism Gut Microbes Microbiota cognition archaea cognitive flexibility executive function |
| title | Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism |
| title_full | Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism |
| title_fullStr | Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism |
| title_full_unstemmed | Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism |
| title_short | Archaea methanogens are associated with cognitive performance through the shaping of gut microbiota, butyrate and histidine metabolism |
| title_sort | archaea methanogens are associated with cognitive performance through the shaping of gut microbiota butyrate and histidine metabolism |
| topic | Microbiota cognition archaea cognitive flexibility executive function |
| url | https://www.tandfonline.com/doi/10.1080/19490976.2025.2455506 |
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