Obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids
Open accessAbstract
The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with obesity.
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Microbial metabolism of aromatic amino acids tryptophan, tyrosine, and phenylalanine and their catabolites was associated with impaired short-term and working memory in mice that received a microbial transplant from obese human subjects.
“For example, it was recently reported that microbial metabolism of the aromatic amino acids tryptophan (precursor of 5-HT), tyrosine, and phenylalanine (both precursors of dopamine) and their catabolites was associated with impaired short-term and working memory in mice that received a microbial transplant from obese human subjects (379).”
From Diet and the Microbiota–Gut–Brain Axis: Sowing the Seeds of Good Mental Health (2021) · cites this paper as [379]
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- Authors
- Arnoriaga-Rodríguez, M., Mayneris-Perxachs, J., Burokas, A., Contreras-Rodríguez, O., Blasco, G., Coll, C., Biarnés, C., Miranda-Olivos, R., Latorre, J., Moreno-Navarrete, J.-M., Castells-Nobau, A., Sabater, M., Palomo-Buitrago, M. E., Puig, J., Pedraza, S., Gich, J., Pérez-Brocal, V., Ricart, W., Moya, A., Fernández-Real, X., Ramió-Torrentà, L., Pamplona, R., Sol, J., Jové, M., Portero-Otin, M., Maldonado, R., & Fernández-Real, J. M.
- Affiliations
- Universitat Pompeu Fabra (ES)
- Institut d'Investigació Biomèdica de Girona (ES)
- Hospital Universitari de Girona Doctor Josep Trueta (ES)
- Parque Sanitario Pere Virgili (ES)
- Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (ES)
- Universitat de Girona (ES)
- École Polytechnique Fédérale de Lausanne (CH)
- Universitat de Lleida (ES)
- Corresponding author
- Maldonado, Rafael
- ORCID
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2020-10
- Volume
- 32
- Issue
- 4
- Pages
- 548-560.e7
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W3091836995
- Cited by
- 157
- References
- 106
- Citations by year
- 2026: 15 · 2025: 26 · 2024: 26 · 2023: 37 · 2022: 28 · 2021: 22 · 2020: 3
- FWCI
- 7.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Metabolism (publishedVersion)
- PubMed (publishedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Department of Health and Social Care (SLT002/16/00250)
- European Regional Development Fund (1.2.2-LMT-K-718-02-0014)
- Seventh Framework Programme (2013-602891)
- Instituto de Salud Carlos III (PI18/01022, PI15/01934, SAF2017-84060-R, SAF2015-65878-R)
- Centro de Investigación Biomédica en Red-Fisiopatología de la Obesidad y Nutrición
- Institució Catalana de Recerca i Estudis Avançats (RD16/0017/0020, 16/0017/0020)
- European Commission
- Ministerio de Ciencia, Innovación y Universidades (RTI2018-099200-B-I00)
- Lietuvos Mokslo Taryba
- Generalitat de Catalunya
- Ministerio de Economía y Competitividad (Prometeo/2018/A/133)
- European Social Fund (CP18/00009, SLT006/17/00236)
- Agència de Gestió d'Ajuts Universitaris i de Recerca (2017-669, SGR2017-669)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- obesity, gut microbiota, short-term memory, working memory, aromatic amino acids, gut microbiota metabolism, microbiota transplantation, hippocampus, frontal cortex, memory impairment, inflammatory genes, fear extinction learning
- MeSH terms
- Gastrointestinal Microbiome, Adult, Aged, Animals, Cross-Sectional Studies, Female, Humans, Magnetic Resonance Imaging, Male, Memory, Short-Term, Mice, Inbred C57BL, Middle Aged, Obesity, Case-Control Studies, Amino Acids, Aromatic, Mice, Metabolomics
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