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Gut microbiota links to serum ferritin and cognition.

Department of Diabetes, Endocrinology and Nutrition, Dr. Josep Trueta University Hospital, Girona, Spain. Nutrition, Eumetabolism and Health Group, Girona Biomedical Research Institute (IDIBGI), Girona, Spain. CIBER Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERobn), Madrid, Spain. Neuroimmunology and Multiple Sclerosis Unit, Department of Neurology, Neurodegeneration and Neuroinflammation research group, IDIBGI. Department of Medical Sciences, Dr. Josep Trueta University Hospital, University of Girona, Girona-Salt, Spain. Department of Medical Sciences, School of Medicine, University of Girona, Girona, Spain. Research Group on Health, Gender, and Aging, Girona Biomedical Research Institute (IDIBGI) and University of Girona, Girona, Spain. Department of Nursing, University of Girona, Girona, Spain. Area of Genomics and Health, Foundation for the Promotion of Sanitary and Biomedical Research of Valencia Region (FISABIO-Public Health), Valencia, Spain. Biomedical Research Networking Center for Epidemiology and Public Health (CIBERESP), Madrid, Spain. Institute for Integrative Systems Biology (I2SysBio), University of Valencia and Spanish National Research Council (CSIC), Valencia, Spain. Department of Experimental Medicine, University of Lleida (UdL), Lleida Biomedical Research Institute (IRBLleida), Lleida, Spain. Institute of Diagnostic Imaging (IDI)-Research Unit (IDIR), Parc Sanitari Pere Virgili, Barcelona, Spain. Medical Imaging, Girona Biomedical Research Institute (IdibGi), Girona, Spain. Department of Radiology (IDI), Dr. Josep Trueta University Hospital, Girona, Spain. Vascular Health Research Group of Girona (ISV-Girona), Jordi Gol Institute for Primary Care Research (Institut Universitari per a la Recerca en Atenció Primària Jordi Gol I Gorina -IDIAPJGol), Red de Investigación en Cronicidad, Atención Primaria y Promoción de la Salud -RICAPPS- ISCIII, Girona, Spain. Girona Biomedical Research Institute (IDIBGI), Dr. Josep Trueta University Hospital, Girona, Spain.

Gut microbes. 2023;(2):2290318
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Abstract

Iron is required for the replication and growth of almost all bacterial species and in the production of myelin and neurotransmitters. Increasing clinical studies evidence that the gut microbiota plays a critical role in iron metabolism and cognition. However, the understanding of the complex iron-microbiome-cognition crosstalk remains elusive. In a recent study in the Aging Imageomics cohort (n = 1,030), we identified a positive association of serum ferritin (SF) with executive function (EF) as inferred from the semantic verbal fluency (SVF,) the total digit span (TDS) and the phonemic verbal fluency tests (PVF). Here, we explored the potential mechanisms by analyzing the gut microbiome and plasma metabolome using shotgun metagenomics and HPLC-ESI-MS/MS, respectively. Different bacterial species belonging to the Proteobacteria phylum (Klebsiella pneumoniae, Klebsiella michiganensis, Unclassified Escherichia) were negatively associated both with SF and executive function. At the functional level, an enrichment of microbial pathways involved in phenylalanine, arginine, and proline metabolism was identified. Consistently, phenylacetylglutamine, a metabolite derived from microbial catabolism of phenylalanine, was negatively associated with SF, EF, and semantic memory. Other metabolites such as ureidobutyric acid and 19,20-DiHDPA, a DHA-derived oxylipin, were also consistently and negatively associated with SF, EF, and semantic memory, while plasma eicosapentaenoic acid was positively associated. The associations of SF with cognition could be mediated by the gut microbiome through microbial-derived metabolites.