The role of circulating gut MICRObiota-derived MEtabolites in the development of demenTIA (Acronym: MICROMETIA)

• Applicant: Kolade Oluwagbemigun, Ph.D.
• Subject Area: Epidemiology and Medical Biometry/Statistics ; Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2021 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 460591722

• Final Report Year: 2024

Final Report Abstract

Dementia is a neurodegenerative disease characterized by cognitive impairment that affects memory, cognitive abilities, and behaviour, and significantly interferes with a person’s ability to perform daily activities. Dementia is still a major and increasing public health problem. Extensive efforts continue to be expended on early detection, treatment, prevention, and identification of risk factors of dementia. The gut microbiome and its molecules, particularly indole-containing tryptophan metabolites, short chain fatty acids (SCFAs), and lipopolysaccharides could be risk factors and/or biomarkers for dementia. Indeed, these molecules, which are functional indicators of the gut microbiome, may provide additional insights into the role of the gut microbiome in the development of dementia. Only a few epidemiological studies have investigated the association between the circulating levels of these gut microbiome molecules and the risk of dementia. Further, the inflammatory pathogenesis of dementia and the fact that there is interplay between these molecules and systemic inflammation suggests that the relationship between these molecules and dementia risk may be influenced by systemic inflammation. This project was a population-based epidemiological investigation of 805 apparently healthy elderly individuals (83 years, 66% women) free of dementia at baseline from the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe). The project aimed to uncover potential associations of 19 selected gut microbiome molecules comprising lipopolysaccharide and its binding protein (LPB), SCFAs, and indole-containing tryptophan metabolites as well as four inflammatory biomarkers with the risk of dementia in a case-cohort design. The pre-dementia blood levels of these molecules were quantified with well-validated laboratory methodologies and their concentration was linked to incident all-cause dementia (ACD) and Alzheimer’s disease dementia (AD) using conventional and classical statistical methods and machine learning techniques. The findings from this study could contribute to evidencebased decision-making in the prevention, treatment, and management of dementia.

Publications

• Exploring the Association between Habitual Food Intake and the Urine and Blood Metabolome in Adolescents and Young Adults: A Cohort Study. Molecular Nutrition & Food Research, 66(18).
  Brachem, Christian; Oluwagbemigun, Kolade; Langenau, Julia; Weinhold, Leonie; Alexy, Ute; Schmid, Matthias & Nöthlings, Ute
  
• An Investigation into the Relationship of Circulating Gut Microbiome Molecules and Inflammatory Markers with the Risk of Incident Dementia in Later Life. Molecular Neurobiology, 61(12), 9776-9793.
  Oluwagbemigun, Kolade; Anesi, Andrea; Vrhovsek, Urska; Mattivi, Fulvio; Martino, Adami Pamela; Pentzek, Michael; Scherer, Martin; Riedel-Heller, Steffi G.; Weyerer, Siegfried; Bickel, Horst; Wiese, Birgitt; Schmid, Matthias; Cryan, John F.; Ramirez, Alfredo; Wagner, Michael & Nöthlings, Ute
  
• Exploring the association of physical activity with the plasma and urine metabolome in adolescents and young adults. Nutrition & Metabolism, 20(1).
  Muli, Samuel; Brachem, Christian; Alexy, Ute; Schmid, Matthias; Oluwagbemigun, Kolade & Nöthlings, Ute
  
• Replication and mediation of the association between the metabolome and clinical markers of metabolic health in an adolescent cohort study. Scientific Reports, 13(1).
  Brachem, Christian; Weinhold, Leonie; Alexy, Ute; Schmid, Matthias; Oluwagbemigun, Kolade & Nöthlings, Ute
  
• Environmental sustainability of diets among children and adolescents in the German DONALD cohort study: age and time trends, and nutrient adequacy. The American Journal of Clinical Nutrition, 120(1), 92-101.
  van de Locht, Karen; Perrar, Ines; Paris, Juliana Minetto Gellert; Schnermann, Maike Elena; Oluwagbemigun, Kolade; Alexy, Ute & Nöthlings, Ute
  
• Identification and Replication of Urine Metabolites Associated With Short-Term and Habitual Intake of Sweet and Fatty Snacks in European Children and Adolescents. The Journal of Nutrition, 154(11), 3274-3285.
  Goerdten, Jantje; Muli, Samuel; Rattner, Jodi; Merdas, Mira; Achaintre, David; Yuan, Li; De Henauw, Stefaan; Foraita, Ronja; Hunsberger, Monica; Huybrechts, Inge; Lissner, Lauren; Molnár, Dénes; Moreno, Luis A.; Russo, Paola; Veidebaum, Toomas; Aleksandrova, Krasimira; Nöthlings, Ute; Oluwagbemigun, Kolade; Keski-Rahkonen, Pekka & Floegel, Anna
  
• Individual‐Level Drivers of Food Choices and Diet Quality Among Adolescents in Urban West Africa: Evidence From Accra, Ghana. Maternal & Child Nutrition, 21(2).
  Klemm, Janosch; Muli, Samuel; Oluwagbemigun, Kolade; Parlasca, Martin; Crentsil, Aba; Ogum, Deda; Quartey, Peter; Laar, Amos; Lartey, Anna; Borgemeister, Christian & Nöthlings, Ute
  
• Metabolomics signatures of sweetened beverages and added sugar are related to anthropometric measures of adiposity in young individuals: results from a cohort study. The American Journal of Clinical Nutrition, 120(4), 879-890.
  Muli, Samuel; Schnermann, Maike E.; Merdas, Mira; Rattner, Jodi; Achaintre, David; Perrar, Ines; Goerdten, Jantje; Alexy, Ute; Scalbert, Augustin; Schmid, Matthias; Floegel, Anna; Keski-Rahkonen, Pekka; Oluwagbemigun, Kolade & Nöthlings, Ute