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

Dementia, a syndrome of cognitive impairment 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 microbiota and its metabolites, such as tryptophan indolic metabolites, short chain fatty acids (SCFAs), and lipopolysaccharides (LPS) could be risk factors for dementia. These functional indicators of the gut microbiota improve our understanding of the role of the gut microbiota in the development of dementia. Only a few epidemiological studies have investigated the association between the circulating levels of these gut microbiota-derived metabolites and the risk of dementia. Further, the interplay between these metabolites and systemic inflammation, and the fact that there is an inflammatory pathogenesis of dementia suggests that the relationship between these metabolites and dementia risk may be influenced by systemic inflammation.Using a cohort of apparently healthy elderly individuals, the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe), we will design a one to two-matched nested case-control study of 777 participants (259 incident dementia cases and 518 controls). These two controls will be selected by random sampling-within risk sets defined by age, sex, blood fasting status, year of blood sampling, and availability of stored blood samples. Frozen pre-dementia blood samples and data on sociodemographic and lifestyle factors at the time of blood sampling will be retrieved. We will profile blood levels of gut microbiota-derived tryptophan indolic metabolites, SCFAs, LPS and LPS binding protein (LBP), and selected proinflammatory cytokines.The current project, entitled “The role of circulating gut MICRObiota-derived MEtabolites in the development of demenTIA (Acronym: MICROMETIA)" aims to (1) investigate independent associations of functional indicators of the gut microbiota, tryptophan indolic metabolites, SCFAs, LPS, and LBP with the risk of dementia and 2) examine the potential mediating and moderating effect of proinflammatory cytokines, CRP and IL-6 on the association of these metabolites with dementia risk.

• DFG Programme: Research Grants