Project Details
Projekt
Fetal Programming of infant microbiome development and consequences for neurodevelopment
Subject Area
Biological Psychology and Cognitive Neuroscience
Personality Psychology, Clinical and Medical Psychology, Methodology
Personality Psychology, Clinical and Medical Psychology, Methodology
Term
since 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 513319150
Disease susceptibility is determined by the dynamic interplay between genetic makeup and environmental conditions, like maternal stress, during intrauterine and early postnatal life (i.e., developmental programming of health and disease). The brain represents a prominent target for developmental programming due to its protracted and active pre- and postnatal development. In particular, alterations in stress-related maternal-placental-fetal (MPF) biological processes appear to play a key role in modifying developmental outcomes generally and offspring brain development specifically. One potential mediator, strongly linked to metabolism, the immune system and to endocrine signaling, is the gut microbiome, which is known to be associated with somatic and psychiatric disorders due to its reciprocal interaction with the brain via the gut-brain axis. While specific microbiome development is known to take place postnatally, the structures (e.g. gastrointestinal tract) which later constitute the microbiome “niche” are established prenatally, and variation like integrity of the gut (e.g., permeability) can be shaped by environmental conditions during pregnancy (e.g., maternal stress). This is likely mediated by variation in MPF endocrine, immune, and metabolic biology, which in the proposed study will be represented by an allostatic load index. Based on this framework, the overarching goal of this project is to elucidate the association of maternal allostatic load during pregnancy with microbiome maturation and neurodevelopment in early life. Towards this goal we aim to first create a model for human gut microbiome maturation (a “microbiome age index”) based on existing data sets, and to use this model to characterize the role of variation in maternal allostatic load during pregnancy in shaping offspring gut microbiota development, as well as to characterize the association between offspring gut microbiota development and neurodevelopment from birth to four years of age. We then plan to explore the role of the gut microbiome as a mediator of the association between allostatic load and neurodevelopment, and to validate observed associations in two external cohorts. We have the opportunity to address these aims in an existing cohort of pregnant women and their fetuses/infants followed from early pregnancy until 24-mo age. We plan to extend this study and seek funding for adding a timepoint for data collection at 48-mo age, a developmental time point when the microbiome is assumed to have stabilized. Our study will contribute to a better understanding which biological cues in early life shape the developing brain, which is key to translating the developmental programming paradigm into novel intervention strategies that are mechanism-informed and harness the unique opportunity of sensitive developmental periods when interventions are most effective.
DFG Programme
Research Grants
