CLIMATE CHANGES AND REDUCTION OF FOOD MICRONUTRIENTS AVAILABILITY: A MULTI-OMICS APPROACH FOR ANALYZING THE IMPACT OF IRON DEFICIENCY ON THE NERVOUS SYSTEM

Climate change is intensifying global micronutrient deficiencies, with far-reaching implications for both human health and environmental stability. Among these, iron deficiency (ID) is particularly critical due to its essential role in systemic and neurobiological functions. This doctoral research investigates the impact of ID on the nervous system using a multi-omics approach, emphasizing the interplay between gut bacteria and enteric neurons (ENS). The first part of the study examines the effects of ID on Escherichia coli (E. coli) NCTC 9001 and Limosilactobacillus reuteri (L. reuteri) F275 ATCC 23272, two bacterial species representatives of the human gut microbiota. By employing mass spectrometry, we confirmed that the iron chelator 2,2’-bipyridyl (BP) induces ID in E. coli. Our findings reveal that E. coli growth is inhibited under iron-deficient conditions, while L. reuteri remains unaffected. Furthermore, we demonstrated that ID triggers a bioelectric response in E. coli, characterized by bacterial depolarization proportional to iron scarcity. This bioelectric response was absent in L. reuteri, highlighting species-specific adaptations to iron availability. A mathematical model was developed to describe E. coli growth dynamics in relation to BP concentration, offering a predictive framework applicable to other bacterial species. The second part of the study establishes an innovative in vitro co-culture model of mouse enteric neurons (T0297 cell line) and E. coli to explore the effects of iron-deficient bacteria on neuronal cells. E. coli grown under control (CTR) and iron-deficient (ID) conditions was co-cultured with neurons to assess bacterial interaction and neuronal response. Results show that ID bacteria exhibit reduced adhesion and invasion compared to CTR ones, as confirmed by confocal microscopy. Co-culture with ID bacteria modulates neuronal activity, altering cytoplasmic calcium dynamics under basal conditions and in response to neurotransmitter stimulation, while neuronal gene expression remained largely unaffected. Additionally, neuronal morphology and protein expression were unaltered by co-culture with ID bacteria. This research sheds light on the intricate relationship between micronutrient availability, gut microbiota, and the nervous system. By linking ID to bioelectric and functional changes in bacteria and neurons, the findings emphasize the importance of addressing micronutrient deficiencies to protect gut-brain axis health in the context of environmental change.