Nutritional iron deficiency effects on microbiota-gut-brain axis

Abstract

Iron deficiency (ID) is the most frequent nutritional deficiency in the world. While it is clear that nutritional ID has an impact on the metabolism and cellular biochemistry of gut bacteria, the potential implications in the microbiota-gut-brain axis (MGB) are poorly understood. Indeed, dysbiosis in the gut microbiota, observed in early-life ID, is associated with neurodevelopmental impairments, including autism spectrum disorder and attention deficit hyperactivity disorder. Understanding the effects of ID on bacterial signaling offers avenues for targeted interventions to mitigate neurodevelopmental risks in iron deficient populations. In this study, we investigated the responses of two representative bacterial species of human microbiota, Escherichia coli (E. coli) and Limosilactobacillus reuteri (L. reuteri), to experimental conditions of ID. Using the iron chelator 2,2’-Bipyridyl (BP), we developed a reliable method for the creation of in-vitro ID conditions on bacteria cells. Then, we assessed and mathematically modelled their growth and cultivability, and we explored the bioelectric profile (electroma) of these bacteria as a potential way of communication with host neurons, using the voltage-sensitive fluorescent dye DiBAC4(3). Our findings revealed that E. coli and L. reuteri behave differentially in response to ID in their culture environment: whereas L. reuteri showed no alterations in growth dynamics neither cultivability when treated with BP, E. coli showed clear decreases in the growth rate and cultivability when affected by ID. Interestingly, only E. coli demonstrated an altered bioelectric profile under conditions of ID, characterized by increased depolarization of cells. Our observations underscore the heterogeneity of bacterial responses to iron deficiency and highlight the complexity of interactions within the gut microbiota. Understanding such variability is crucial for deciphering the role of microbiota in health and disease, particularly in conditions associated with nutritional iron imbalance and neurological disorders.