We've made significant progress in our RADIOGUT project, which studies how early-life gut microbes influence brain development. We focused on two main areas: how changes in gut microbes during pregnancy affect brain cells and how these changes might impact the communication between the maternal gut microbes and the developing brain.
During our research, we've conducted experiments on which included both embryos and early postnatal mice in the context of a disrupted normal gut microbiota. We observed the effects on brain development at various stages of embryonic development and after birth. Our findings suggest that, at least in mice, a mother's gut microbes during pregnancy directly influence the development of her offspring's brain cells, particularly in a structure called the choroid plexus, which is involved in producing the fluid surrounding the brain and spinal cord. We also noticed differences between male and female embryos, even at the early stages of development. We also observed changes in specific brain cells known as radial glial cells, which play a key role in brain development. These changes were linked to the mother’s gut microbiota srarus. We also noticed that different regions of the brain, like the cortex and more ancient brain areas like the hypothalamus and amygdala (more involved in emotions and hormone regulation), were affected in distinct ways. Overall, this supports our theory that gut microbes during pregnancy can influence how the brain develops.
We also studied the protective barriers of the developing brain, particularly in a structure named the choroid plexus, which helps regulate what substances can enter the brain. We found changes in the integrity of these barriers when the mother's gut microbes were disrupted. This suggests that the gut microbes may also play a role in how the brain protects itself during development. We are now investigating whether these changes could contribute to brain development and how they might relate to brain disorders.
We also identified several chemical changes in the blood and brain fluid of embryos, which were linked to changes in the mother's gut microbiota. For instance, a brain chemical called N-acetylaspartate (NAA), which is important for brain health, was found to decrease when the mother’s gut bacteria were disrupted. We are now working to understand how these changes might impact brain development.
In terms of technological and methodological advancements, we have developed several new techniques:
- A method to extract and study cerebrospinal fluid from embryos, which helps us understand which signals from the maternal gut could reach the embryonic brain, thereby influencing brain cells and their development.
- We also created a cellular model consisting of cells cultured in a dish, which helps us to study the brain’s protective barriers ex vivo. We can culture these cells in different conditions, for example adding specific microbial signals of interest, that have the potential to modulate the brain barriers.
- Embryonic brain tissue preparation: we have optimised methods of embryonic tissue processing, specific to the study of the different brain structures of interest for our studies.
- Working with Germ-Free Animals: To ensure our results are accurate, we used a special group of animals that were completely free of gut bacteria. This allowed us to closely study the role of maternal gut bacteria in brain development.
