Dr. Ávila-Macaya, Ariel

During the last years, accumulating evidence has suggested that the gut microbiota plays a key role in the pathogenesis of neurodevelopmental and neurodegenerative diseases via the gut–brain axis. Moreover, current research has helped to elucidate different communication pathways between the gut microbiota and neural tissues (e.g., the vagus nerve, tryptophan production, extrinsic enteric-associated neurons, and short chain fatty acids). On the other hand, altering the composition of gut microbiota promotes a state known as dysbiosis, where the balance between helpful and pathogenic bacteria is disrupted, usually stimulating the last ones. Herein, we summarize selected findings of the recent literature concerning the gut microbiome on the onset and progression of neurodevelopmental and degenerative disorders, and the strategies to modulate its composition in the search for therapeutical approaches, focusing mainly on animal models studies. Readers are advised that this is a young field, based on early studies, that is rapidly growing and being updated as the field advances.

The development of the brain is shaped by a myriad of factors among which neurotransmitters play remarkable roles before and during the formation and maturation of synaptic circuits. Cellular processes such as neurogenesis, morphological development, synaptogenesis and maturation of synapses are temporary and spatially regulated by the local or distal influence of neurotransmitters in the developing cortex. Thus, research on this area has contributed to the understanding of fundamental mechanisms of brain development and to shed light on the etiology of various human neurodevelopmental disorders such as autism and Rett syndrome (RTT), among others. Recently, the field of neuroscience has been shaken by an explosive advance of experimental approaches linked to the use of induced pluripotent stem cells and reprogrammed neurons. This new technology has allowed researchers for the first time to model in the lab the unique events that take place during early human brain development and to explore the mechanisms that cause synaptopathies. In this context, the role of neurotransmitters during early stages of cortex development is beginning to be re-evaluated and a revision of the state of the art has become necessary in a time when new protocols are being worked out to differentiate stem cells into functional neurons. New perspectives on reconsidering the function of neurotransmitters include opportunities for methodological advances, a better understanding of the origin of mental disorders and the potential for development of new treatments.