From microbes to mind: germ-free models in neuropsychiatric research

The gut-microbiota-brain axis refers to the bidirectional communication system between the gut, its microbial community, and the brain. This interaction involves a complex interplay of neural pathways, chemical transmitters, and immunological mechanisms. Germ-free animal models have been extensively employed to investigate gut-microbiota-brain interactions, significantly contributing to our current understanding of the role of intestinal microbes in brain function. However, despite the many benefits, this absence of microbiota is not futile. Germ-free animals present physiological and neurodevelopmental alterations that can persist even after reconstitution with normal microbiota. Therefore, the main goal of this minireview is to discuss how some of the inherent limitations of this model can interfere with the conclusion obtained when using these animals to study the complex nature of neuropsychiatric disorders. Furthermore, we examine the inclusion and use of antibiotic-based treatments as an alternative in the research of gut-brain interactions.