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As awareness of the microbiome's crucial role in human health grows, it is essential to investigate the diverse inhabitants of the gut microbiota and their contributions to host well-being. This study focuses on the impact of commensal gut protozoa—an often-overlooked microbial group—on human health and disease. Using mouse models of neurodegeneration and in vitro methods, we aim to elucidate the role of commensal gut protozoa in brain health and their influence on neurodegenerative processes. By shedding light on these understudied organisms, we hope to advance our understanding of microbiota dynamics within the gut-brain axis and explore innovative microbiota-based therapies to promote brain health.