Connecting Host–parasite Interactions to the Microbiota–gut–brain Axis

Abstract Purpose of Review To provide a comprehensive overview of the key findings on the microbiota–gut–brain axis. Recent Findings Growing evidence indicates that microbial metabolites, neurotransmitters, cytokines, and gut-derived hormones modulate blood–brain barrier integrity, neuroinflammation, and brain function, while the brain reciprocally shapes gut physiology through neuroendocrine and autonomic pathways. Disruption of this axis by dysbiosis has been implicated in a broad spectrum of disorders, including depression, schizophrenia, neurodevelopmental diseases, and chronic inflammatory conditions. More recently, infectious diseases have emerged as important modulators of the microbiota–gut–brain axis, as pathogens such as Toxoplasma gondii , Plasmodium spp ., Trypanosoma cruzi , and Leishmania spp . induce microbial dysbiosis, intestinal barrier dysfunction, and systemic immune activation that may contribute to neuroinflammation and neurological manifestations. Summary The microbiota-gut-brain axis represents an interorgan communication system that integrates immune, neural, metabolic, and endocrine signals between the gastrointestinal tract and the central nervous system. The gut microbiota, composed of a vast diversity of microorganisms, plays a fundamental role in maintaining host homeostasis and immunity. Evidence indicates that alterations in its composition, such as dysbiosis, can compromise the integrity of the intestinal and the blood-brain barriers, favoring systemic inflammatory and neuroinflammatory processes associated with neurological, psychiatric disorders and infectious diseases. Furthermore, it dictates not only how the gut influences the brain in a steady state or during disease, but also how the brain coordinates the efferent signals to the gut. In this review, we elucidate the role of the microbiota-gut-brain axis in health and host disease and convey recent data showing that an imbalance in microbiota and gut infections could be mediating late effects on the central nervous system, through their direct effects on the gut barrier and immune system.