The Role of Gut Dysbiosis in the Pathophysiology of Neuropsychiatric Disorders

Mounting evidence shows that the complex gut microbial ecosystem in the human gastrointestinal (GI) tract regulates the physiology of the central nervous system (CNS) via microbiota and the gut-brain (MGB) axis. The GI microbial ecosystem communicates with the brain through the neuroendocrine, immune, and autonomic nervous systems. Recent studies have bolstered the involvement of dysfunctional MGB axis signaling in the pathophysiology of several neurodegenerative, neurodevelopmental, and neuropsychiatric disorders (NPDs). Several investigations on the dynamic microbial system and genetic-environmental interactions with the gut microbiota (GM) have shown that changes in the composition, diversity and/or functions of gut microbes (termed gut dysbiosis (GD)) affect neuropsychiatric health by inducing alterations in the signaling pathways of the MGB axis. Interestingly, both preclinical and clinical evidence shows a positive correlation between GD and the pathogenesis and progression of NPDs. Long-term GD leads to overstimulation of hypothalamic-pituitary-adrenal (HPA) axis and the neuroimmune system, along with altered neurotransmitter levels, resulting in dysfunctional signal transduction, inflammation, increased oxidative stress (OS), mitochondrial dysfunction, and neuronal death. Further studies on the MGB axis have highlighted the significance of GM in the development of brain regions specific to stress-related behaviors, including depression and anxiety, and the immune system in the early life. GD-mediated deregulation of the MGB axis imbalances host homeostasis significantly by disrupting the integrity of the intestinal and blood-brain barrier (BBB), mucus secretion, and gut immune and brain immune functions. This review collates evidence on the potential interaction between GD and NPDs from preclinical and clinical data. Additionally, we summarize the use of non-therapeutic modulators such as pro-, pre-, syn- and post-biotics, and specific diets or fecal microbiota transplantation (FMT), which are promising targets for the management of NPDs.

Automated summary

Mounting evidence suggests that the gut microbial ecosystem in the human gastrointestinal tract plays a crucial role in regulating the central nervous system through the gut-brain axis. Dysfunctional signaling in the gut-brain axis has been linked to various neurodegenerative, neurodevelopmental, and neuropsychiatric disorders. Changes in gut microbes, known as gut dysbiosis, have been found to affect neuropsychiatric health by altering signaling pathways in the gut-brain axis. Long-term gut dysbiosis can lead to overstimulation of the hypothalamic-pituitary-adrenal axis and neuroimmune system, resulting in inflammation, oxidative stress, mitochondrial dysfunction, and neuronal death. The integrity of the intestinal and blood-brain barrier, as well as gut and brain immune functions, is also disrupted. This review highlights the potential interaction between gut dysbiosis and neurodegenerative, neurodevelopmental, and neuropsychiatric disorders and discusses non-therapeutic strategies for their management.