Guts Imbalance Imbalances the Brain: A Review of Gut Microbiota Association With Neurological and Psychiatric Disorders

Abstract

Over the last 10 years, there has been a growing interest in the relationship between gut microbiota, the brain, and neurologic-associated affections. As multiple preclinical and clinical research studies highlight gut microbiota's potential to modulate the general state of health state, it goes without saying that gut microbiota plays a significant role in neurogenesis, mental and cognitive development, emotions, and behaviors, and in the progression of neuropsychiatric illnesses. Gut microbiota produces important biologic products that, through the gut-brain axis, are directly connected with the appearance and evolution of neurological and psychiatric disorders such as depression, anxiety, bipolar disorder, autism, schizophrenia, Parkinson's disease, Alzheimer's disease, dementia, multiple sclerosis, and epilepsy. This study reviews recent research on the link between gut microbiota and the brain, and microbiome's role in shaping the development of the most common neurological and psychiatric illnesses. Moreover, special attention is paid to the use of probiotic formulations as a potential non-invasive therapeutic opportunity for prevention and management of neuropsychiatric-associated affections.

Keywords: dysbiosis; gut microbiota; gut-brain axis; mental health; microbiome; neuropsychiatric affections; psychobiotics.

FIGURE 1

Microbiota-gut-brain bidirectional relationship. 1. The vagus nerve transfers information on the state of the digestive system to the brain through sensory fibers. It sends neuronal, endocrine, and immune messages to the gut microbiota influencing the state of brain health through various pathways (e.g., by bidirectional vagus nerve-to-brain communication, or through the enteric nervous system (ENS) and enteroendocrine cells with neuropods). Gastrointestinal bioactive molecules (neurotransmitters and hormones, cytokines, and microbial metabolites) also produced under the influence of external factors, such as prebiotics, psychobiotics, drugs, and lifestyle habits, end up in the brain tissue through the blood-brain barrier that consists of endothelial cells of the brain capillary wall, astrocyte end-feet surrounding the capillary, and pericytes embedded in the capillary basement membrane. 2. Hypothalamic-pituitary-adrenal (HPA) axis activation is characterized by the release of corticotropin-releasing hormone (CRH) from the hypothalamus, which then stimulates the delivery of adrenocorticotropic hormone (ACTH) from the anterior pituitary gland. ACTH acts on the adrenal gland to produce and release the stress hormone (cortisol), which is responsible for the modulation of the intestinal epithelial barrier and immune responses. 3. Enteroendocrine cells with neuropods are one of the most important influencers of bidirectional brain-gut communication. The innervation induced to the enterochromaffin-cell signaling to neuronal circuits by the vagus nerve, modulates the pain response, background emotions, immune-response, neurogenesis, and neurodevelopment. The vagus nerve also has immunomodulatory properties and plays an essential role in gastrointestinal and psychiatric disorders (e.g., depression, posttraumatic stress disorder, anxiety) (image created using the BioRender application; https://app.biorender.com).

FIGURE 2

Possible formulations of psychobiotics. Dairy products such as yogurt, milk, and cheese fortified with probiotic strains are among the most consumed food products that have a positive influence on the gastrointestinal tract and have possible beneficial implications in mental health (274). Microencapsulated probiotics and those formulated as powders are commercially available and administered as supplements after antibiotic treatments (275, 276). Cereal-based products are used as vehicles for probiotics delivery (274). Different edible biopolymer-based coatings with entrapped probiotics are developed to facilitate both probiotics consumption and reduction of non-degradable packaging materials (277, 278). Fruits, vegetables, and agro-industrial waste-derived beverages enriched with probiotics are developed for easier probiotic and bioactive compound delivery (264, 279). Edible products supplemented with probiotics maintain gastrointestinal homeostasis and influence neurological health. Deeper studies that consider the impact of probiotic food products as psychobiotics in the prevention and management of mental-associated diseases are needed.