Gut Microbiota in Psychiatric and Neurological Disorders: Current Insights and Therapeutic Implications

Abstract

Recent studies increasingly highlight the complex interaction between gut microbiota and mental health, drawing attention to the role of the microbiota-gut-brain axis (MGBA) in the pathophysiology of mental and neurodevelopmental disorders. Changes in the composition of the gut microbiota-dysbiosis-are associated with conditions such as depression, schizophrenia, bipolar disorder (BD), autism spectrum disorders (ASD), attention deficit hyperactivity disorder (ADHD), and neurodegenerative diseases such as Parkinson's and Alzheimer's. These microbial imbalances can affect brain function through a variety of mechanisms, including activation of the immune system, alteration of intestinal permeability, modulation of the digestive and central nervous systems, and changes in the production of neuroactive metabolites such as short-chain fatty acids, serotonin, and tryptophan derivatives. The aim of this paper is to review the current state of knowledge on therapeutic strategies targeting the gut microbiome-including probiotics, prebiotics, synbiotics, personalized dietary interventions, and fecal microbiota transplantation (FMT)-which are becoming promising adjuncts or alternatives to conventional psychopharmacology, offering a forward-looking and individualized approach to mental health treatment. Understanding the bidirectional and multifactorial nature of MGBA may pave the way for new, integrative treatment paradigms in psychiatry and neurology, requiring further research and exploration of their scope of application.

Keywords: attention-deficit hyperactivity disorder; autism spectrum disorder; bipolar disorder; gut dysbiosis; gut–brain axis; major depressive disorder; microbiota; neurodegenerative disorders; schizophrenia.

Figure 1

Schematic representation of the interrelationships on the gut–brain axis. The gut–brain axis is mediated through multiple direct and indirect pathways. These pathways include: (1) neural routes involving the enteric nervous system (ENS), vagus nerve, and spinal nerves; (2) neuroendocrine signaling, primarily via the hypothalamic–pituitary–adrenal (HPA) axis; (3) immune mechanisms involving cytokines such as IL-1β, IL-6, and TNF-α; and (4) microbiota-derived metabolites and neuroactive compounds, including short-chain fatty acids (SCFAs), neurotransmitters, vitamins, and tryptophan metabolites [2,8,9,10,11].

Figure 2

Selected factors and their impact on the gut microbiota. The composition of the gut microbiota is influenced by a range of factors throughout the lifespan, including dietary patterns (e.g., Western vs. Mediterranean diets), use of medications and supplements (such as probiotics), underlying medical conditions, exposure to environmental pollutants, psychosocial stress, host genetics, and environmental variables such as urban versus rural living and geographical location [2,8,9,17,22].

Figure 3

Dysbiosis of the gut microbiota can disrupt the brain–gut axis and affect mental health through several interconnected processes. These include decreased serotonin production due to impaired tryptophan metabolism and a lack of essential micronutrients; oxidative stress and neuroinflammation caused by increased reactive oxygen species (ROS) and microbial imbalance; disruption in neurotransmitter balance, including reduced inhibitory signals and altered excitatory transmission; dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis, leading to excessive cortisol release and an exaggerated stress response; impairment of the intestinal barrier, allowing endotoxins to enter the bloodstream and trigger immune activation; and vagus nerve dysfunction, which weakens communication between the gut and brain. Together, these factors create a neuroinflammatory environment that may contribute to the development of psychiatric conditions such as depression and anxiety [8,9,10,11,21,26,27,33,34].

Figure 4

Described changes in gut microbiota in Bipolar Disorder, Schizophrenia and Major Depressive Disorder. These imbalances are associated with disrupted metabolism of neurotransmitters like GABA and glutamate, overproduction of lactic acid, mitochondrial dysfunction, and systemic acidosis. Such changes may contribute to neuroinflammation, altered brain pH, and increased risk of mental disorders [15,44,45,46,49,55,56,57,58,59,60,61,62].

Figure 5

Differences due to dietary habits in the functioning of the microbiome and the gut–brain axis. The Mediterranean diet—rich in fruits, vegetables, whole grains, nuts, and olive oil—supports mental well-being through its antioxidant and anti-inflammatory properties. It boosts serotonin production, maintains gut barrier integrity, promotes beneficial bacteria, and increases short-chain fatty acid (SCFA) production. It also helps reduce harmful bacteria like Proteobacteria. In contrast, the Western diet—high in processed foods, sugars, and saturated fats, and low in fiber—is linked to gut dysbiosis, inflammation, and a higher risk of mood disorders. This comparison highlights how diet directly impacts gut health and brain function, playing a key role in mental well-being [58,72,75,78].