The Gut–Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production

Abstract

Schizophrenia, a severe mental illness affecting about 1% of the population, manifests during young adulthood, leading to abnormal mental function and behavior. Its multifactorial etiology involves genetic factors, experiences of adversity, infection, and gene–environment interactions. Emerging research indicates that maternal infection or stress during pregnancy may also increase schizophrenia risk in offspring. Recent research on the gut–brain axis highlights the gut microbiome’s potential influence on central nervous system (CNS) function and mental health, including schizophrenia. The gut microbiota, located in the digestive system, has a significant role to play in human physiology, affecting immune system development, vitamin synthesis, and protection against pathogenic bacteria. Disruptions to the gut microbiota, caused by diet, medication use, environmental pollutants, and stress, may lead to imbalances with far-reaching effects on CNS function and mental health. Of interest are short-chain fatty acids (SCFAs), metabolic byproducts produced by gut microbes during fermentation. SCFAs can cross the blood–brain barrier, influencing CNS activity, including microglia and cytokine modulation. The dysregulation of neurotransmitters produced by gut microbes may contribute to CNS disorders, including schizophrenia. This review explores the potential relationship between SCFAs, the gut microbiome, and schizophrenia. Our aim is to deepen the understanding of the gut–brain axis in schizophrenia and to elucidate its implications for future research and therapeutic approaches.

Importance of good hosting: reviewing the bi-directionality of the microbiome-gut-brain-axis

“…For instance, Madan et al (2020) reported that depression and anxiety severity in hospitalized patients were negatively associated with gut bacteria alpha-diversity and richness, and that these parameters changed during depression remission at discharge. Altered microbiome diversity and the abundance of specific bacterial genera have also been reported in schizophrenia (see Ju et al, 2023 for review), and some of these observations overlap with findings in mood disorders. Therefore, the role of the gut microbiome in psychiatric disorders is not clear-cut, and there is notable variation in reports of microbiome profiles in any one illness.…”

Neuroinflammation and Schizophrenia: New Therapeutic Strategies through Psychobiotics, Nanotechnology, and Artificial Intelligence (AI)

“…Furthermore, some psychobiotics can act as prebiotics, providing specific substrates that encourage the growth of certain beneficial bacterial species, which, in turn, can contribute to the restoration of the intestinal microbiota balance [8,9]. This modulation of the intestinal environment not only supports digestive health but can also have systemic effects, including improving the intestinal barrier and reducing permeability, which is crucial for preventing the translocation of pro-inflammatory substances that could exacerbate the neuroinflammation observed in patients with schizophrenia [15].…”

Investigating the Impact of Diet, Supplementation, Microbiota, Gut-Brain Axis in Schizophrenia: A Narrative Review

“…SCFAs can cross the blood-brain barrier, where they stimulate cytokine production, modulate microglial activity, and exert an influence on CNS function [74]. Some research suggests that alterations in gut microbiota composition and SCFA production could influence brain function and behavior through the gutbrain axis [75].…”

“…Moreover, butyrate can promote the production of brain-derived neurotrophic factor (BDNF), which enhances neurotransmitter production through the vagus nerve [75]. BDNF is a neurotrophic factor crucial for neurodevelopment, neuroprotection, and the plasticity of glutamatergic and GABAergic synapses.…”