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Schizophrenia: What is the role of the gut-brain axis?

The gut-brain axis in schizophrenia has emerged as a promising area of research, offering new insights into the causes and treatment of this disease. Schizophrenia is known to typically manifest during adulthood, resulting in significant mental and behavioral dysfunctions. Its multifactorial etiology involves genetic factors, experiences of adversity, and gene-environment interactions. Moreover, recent research suggests that infections or maternal stress during pregnancy can increase the risk of schizophrenia. 


Gut and Schizophrenia

The latest research on the gut-brain axis highlights the gut microbiome's influence on the central nervous system (CNS) function and mental health. The gut microbiome, located in the digestive system, plays a crucial role in human physiology, affecting the development of the immune system, synthesis of vitamins, and protection against pathogenic bacteria. Changes in the gut microbiome, caused by diet, medication use, environmental pollutants, and stress, can lead to imbalances with significant effects on CNS function and mental health.


A particular aspect of interest is short-chain fatty acids (SCFAs), metabolic byproducts produced by intestinal microbes during fermentation. These SCFAs can cross the blood-brain barrier, influencing CNS activity and modulating microglia and cytokines. The dysfunction of neurotransmitters produced by intestinal microbes may contribute to CNS disorders, including schizophrenia.


Microbiome and Schizophrenia

Recent studies point to dysbiosis of the gut microbiome in patients with schizophrenia and related disorders. Comparing the metabolic processes involving glucose and lipids of SCFA-producing bacteria and the gut microbiome of schizophrenia patients with healthy individuals, a lower abundance of SCFA-producing bacteria and abnormal glucose and lipid metabolism in the gut microbiome of patients was observed. Additionally, schizophrenia patients exhibited a higher abundance of anaerobic bacteria and bacteria associated with the oral cavity in the gut compared to healthy controls. They were notably, transplanting Streptococcus vestibularis, an oral bacterium, into mice led to the development of schizophrenia-like behavior.


Moreover, changes in cytokine levels were observed in schizophrenia patients compared to healthy individuals. These changes included the elevation of some cytokines and the reduction of others, revealing an association between the composition of the gut microbiome and the cytokine profile in schizophrenia patients. These alterations in the gut microbiome also reduced the activity of N-methyl-D-aspartate (NMDA) receptors and brain-derived neurotrophic factors (BDNF/GDNF) that regulate brain plasticity, an essential factor in schizophrenia.


Gut-Brain Axis and Schizophrenia

As research on the gut-brain axis and its impact on mental health continues to grow, studies may serve as potential indicators for the identification and prediction of schizophrenia. Furthermore, additional advances in this field may result in the development of innovative approaches targeting the gut microbiome in the treatment of schizophrenia. Despite the limitations, these findings open perspectives for future developments.


Studies in animal models also demonstrated that the transfer of feces from individuals with schizophrenia to mice affected neurotransmitter levels in the hippocampus, with a reduction in glutamate levels and an increase in glutamine and GABA

levels. These neurotransmitters play a crucial role in synaptic plasticity, and their dysfunction is associated with schizophrenia and other neurological disorders.


Although these findings suggest a promising connection between SCFAs, the gut microbiome, and schizophrenia, it is essential to recognize the current limitations of the research. The lack of large-scale human clinical trials and substantial variability in the composition of the gut microbiome and SCFA production among individuals make it challenging to establish a clear association with schizophrenia. Furthermore, the precise mechanism by which SCFAs influence schizophrenia remains unclear, requiring further research before considering therapeutic applications.


Given this, it is crucial to recognize the current limitations and the need for more research. As the scientific community deepens its study in this area, an enhanced understanding of the gut-brain axis in schizophrenia may offer valuable insights for diagnosis, treatment, and patient outcomes.


Clinical Practice

The findings related to the gut-brain axis in schizophrenia open new doors for approaching patients with this mental illness. Although it is important to emphasize that the research is in its early stages and that definitive therapies have not yet been established, mental health professionals should consider the health of the gut microbiome as a relevant factor in the assessment and treatment of patients with schizophrenia.

This may involve conducting more comprehensive assessments of the gut microbiome's state and targeted interventions, such as dietary modification, probiotics, and stress reduction, to promote a healthy balance in the microbiome. Individualization of treatment is critical, as the composition of the microbiome can vary significantly among patients. Additionally, more targeted therapies may become part of the treatment as research progresses.


Referências 

Assista o vídeo na Science Play com Roberta Carbonari: O impacto da alimentação na saúde mental

JU, Songhyun; SHIN, Yoonhwa; HAN, Sunhee; KWON, Juhui; CHOI, Tae Gyu; KANG, Insug; KIM, Sung Soo. The Gut–Brain Axis in Schizophrenia: the implications of the gut microbiome and sofa Production. Nutrients, [S.L.], v. 15, n. 20, p. 4391, 16 out. 2023. MDPI AG.

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