Effect of Dysbiosis in Gastrointestinal (GI) Tract on the Severity of Negative Symptoms in Schizophrenia: A Literature Review

Background: Schizophrenia is a complex neuropsychiatric disorder with positive symptoms (hallucination and delusional thoughts) and negative symptoms such as cognitive deficits, apathy and social withdrawals according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) and the International Classification of Diseases, 10th revision (ICD-10). Its specific etiology is still unclear but generally being attributed to the interaction between genetic and environmental factors which can effect as early as the gestational stage. Recent studies found increasing link between gastrointestinal (GI) microbiota and the gut-brain axis (GBA) to the early development of brain and onset of psychiatric disorders. There is a bidirectional communication between the central nervous system (CNS) and the peripheral gastrointestinal tract mediated by the GI microbiota via neural, hormonal and immunological pathways. Method: We searched the database of MEDLINE/PUBmed which consists more than 25 million references on biomedicine currently. MeSH terms such as “Brain-Gut-Axis”, “Dysbiosis”, “Negative Symptoms” and “Schizophrenia” were used. Boolean operator “AND” was used to join these MeSH terms to form a full search strategy. Studies linking dysbiosis of GI to negative symptoms of schizophrenia were included for this review while those elaborated on other psychiatric disorders and causes not linked to GI were excluded. Other database used includes Embase. Results: Studies showed microbiome of GI tract has an influence on the central Brain-Derived Neurotropic Factor (BDNF) level and the maintenance of N-methyl-D-aspartate (NMDAR) production. Both were found to play a role in cognitive function and synaptic plasticity and were linked to development of schizophrenia and other neurodegenerative disorders such as depression and dementias. In the absence of GI microbes, central BDNF level was reduced. Such reduction led to decreased NMDAR input onto GABA inhibitory interneurons, resulted in disruption of signal-to-noise ratio with consequence of aberrant synaptic behaviour and cognitive deficits. Conclusions: Dysbiosis of GI tract plays a role in the etiology of Schizophrenia and has an impact on the severity of its negative symptoms.