Genomics of schizophrenia: time to consider the gut microbiome?

Abstract

Research into the genomics of schizophrenia promises much, but so far is resplendent with failures to replicate, and has yielded little of therapeutic potential. Within our bodies resides a dynamic population of gut microbes forming a symbiotic superorganism comprising a myriad of bacteria of approximately 10(14) cells, containing 100 times the number of genes of the human genome and weighing approximately the same as the human brain. Recent preclinical investigations indicate that these microbes majorly impact on cognitive function and fundamental behavior patterns, such as social interaction and stress management. We are pivotally dependent on the neuroactive substances produced by such bacteria. The biological diversity of this ecosystem is established in the initial months of life and is highly impacted upon by environmental factors. To date, this vast quantity of DNA has been largely ignored in schizophrenia research. Perhaps it is time to reconsider this omission.

Analysis of microbiota in first episode psychosis identifies preliminary associations with symptom severity and treatment response

“…Physical activity was assessed using the Gothenburg scale (Dinan et al, 2014). Based on these ratings, we created a dichotomous variable with "0" indicating all subjects who did not engage in physical activity during their leisure time and with "1" for physically active subjects.…”

“…Converging evidence suggests that gastrointestinal (GI) inflammation may have an important role in psychotic disorders (Dinan et al, 2014). Autoimmune diseases associated with chronic gastrointestinal inflammation, like celiac disease, Crohn's disease, and ulcerative colitis, are associated with increased risk of schizophrenia (Benros et al, 2011) and mood disorders (Benros et al, 2013).…”

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

“…125 In a mice model that shows behavioral changes that resemble schizophrenia, treatment with Bacteroides fragilis can ameliorate the symptoms. 126 However, a randomized clinical trial of a probiotic regimen containing Lactobacillus and Bifidobacterium strains failed to show any significant change in the psychiatric outcome measures was observed. 127 Another area in which information is rapidly evolving is that of autism spectrum disorders (ASD).…”

Envolvimento Da Flora Intestinal Na Modulação De Doenças Psiquiátricas

“…Os fatores etiológicos incluem o envolvimento de fatores genéticos e ambientais. Muitos pacientes esquizofrênicos também apresentam distúrbios gastrointestinais, evidenciando um possível envolvimento da composição da microbiota intestinal na patofisiologia da doença (146)(147)(148). Além disso, vários estudos têm demonstrado que o sistema imunológico está desregulado em pacientes esquizofrênicos, além de haver uma correlação entre o risco de desenvolver esquizofrenia e genes relacionados com o sistema imunológico (149)(150)(151)(152)(153), sugerindo uma possível modulação da flora intestinal.…”