Gut Microbiome in Patients with Schizophrenia and Bipolar Disorder

Schizophrenia and bipolar disorder are severe mental disorders, both placing a significant burden on individuals’ wellbeing and global health generally. The complex interaction of multiple mechanisms, underlying these disorders, still needs further elucidation. Increased activation of components of the immune system may be involved, including alterations in intestinal permeability and the gut microbiome. Probiotics, defined as living microorganisms conferring health benefits to the host when administered in adequate amounts, may have some supportive therapeutic effect in psychiatric disorders. The authors in this chapter provide an overview of this emerging research field and summarize both the published microbiome studies in schizophrenia and bipolar disorder and the current clinical research using probiotic supplementation in patients diagnosed with these disorders. The current data indicate that there are differences in the microbiome in schizophrenia and bipolar disorder patients as compared with healthy controls. Part of these differences may be induced by medication use, others by smoking and other lifestyle factors. Correlations between microbiome quantification and symptom severity have been observed in cross-sectional studies, but unfortunately, there are nor replicated findings so far. Probiotic supplementation was shown not only to alleviate gastrointestinal complaints but also reduce symptom severity, rehospitalization rates, and cognitive improvement in some studies. Replication of improvement of cognition is needed. In conclusion, differences in microbiome have been shown in both SCZ and bipolar disorder in comparison to healthy controls. Evidence that probiotics can improve psychiatric functioning is still very limited.</p

Role of the gut microbiome in three major psychiatric disorders

Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia-spectrum disorders (SSD) are heterogeneous psychiatric disorders, which place significant burden on patient's well-being and global health. Disruptions in the gut-microbiome may play a role in these psychiatric disorders. This review presents current data on composition of the human gastrointestinal microbiota, and its interaction mechanisms in the gut-brain axis in MDD, BD and SSD. Diversity metrics and microbial relative abundance differed across studies. More studies reported inconsistent findings (n = 7) or no differences (n = 8) than studies who reported lower α-diversity in these psychiatric disorders (n = 5). The most consistent findings across studies were higher relative abundances of the genera Streptococcus, Lactobacillus, and Eggerthella and lower relative abundance of the butyrate producing Faecalibacterium in patients with psychiatric disorders. All three increased genera were associated with higher symptom severity. Confounders, such as medication use and life style have not been accounted for. So far, the results of probiotics trials have been inconsistent. Most traditional and widely used probiotics (consisting of Bifidobacterium spp. and Lactobacillus spp.) are safe, however, they do not correct potential microbiota disbalances in these disorders. Findings on prebiotics and faecal microbiota transplantation (FMT) are too limited to draw definitive conclusions. Disease-specific pro/prebiotic treatment or even FMT could be auspicious interventions for prevention and therapy for psychiatric disorders and should be investigated in future trials

Higher T central and lower effector memory cells in bipolar disorder:A differentiation abnormality?

The aim of this study was to elucidate the nature of T cell abnormalities in bipolar disorder (BD). With the use of multicolor flow cytometry, we first quantified the composition of the different memory and pro-inflammatory immune subpopulations in samples of 58 patients with BD and compared them to 113 healthy controls. Second, to assess if cytomegalovirus infection was related to the resulted immune subpopulation compositions in the two groups, we measured cytomegalovirus-specific antibodies in serum. Thirdly, we assessed differences between the two groups in the serum levels of the immune cell differentiation factor interleukin-7. Compared to healthy controls, patients showed significantly higher T helper-17, T regulatory and T central memory cells (CD4+ and CD8+). Besides, patients showed significantly lower CD4+ T effector memory and CD4+ T effector memory re-expressing RA cells. Cytomegalovirus infection was not related to the observed abnormalities, with the exception of T helper-17 cells. This immune subpopulation was significantly higher only in patients seropositive to cytomegalovirus infection. Finally, interleukin-7 levels were significantly lower in BD compared to healthy controls. In conclusion, the aberrant levels of T memory cell populations in BD may suggest a T cell differentiation abnormality. The role of interleukin-7 in this putative abnormality should be further investigated.</p

Higher T central and lower effector memory cells in bipolar disorder:A differentiation abnormality?

The aim of this study was to elucidate the nature of T cell abnormalities in bipolar disorder (BD). With the use of multicolor flow cytometry, we first quantified the composition of the different memory and pro-inflammatory immune subpopulations in samples of 58 patients with BD and compared them to 113 healthy controls. Second, to assess if cytomegalovirus infection was related to the resulted immune subpopulation compositions in the two groups, we measured cytomegalovirus-specific antibodies in serum. Thirdly, we assessed differences between the two groups in the serum levels of the immune cell differentiation factor interleukin-7. Compared to healthy controls, patients showed significantly higher T helper-17, T regulatory and T central memory cells (CD4+ and CD8+). Besides, patients showed significantly lower CD4+ T effector memory and CD4+ T effector memory re-expressing RA cells. Cytomegalovirus infection was not related to the observed abnormalities, with the exception of T helper-17 cells. This immune subpopulation was significantly higher only in patients seropositive to cytomegalovirus infection. Finally, interleukin-7 levels were significantly lower in BD compared to healthy controls. In conclusion, the aberrant levels of T memory cell populations in BD may suggest a T cell differentiation abnormality. The role of interleukin-7 in this putative abnormality should be further investigated.</p

Association between gut permeability, brain volume, and cognition in healthy participants and patients with schizophrenia spectrum disorder

INTRODUCTION: The barrier function of the gut is important for many organs and systems, including the brain. If gut permeability increases, bacterial fragments may enter the circulation, giving rise to increased systemic inflammation. Increases in bacterial translocation are reflected in higher values of blood markers, including lipopolysaccharide binding protein (LBP) and soluble cluster of differentiation 14 (sCD14). Some pioneer studies showed a negative association between bacterial translocation markers and brain volumes, but this association remains scarcely investigated. We investigate the effect of bacterial translocation on brain volumes and cognition in both healthy controls and patients with a schizophrenia spectrum disorder (SSD).MATERIALS AND METHODS: Healthy controls (n = 39) and SSD patients (n = 72) underwent an MRI-scan, venipuncture and cognition assessments. We investigated associations between LBP and sCD14 and brain volumes (intracranial volume, total brain volume, and hippocampal volume) using linear regression. We then associated LBP and sCD14 to cognitive function using a mediation analysis, with intracranial volume as mediator.RESULTS: Healthy controls showed a negative association between hippocampal volume and LBP (b = -0.11, p = .04), and intracranial volume and sCD14 (b = -0.25, p = .07). Both markers were indirectly associated with lower cognitive functioning in healthy controls (LBP: b = -0.071, p = .028; sCD14: b = -0.213, p = .052), mediated by low intracranial volume. In the SSD patients, these associations were markedly less present.CONCLUSION: These findings extend earlier studies suggesting that increased bacterial translocation may negatively affect brain volume, which indirectly impacts cognition, even in this young healthy group. If replicated, this finding stresses the importance of a healthy gut for the development and optimal functioning of the brain. Absence of these associations in the SSD group may indicate that other factors such as allostatic load, chronic medication use and interrupted educational carrier had larger impact and attenuated the relative contribution of bacterial translocation.</p

Metabolic phenotyping reveals a potential link between elevated faecal amino acids, diet and symptom severity in individuals with severe mental illness

The brain-gut axis is increasingly recognized as an important contributing factor in the onset and progression of severe mental illnesses such as schizophrenia spectrum disorders and bipolar disorder. This study investigates associations between levels of faecal metabolites identified using 1H-NMR, clinical parameters, and dietary components of forty-two individuals diagnosed in a transdiagnostic approach to have severe mental illness. Faecal levels of the amino acids; alanine, leucine, and valine showed a significant positive correlation with psychiatric symptom severity as well as with dairy intake. Overall, this study proposes a diet-induced link between the brain-gut axis and the severity of psychiatric symptoms, which could be valuable in the design of novel dietary or therapeutic interventions to improve psychiatric symptoms