The prenatal and early postnatal stages represent a critical time window for human brain development. Interestingly, this window partly overlaps with the maturation of the intestinal flora (microbiota) that play a critical role in the bidirectional communication between the central and the enteric nervous systems (microbiota-gut-brain axis). The microbial composition has important influences on general health and the development of several organ systems, such as the gastrointestinal tract, the immune system, and also the brain. Clinical studies have shown that microbiota alterations are associated with a wide range of neuropsychiatric disorders including autism spectrum disorder, attention deficit hyperactivity disorder, schizophrenia, and bipolar disorder. In this review, we dissect the link between these neuropsychiatric disorders and the intestinal microbiota by focusing on their effect on synaptic pruning, a vital process in the maturation and establishing efficient functioning of the brain. We discuss in detail how synaptic pruning is dysregulated differently in the aforementioned neuropsychiatric disorders and how it can be influenced by dysbiosis and/or changes in the intestinal microbiota composition. We also review that the improvement in the intestinal microbiota composition by a change in diet, probiotics, prebiotics, or fecal microbiota transplantation may play a role in improving neuropsychiatric functioning, which can be at least partly explained via the optimization of synaptic pruning and neuronal connections. Altogether, the demonstration of the microbiota's influence on brain function via microglial-induced synaptic pruning addresses the possibility that the manipulation of microbiota-immune crosstalk represents a promising strategy for treating neuropsychiatric disorders.

Purpose of review Schizophrenia (SCZ) 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 gut microbiome. Probiotics, defined as living microorganisms conferring health benefits to the host when administered in adequate amounts, seem to have supportive therapeutic effect in psychiatric disorders. The authors in this review provide an overview of this emerging research field and summarize both the publicated microbiome studies in SCZ and bipolar disorder and the current clinical research using probiotic supplementation in patients diagnosed with these disorders. Recent findingsThe current data indicate that there are differences in the microbiome in SCZ 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, no replicated findings so far. Probiotic supplementation was shown not only to alleviate gastrointestinal complaints but also reduce symptom severity, rehospitalization rates and cognitive improvement. Replication of improvement of cognition is needed. SummaryDifferences 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.

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