Transcriptome analysis in whole blood reveals increased microbial diversity in schizophrenia

Abstract

The role of the human microbiome in health and disease is increasingly appreciated. We studied the composition of microbial communities present in blood across 192 individuals, including healthy controls and patients with three disorders affecting the brain: schizophrenia, amyotrophic lateral sclerosis, and bipolar disorder. By using high-quality unmapped RNA sequencing reads as candidate microbial reads, we performed profiling of microbial transcripts detected in whole blood. We were able to detect a wide range of bacterial and archaeal phyla in blood. Interestingly, we observed an increased microbial diversity in schizophrenia patients compared to the three other groups. We replicated this finding in an independent schizophrenia case–control cohort. This increased diversity is inversely correlated with estimated cell abundance of a subpopulation of CD8+ memory T cells in healthy controls, supporting a link between microbial products found in blood, immunity and schizophrenia.

Identification of gut microbiome markers for schizophrenia delineates a potential role of Streptococcus

“…Surprisingly, gut microbiota diversities based on genus level taxonomy and annotated genes were higher in schizophrenic patients compared to controls. In accordance with our data, both α diversity and β diversity showed an increase in the blood microbiota of schizophrenic patients 37 . The microbes in blood are thought to originate from the gut as well as from the oral cavities 38,39 .…”

“…The microbes in blood are thought to originate from the gut as well as from the oral cavities 38,39 . Moreover, the increased diversity of the blood microbiota may be due to the nonspecific overall increased microbial burden in schizophrenia 37 , which is supported by our observed increased microbial gene number in patients’ gut. The considerable heterogeneity of the etiology and clinical manifestation of schizophrenia 40,41 may be implicated in such an increase in the microbiota diversity.…”

Multi-Method Characterisation of the Human Circulating Microbiome

“…We support this explanation for the detection of viable bacteria within the bloodstream of healthy individuals, however, suggest that this phenomenon does not adequately explain the existence of the blood microbiome ( the presence of bacteria-derived nucleic acids ) when one considers the number of studies that demonstrate significant and apparently disease-specific differences in the composition of the blood microbiome. Moreover, examination of the bacterial taxa reported in these studies reveal similar blood microbiota compositions across the different studies, whereby Proteobacteria dominate (relative abundance values typically ranging from 85%-90%), and Firmicutes, Actinobacteria, and Bacteroidetes present to a lesser extent 2,7,25,28 . This suggests the existence of a core blood microbiome profile that persists independent of study environment or analytical methodology.…”

The mutual interplay of gut microbiota, diet and human disease

“…The stability of the gut microbiota has been associated with neuropsychiatric diseases. It is worth mentioning that also blood circulating microbiota have been suggested to play a role in neuropsychiatric disorders [153]. In a study on major depressive disorder, faecal samples from affected patients displayed increased Bacteroidetes, Proteobacteria and Actinobacteria, whereas Firmicutes levels were significantly reduced compared to age-matched controls, and these alterations positively correlated with the severity of depressive symptoms [154].…”