Metatranscriptome analysis of blood in healthy individuals and irritable bowel syndrome patients

Abstract

Introduction. Although the presence of micro-organisms in the blood of healthy humans is a relatively new concept, there is a growing amount of evidence that blood might have its own microbiome. Gap Statement. Previous research has targeted the taxonomic composition of the blood microbiome using DNA-based sequencing methods, while little information is known about the presence of microbial transcripts obtained from the blood and their relation to conditions connected with increased gut permeability. Aim. To detect potentially alive and active micro-organisms and investigate differences in taxonomic composition between healthy people and patients with irritable bowel syndrome (IBS), we used the metatranscriptomics approach. Methodology. We collected blood samples from 23 IBS patients and 26 volunteers from the general population, and performed RNAseq on the isolated RNA. Reads corresponding to microbial genomes were identified with Kraken 2’s standard plus protozoa and fungi database, and re-estimated at genus level with Bracken 2.7. We looked for trends in the taxonomic composition, making a comparison between the IBS and control groups, accounting for other different factors. Results. The dominant genera in the blood microbiome were found to be Cutibacterium , Bradyrhizobium , Escherichia , Pseudomonas , Micrococcus , Delftia , Mediterraneibacter , Staphylococcus , Stutzerimonas and Ralstonia . Some of these are typical environmental bacteria and could partially represent contamination. However, analysis of sequences from the negative controls suggested that some genera which are characteristic of the gut microbiome ( Mediterraneibacter , Blautia , Collinsella , Klebsiella , Coprococcus , Dysosmobacter , Anaerostipes , Faecalibacterium , Dorea , Simiaoa , Bifidobacterium , Alistipes, Prevotella, Ruminococcus ) are less likely to be a result of contamination. Differential analysis of microbes between groups showed that some taxa associated with the gut microbiome ( Blautia , Faecalibacterium , Dorea , Bifidobacterium , Clostridium , Christensenella ) are more prevalent in IBS patients compared to the general population. No significant correlations with any other factors were identified. Conclusion. Our findings support the existence of the blood microbiome and suggest the gut and possibly the oral microbiome as its origin, while the skin microbiome is a possible but less certain source. The blood microbiome is likely influenced by states of increased gut permeability such as IBS.