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Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma.

Beatty M, Guduric-Fuchs J, Brown E, Bridgett S, Chakravarthy U, Hogg RE, Simpson DA - BMC Genomics (2014)

Bottom Line: The human microbiome plays a significant role in maintaining normal physiology.The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status.The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.

View Article: PubMed Central - PubMed

Affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK. David.Simpson@qub.ac.uk.

ABSTRACT

Background: The human microbiome plays a significant role in maintaining normal physiology. Changes in its composition have been associated with bowel disease, metabolic disorders and atherosclerosis. Sequences of microbial origin have been observed within small RNA sequencing data obtained from blood samples. The aim of this study was to characterise the microbiome from which these sequences are derived.

Results: Abundant non-human small RNA sequences were identified in plasma and plasma exosomal samples. Assembly of these short sequences into longer contigs was the pivotal novel step in ascertaining their origin by BLAST searches. Most reads mapped to rRNA sequences. The taxonomic profiles of the microbes detected were very consistent between individuals but distinct from microbiomes reported at other sites. The majority of bacterial reads were from the phylum Proteobacteria, whilst for 5 of 6 individuals over 90% of the more abundant fungal reads were from the phylum Ascomycota; of these over 90% were from the order Hypocreales. Many contigs were from plants, presumably of dietary origin. In addition, extremely abundant small RNAs derived from human Y RNAs were detected.

Conclusions: A characteristic profile of a subset of the human microbiome can be obtained by sequencing small RNAs present in the blood. The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status. The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.

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Related in: MedlinePlus

Taxonomic profile and relative expression between individuals of abundant contigs. (A) The top 20 contigs ranked according to the total number of reads aligned to them from all samples. All the contigs matched rRNA and the top BLAST hit is shown. The lowest common taxonomic rank was assigned by analysis of the BLAST hits with scores within 5% of the top hit. The proportion of reads mapping to each contig in individuals and overall is indicated. (B) Phylogenetic tree of the top 20 contigs generated with MEGAN. The number of contigs assigned at each node is indicated.
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Fig6: Taxonomic profile and relative expression between individuals of abundant contigs. (A) The top 20 contigs ranked according to the total number of reads aligned to them from all samples. All the contigs matched rRNA and the top BLAST hit is shown. The lowest common taxonomic rank was assigned by analysis of the BLAST hits with scores within 5% of the top hit. The proportion of reads mapping to each contig in individuals and overall is indicated. (B) Phylogenetic tree of the top 20 contigs generated with MEGAN. The number of contigs assigned at each node is indicated.

Mentions: For the 20 exogenous contigs represented by the most reads, the top 5% of BLAST hits (min score 50) were analysed with the MEGAN taxonomic classification tool[32, 33]. They all mapped to rRNA, 16 of the 20 to fungal sequences, with the lowest common taxonomic rank for 5 of the top 6 being the fungal order Hypocreales or lower (FigureĀ 6). The relative abundances of contigs across the samples were very consistent. Contig 44, which mapped to Hypocreales rRNA, was the most abundant in 5 of the 6 individuals. Notably 9 of the top BLAST hits for the 20 contigs were to the genus Fusarium. The mycoprotein Quorn is derived from Fusarium venenatum[34]. Although it is intriguing to speculate that the sequences we observe are derived from Quorn, it seems unlikely that all 6 subjects would have had this in their diet. In addition, although several contigs align very closely with published F. venenatum rRNA sequences, they match even more closely to other species (Additional file4: Figure S2).Figure 6


Small RNAs from plants, bacteria and fungi within the order Hypocreales are ubiquitous in human plasma.

Beatty M, Guduric-Fuchs J, Brown E, Bridgett S, Chakravarthy U, Hogg RE, Simpson DA - BMC Genomics (2014)

Taxonomic profile and relative expression between individuals of abundant contigs. (A) The top 20 contigs ranked according to the total number of reads aligned to them from all samples. All the contigs matched rRNA and the top BLAST hit is shown. The lowest common taxonomic rank was assigned by analysis of the BLAST hits with scores within 5% of the top hit. The proportion of reads mapping to each contig in individuals and overall is indicated. (B) Phylogenetic tree of the top 20 contigs generated with MEGAN. The number of contigs assigned at each node is indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230795&req=5

Fig6: Taxonomic profile and relative expression between individuals of abundant contigs. (A) The top 20 contigs ranked according to the total number of reads aligned to them from all samples. All the contigs matched rRNA and the top BLAST hit is shown. The lowest common taxonomic rank was assigned by analysis of the BLAST hits with scores within 5% of the top hit. The proportion of reads mapping to each contig in individuals and overall is indicated. (B) Phylogenetic tree of the top 20 contigs generated with MEGAN. The number of contigs assigned at each node is indicated.
Mentions: For the 20 exogenous contigs represented by the most reads, the top 5% of BLAST hits (min score 50) were analysed with the MEGAN taxonomic classification tool[32, 33]. They all mapped to rRNA, 16 of the 20 to fungal sequences, with the lowest common taxonomic rank for 5 of the top 6 being the fungal order Hypocreales or lower (FigureĀ 6). The relative abundances of contigs across the samples were very consistent. Contig 44, which mapped to Hypocreales rRNA, was the most abundant in 5 of the 6 individuals. Notably 9 of the top BLAST hits for the 20 contigs were to the genus Fusarium. The mycoprotein Quorn is derived from Fusarium venenatum[34]. Although it is intriguing to speculate that the sequences we observe are derived from Quorn, it seems unlikely that all 6 subjects would have had this in their diet. In addition, although several contigs align very closely with published F. venenatum rRNA sequences, they match even more closely to other species (Additional file4: Figure S2).Figure 6

Bottom Line: The human microbiome plays a significant role in maintaining normal physiology.The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status.The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.

View Article: PubMed Central - PubMed

Affiliation: Centre for Experimental Medicine, Queen's University Belfast, Belfast, Northern Ireland, UK. David.Simpson@qub.ac.uk.

ABSTRACT

Background: The human microbiome plays a significant role in maintaining normal physiology. Changes in its composition have been associated with bowel disease, metabolic disorders and atherosclerosis. Sequences of microbial origin have been observed within small RNA sequencing data obtained from blood samples. The aim of this study was to characterise the microbiome from which these sequences are derived.

Results: Abundant non-human small RNA sequences were identified in plasma and plasma exosomal samples. Assembly of these short sequences into longer contigs was the pivotal novel step in ascertaining their origin by BLAST searches. Most reads mapped to rRNA sequences. The taxonomic profiles of the microbes detected were very consistent between individuals but distinct from microbiomes reported at other sites. The majority of bacterial reads were from the phylum Proteobacteria, whilst for 5 of 6 individuals over 90% of the more abundant fungal reads were from the phylum Ascomycota; of these over 90% were from the order Hypocreales. Many contigs were from plants, presumably of dietary origin. In addition, extremely abundant small RNAs derived from human Y RNAs were detected.

Conclusions: A characteristic profile of a subset of the human microbiome can be obtained by sequencing small RNAs present in the blood. The source and functions of these molecules remain to be determined, but the specific profiles are likely to reflect health status. The potential to provide biomarkers of diet and for the diagnosis and prognosis of human disease is immense.

Show MeSH
Related in: MedlinePlus