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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

Alignment of contig 44 to rRNA sequences. (A) BLAST alignment of contig 44 with Cordyceps gunnii 28S ribosomal RNA gene. (B) Section of multiple alignment between contig 44 and rRNA sequences from exemplar species in the orders Hypocreales or Malasseziales and human rRNA. (C) Phylogram illustrating the divergence between Hypocreales/contig 44, Malasseziales and human rRNA sequences.
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Fig7: Alignment of contig 44 to rRNA sequences. (A) BLAST alignment of contig 44 with Cordyceps gunnii 28S ribosomal RNA gene. (B) Section of multiple alignment between contig 44 and rRNA sequences from exemplar species in the orders Hypocreales or Malasseziales and human rRNA. (C) Phylogram illustrating the divergence between Hypocreales/contig 44, Malasseziales and human rRNA sequences.

Mentions: The contigs assigned to Hypocreales are extremely similar to the published sequences. For example, contig 44 has a similarity of 98.6% identity over 1162 nucleotides to Hypocreales Cordycipitaceae Cordyceps gunnii 28S ribosomal RNA (Figure 7A). This contig can also be aligned, with lower similarity, to rRNA from many other species. A region of contig 44 across which many orthologous sequences were available was selected and a multiple alignment made (Figure 7B). The phylogram derived from this alignment illustrates that contig 44 is considerably more similar to sequences from several species within Hypocreales than to those within Malasseziales and even more dissimilar to the human rRNA sequence (Figure 7C). Contigs generated from analysis of samples from the study by Wang et al.[25] were also similar to fungal sequences and indeed some were identical to contig 44 for >700 bp (Additional file5: Figure S3).Figure 7


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)

Alignment of contig 44 to rRNA sequences. (A) BLAST alignment of contig 44 with Cordyceps gunnii 28S ribosomal RNA gene. (B) Section of multiple alignment between contig 44 and rRNA sequences from exemplar species in the orders Hypocreales or Malasseziales and human rRNA. (C) Phylogram illustrating the divergence between Hypocreales/contig 44, Malasseziales and human rRNA sequences.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Fig7: Alignment of contig 44 to rRNA sequences. (A) BLAST alignment of contig 44 with Cordyceps gunnii 28S ribosomal RNA gene. (B) Section of multiple alignment between contig 44 and rRNA sequences from exemplar species in the orders Hypocreales or Malasseziales and human rRNA. (C) Phylogram illustrating the divergence between Hypocreales/contig 44, Malasseziales and human rRNA sequences.
Mentions: The contigs assigned to Hypocreales are extremely similar to the published sequences. For example, contig 44 has a similarity of 98.6% identity over 1162 nucleotides to Hypocreales Cordycipitaceae Cordyceps gunnii 28S ribosomal RNA (Figure 7A). This contig can also be aligned, with lower similarity, to rRNA from many other species. A region of contig 44 across which many orthologous sequences were available was selected and a multiple alignment made (Figure 7B). The phylogram derived from this alignment illustrates that contig 44 is considerably more similar to sequences from several species within Hypocreales than to those within Malasseziales and even more dissimilar to the human rRNA sequence (Figure 7C). Contigs generated from analysis of samples from the study by Wang et al.[25] were also similar to fungal sequences and indeed some were identical to contig 44 for >700 bp (Additional file5: Figure S3).Figure 7

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