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Is the healthy human blood microbiome a contamination or something else?

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J
Juran Nov 28, 2020
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Necessity

Is the problem still unsolved?

Conciseness

Is it concisely described?

Could microbes be found in the blood of a healthy individual?
Is it sample contamination or maybe a sign of an ongoing infection?
Where do they come from?

Introduction


Since microbes play a giant role in and outside of our bodies, they were throughoutly researched in the last decade by more than 2000 scientists, in the comprehensive study called human microbiome research. Although the primary field of research was the human intestine microbiome, it soon covered the microbial populations of other tissues, such as mouth, skin, vagina, placenta, urogenital tract, etc. Latest findings open an often criticized field of research – the human blood microbiome . Wait, what? Microbes in blood?

For ages, it was believed that the blood, as the main transport system of the body, is constituted solely of the blood cells, platelets, and plasma. It was supposed to be sterile, because white blood cells, the body's highly efficient monitoring system, should detect and help to remove the invaders. Therefore, any microbial trait found circulating was a sign of an ongoing or developing disease . How is then possible that more and more papers are supporting the microbial presence in the blood of healthy persons?

Pieces of evidence


The first pieces of evidence of microbes in the blood of healthy individuals were reported in 1969, and later in 1977, and were based on higher presence of nucleosides and amino acids in erythrocyte suspensions or culturing after lysis and filtration. The following studies used more sophisticated techniques like qPCR, TEM and dark-field microscopy, FISH, and similar. Pieces of evidence collected this way were easily diminished by different theories and were not solid ground for further research .

With the increasing development of next-generation sequencing, robust and reliable pieces of evidence, based on 16S rDNA, started to occur and bacterial transcripts were detected and confirmed in healthy individuals. The results stated that the human blood microbiome is mainly composed of Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes, but varies between studies .

What could it be and how did it enter the bloodstream?


Up to date, a few reasonable theories explaining what could it be persisted:

  1. They are the real active microbes, which are:
  2. the result of external contamination (probably from reagents and lab surfaces/air). It is true that many controls were not included in the vast of human microbiome experiments and that many negative controls yielded a huge amount of DNA sequence reads . On the other hand, the analyses of the negative controls showed significantly less or complete absence of the 16S rRNA amplification. Even if the control yielded DNA reads, they were significantly different from the diseases or healthy blood samples .
  3. the consequence of the recent "accidental" diffusion of the microbes from the skin, intestine, or the mouth, through the membranes of the epithelium (especially when in the disrupted/ compromised state); should not be present in the next sample (few days/months later) because detected and removed by the immune system
  4. the sign of an active "silent" infection?
  5. the normal thing in every blood?
2. They are the real inactive or dormant microbes
They entered the bloodstream by early colonization of the fetal circulatory system before the delivery (in utero) or by the diffusion of the microbes from the skin, intestine, or the mouth and somehow stayed present in the blood. How?
Some pieces of evidence explain that the microbes can survive in the erythrocytes or lymphocytes for a long time and avoid immunosurveillance.


What do you think?
Can it just be a coincidence?
Is there a valid explanation or an example that supports any of the theories?

[1]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519389/#B95

[2]https://pubmed.ncbi.nlm.nih.gov/25133738/

[3]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6519389/#B66

[4]https://pubmed.ncbi.nlm.nih.gov/29743478/

[5]https://pubmed.ncbi.nlm.nih.gov/18667036/

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