Table 1.
Summary of different human blood microbiota studies conducted on healthy or diseased individuals.
| Study Population | Health Indications | Sample | Methodology | Findings | Ref. |
|---|---|---|---|---|---|
| Healthy individuals | |||||
| A total of 100 men and women were chosen at random. | Only healthy individuals were selected | RBCs | Radioactive uptake of nucleosides and amino acids by RBCs | Finding of L-phase bacterial forms in the healthy blood | (Tedeschi et al., 1969) |
| 4 healthy individuals | Healthy individuals only | Whole blood | qPCR and rRNA gene-specific fluorescent probes targeting the conserved region of 16S rDNA | Bacteria from five divisions and seven distinct phylogenetic groups detected in the blood | (Nikkari et al., 2001) |
| 25 healthy individuals. | Healthy individuals only | Whole blood | Characterization by 16S rRNA and gyrB genes and detected by dark-field microscopy and fluorescent in situ hybridization (FISH) | Pleomorphic antibiotic susceptible bacteria existing in healthy blood with limited growth (possibly Pseudomonas) | (Mclaughlin et al., 2002) |
| 2 healthy individuals | Healthy individuals only | Whole blood | 16S rRNA PCR and Sanger sequencing | Aquabacterium, Budvicia, Stenotrophomonas, Serratia, Bacillus, and Flavobacteria identified only in clones | (Moriyama et al., 2008) |
| 60 self-reported healthy individuals’ ≥49 years. | Almost 64% were positive for bacterial growth | Blood plasma and RBC suspension | Blood suspensions incubated on TSA or blue lactose plates, and 16S rRNA gene colony PCR used to identify bacteria | Bacterial growth observed in 35% of RBC fractions and 53% of plasma fractions. Staphylococci, Propionibacterium, Micrococcus, and Bacillus most frequently found | (Damgaard et al., 2015) |
| 30 healthy blood donors (18 to 53 years old). | Healthy blood donors | Blood fractions (buffy coat, plasma, and RBCs) | 16S rRNA gene qPCR and 16S targeted metagenomic sequencing (Illumina MiSeq) | Buffy coat, erythrocytes, and plasma were positive for bacterial DNA. Most prevalent bacterial DNA belong to Proteobacteria and Actinobacteria (Firmicutes and Bacteroidetes also found) | (Païssé et al., 2016) |
| 28 blood samples from healthy individuals | Healthy individuals only | Whole blood, positive for bacterial cultures | 16S rRNA genes and ITS2 targeted sequencing on Illumina MiSeq and TEM | Cultural and molecular characterization of healthy blood microbiota (Proteobacteria and Basidiomycota were prominent) | (Panaiotov et al., 2018) |
| Diabetic vs. healthy individuals | |||||
| 119 diabetic and 480 non-diabetic patients | Diabetic and non-diabetic individuals | Whole blood | Aerobic and anaerobic blood cultures | Diabetes patients have higher Klebsiella and Staphylococci | (Leibovici et al., 1991) |
| 3,280 people without diabetes and obesity at baseline (9 years observation) | Non-diabetic patients with bacterial DNA in their blood | DNA extracted from leukocytes (peripheral blood) | 16S rDNA quantitative PCR and pooled pyrosequencing | Regardless of any risk factors, individuals with high 16S rDNA levels developed diabetes. High prevalence of Ralstonia spp. in individuals who developed diabetes | (Amar et al., 2011) |
| 50 diabetic and 50 non-diabetic individuals | Type 2 diabetes patients and control individuals | Circulating RNA isolated from blood plasma | Measurement of 16S rDNA and genus-specific 16S rDNA by qRT-PCR | High 16S bacterial rRNA content in diabetes patients; Clostridium coccoides and the Atopobidum cluster were particularly abundant | (Sato et al., 2014) |
| 50 diabetic and 100 non-diabetic Individuals | Diabetic and healthy individuals selected by pre-diagnostic analysis | Circulating DNA isolated from blood plasma | 16S rRNA amplicon sequencing by Illumina MiSeq | Bacteroides spp. showed an inverse correlation and Sediminibacterium spp. showed a positive correlation with diabetes | (Qiu et al., 2019) |
| 30 healthy people, 30 type 2 diabetes, and 30 pre-diabetic people | Pre-diabetic and healthy individuals | Buffy coat | Real-time PCR using genus-specific 16s rRNA primers | Akkermansia and Faecalibacterium were higher in healthy individuals compared to pre-diabetic and type 2 diabetes | (Ghaemi et al., 2021) |
| 1,285 RASIG individuals under MARK-AGE an EU project (2008-2012). | Seropositive individuals for HCV, HIV, cancer | DNA extracted from whole blood | Quantification of 16S rRNA by real-time qPCR | High level of bacterial DNA was associated with higher level of insulin and glucose | (D’aquila et al., 2021) |
| Cardiovascular vs. healthy individuals | |||||
| 1,312 incident coronary heart disease patients and 727 incident stroke patients | Patients with cardiovascular problems | DNA extracted from peripheral blood leukocytes | Analysis of Atherosclerosis Risk Communities study (ARIC) results over the period 1987–2017 | Inpatient and outpatient infections are associated with CVD risk | (Cowan et al., 2018) |
| 3,936 people without diabetes or obesity at baseline | Bacterial DNA in blood of individuals not presenting CVD. | DNA extracted from leukocytes (peripheral blood) | Measurement of Eubacteria and Proteobacteria 16S rDNA by qPCR | There was a positive correlation of Proteobacteria, and inverse correlation of Eubacteria, with cardiovascular events | (Amar et al., 2013) |
| 31 CVD patients and 10 healthy controls | CVD and healthy individuals with no history of antibiotics (30 days) | DNA extracted from whole blood | Amplicon sequencing of 16S rDNA (Ion Torrent PGM) | Increase in Pseudomonadaceae and decrease in Gammaproteobacteria, Bacillales, and Staphylococcaceae in CVD patients | (Rajendhran et al., 2013) |
| 80 CVD patients and 40 healthy blood donors | Healthy individuals have bacterial DNA in their plasma | Circulating DNA isolated from blood plasma | Measurement of total 16S rDNA and β-globin gene concentrations by qRT-PCR. Shotgun sequencing of DNA and amplicon sequencing of 16S rDNA (Ion Torrent PGM) | The 16S rRNA/β-globin gene ratio was higher in CVD patients than in controls. Actinobacteria and Bacteriophages were dominant in CVD patients whereas Proteobacteria and eukaryotic viruses were dominant in controls | (Dinakaran et al., 2014) |
| Miscellaneous | |||||
| 23 healthy individuals and 62 patients with sepsis | All were positive for bacterial DNA | Whole blood | 16S rRNA gene targeted metagenomic NGS | Healthy samples presented higher diversity than sepsis patients. Proteobacteria were lower in healthy individuals, while Actinobacteria decreased in sepsis patients | (Gosiewski et al., 2017) |
| 9 cirrhotic and nine healthy individuals (≥60 years) | Bacteria found in two healthy individuals | Blood (plasma) | 16SrRNA target gene qPCR | Bacterial biodiversity and amount of bacterial DNA increased in cirrhotic patients | (Traykova et al., 2017) |
| 50 patients with severe acute pancreatitis and 12 healthy individuals | Bacterial DNA present in all healthy participants | DNA from whole blood and neutrophils | 16S rDNA gene qPCR and targeted metagenomic sequencing using Ion Torrent. | 16S rDNA gene copies were higher in patients. Healthy phyla include Proteobacteria, Actinobacteria, Firmicutes and Bacteroidetes. Bacteroidetes were high and Actinobacteria lower in patients | (Li et al., 2018) |
| 192 individuals (48 with schizophrenia, 47 with lateral sclerosis, 48 with bipolar disorder and 49 healthy). | Bacterial DNA present healthy individual’s blood | Whole blood | High-quality unmapped RNA sequencing | The most prevalent phyla among the groups were Proteobacteria, Firmicutes, and Cyanobacteria, and schizophrenia patients have high microbial diversity. | (Olde Loohuis et al., 2018) |
| Healthy and asthma patients (five each, all women) | Bacterial transcripts in blood of all healthy individuals | Plasma fractions | 16S rRNA gene sequencing. De novo assembly of unmapped mRNA reads, and culturing | Most abundant phyla were Proteobacteria, Actinobacteria, Firmicutes, and Bacteroidetes | (Whittle et al., 2019) |