How Bacterial DNA in Blood Could Revolutionize Lupus Treatment
Imagine if your blood contained messages from throughout your body—tiny molecular bottles carrying news about your health. This isn't science fiction; it's the cutting edge of lupus research.
Plasma microbial cell-free DNA (mcfDNA) are fragments of DNA from bacteria, fungi, and other microbes circulating in our bloodstream.
These microbial messages may hold crucial information about what triggers lupus flares and drives disease activity 1 .
Scientists have discovered that fragments of DNA from bacteria, fungi, and other microbes circulate in our bloodstream, potentially holding crucial information about what triggers lupus flares and drives disease activity.
DNA from microorganisms living in or on our bodies—bacteria, viruses, and fungi that release DNA fragments into the bloodstream 1 .
When the delicate balance of our microbiome is disrupted, potentially triggering or worsening autoimmune conditions 1 .
Systemic lupus erythematosus is a chronic autoimmune disease notorious for its complexity and variability. In lupus, the immune system mistakenly attacks the body's own tissues, causing widespread inflammation and damage to joints, skin, kidneys, heart, and other organs 3 .
In May 2025, a team of researchers published a groundbreaking preliminary study that directly explored the relationship between plasma mcfDNA and disease activity in lupus patients 1 .
54 patients with SLE and 36 healthy controls, divided into three distinct groups based on disease status.
Blood samples collected using K2-EDTA tubes to prevent clotting and preserve fragile DNA fragments.
Karius Discovery assay sequenced DNA at 400 million paired-end reads per sample.
Rigorous analytical filters and machine learning classifiers applied to identify microbial signatures.
| Body Site Origin | Representative Microbial Species Detected |
|---|---|
| Oral Microbiome | Streptococcus, Prevotella, Porphyromonas, Veillonella |
| Gastrointestinal Microbiome | Bacteroides, Alcaligenes, Streptomyces, Campylobacter |
| Skin Microbiome | Staphylococcus, Corynebacterium, Acinetobacter |
| Characteristic | Lupus Patients | Healthy Controls |
|---|---|---|
| Number of Participants | 54 | 36 |
| Median Age | 37.5 years | 45 years |
| Female Percentage | 85% | 61% |
| History of Lupus Nephritis | 46% | Not applicable |
| Key Finding: Elevated mcfDNA | Yes, from oral, GI, and skin microbes | No significant elevations |
| Key Finding: Machine Learning Classification | Possible distinction between disease states | N/A |
| Tool or Method | Primary Function | Application in mcfDNA Research |
|---|---|---|
| K2-EDTA Blood Collection Tubes | Prevents blood clotting and preserves cell-free DNA | Maintains integrity of fragile mcfDNA fragments between collection and processing |
| Next-Generation Sequencing (NGS) | Determines precise order of nucleotides in DNA fragments | Identifies microbial species by matching sequences to known microbial genomes |
| Droplet Digital PCR (ddPCR) | Precisely quantifies DNA molecules | Provides absolute count of mcfDNA molecules; offers high sensitivity for low-abundance targets 7 |
| Bioinformatics Filters | Distinguishes true signals from contamination | Removes background noise to reveal biologically relevant microbial signatures |
| Machine Learning Algorithms | Identifies patterns in complex datasets | Finds microbial signatures that distinguish disease states from healthy controls |
McfDNA could provide a much-needed additional biomarker that offers a different perspective on disease activity 3 .
If specific mcfDNA signatures precede clinical flares, regular blood tests could provide early warning 8 .
Profiling individual microbial signatures might help tailor treatments to specific patients 1 .
The study included 54 lupus patients—a good start but insufficient for drawing broad conclusions. Future research needs to include hundreds or even thousands of patients.
Studies that track mcfDNA levels in the same patients over time, through flares and remissions, will be essential.
A crucial unanswered question is whether the elevated mcfDNA is merely a bystander effect or actively contributes to disease pathogenesis 1 .
The discovery that microbial cell-free DNA in plasma correlates with lupus disease activity represents more than just another potential biomarker—it signifies a fundamental shift in how we conceptualize the relationship between our bodies, our microscopic inhabitants, and autoimmune disease.
"Our pilot study provides preliminary data suggesting an increase in mcfDNA concentration from signature microbial species that can distinguish patients with SLE from controls and differentiate between disease subgroups" 1 .
As research progresses, checking the microbial forecast in a lupus patient's blood might become as routine as checking antibodies is today—a powerful tool in the ongoing effort to tame this complex autoimmune disease.