Systemic Sclerosis Patients Have Deregulated Levels of Skin Microorganisms, Study Shows

Systemic Sclerosis Patients Have Deregulated Levels of Skin Microorganisms, Study Shows

Deregulation of the microorganisms that naturally populate the skin is associated with increased inflammation and disease duration in patients with systemic sclerosis, a study shows.

The study, “Microbiome dysbiosis is associated with disease duration and increased inflammatory gene expression in systemic sclerosis skin,” was published in the journal Arthritis Research & Therapy.

Bacteria take part in our lives more than we can imagine, and not just to cause diseases. There are several strains of bacteria that naturally live in our bodies and help us keep our system in balance. The most commonly known bacteria are those in the gut, which have a critical role in the digestive process and nutrient absorption. But many others are present in the body, including in our skin.

Studies have shown that deregulation of the natural body microbiome (communities of bacteria) can contribute to the development or progression of several diseases, including inflammatory disorders such as multiple sclerosis, psoriasis, and systemic sclerosis.

A team led by researchers at Geisel School of Medicine at Dartmouth further explored the relationship between skin bacterial load and the progression of systemic sclerosis.

Researchers examined skin biopsies collected from 23 patients with systemic sclerosis, including samples of damaged and non-damaged tissue from the forearm. Forearm skin biopsies were also obtained from six age- and gender-matched healthy volunteers for comparison.

Participants were recruited from three independent clinical centers, and they had clinically limited or diffuse systemic sclerosis. The study population also included patients with early disease (disease duration for less than 2.5 years) and very late-stage disease (disease duration for more than 8 years), to allow the analysis of microbiome changes through time.

Genetic analysis of skin samples revealed that several bacteria-related proteins were similar among samples, regardless of disease type or severity. In contrast, some proteins were more or less abundant compared to healthy controls, suggesting that the skin microbiome in systemic sclerosis patients may be changed.

A more detailed computer-based analysis revealed that patients had reduced amounts of lipophilic-subtype of bacteria, such as Propionibacterium and Staphylococcus, as well as increased levels of a wide range of gram-negative bacteria, including Burkholderia, Citrobacter, and Vibrio.

These microbiome differences were not associated with clinical disease subtype, with both limited and diffuse disease exhibiting broadly similar abundances of major bacteria groups. However, they found associations between disease duration and the levels of six of the top 21 microorganism groups.

The team also found lower amounts of the fungus Malassezia in the skin of patients, relative to controls, with the greatest decrease occurring in those with diffuse disease.

To further explore the role of the microbiome in systemic sclerosis skin lesions, the team performed an additional analysis focused on patient data alone. This approach revealed that the patients’ skin core microbiome was composed of 103 genera, and included representatives from bacteria, fungi, and viruses.

Once again, researchers could not find any major differences among patients with different disease subtypes. Still, microbiome profiles were strongly correlated with inflammatory status of the disease, suggesting a link between disease activity and microbial abundance.

In addition, the team found that the changes detected in skin microbiome were associated with significant alterations in the levels of pro-inflammatory genes.

“The data presented here demonstrate a possible mechanistic link between systemic sclerosis skin microbiome composition and disease pathology, with … a decrease in lipophilic taxa, and a shift to a largely gram-negative environment,” the researchers stated.

“Analysis of host-microbiome interactions, particularly with the host immune system, is necessary to determine the extent to which these organisms are capable of exacerbating and perpetuating the inflammatory responses in systemic sclerosis skin,” and shape disease-associated gene activity, they said.

Overall, the team concluded that “microbiome dysbiosis is associated with disease duration and increased inflammatory gene expression,” and suggests a “potential link between the skin microbiome and immune activation.”

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