The Surprising Trigger of Diabetes: Staph Overgrowth on Your Skin

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"We basically reproduced Type 2 diabetes in rabbits simply through chronic exposure to the staph superantigen,” Patrick Schlievert, Professor of Microbiology and Immunology at the University of Iowa, United States, said in response to findings from his lab at the time.

The Diabetic Rabbits

It started in 2015 when Schlievert’s team purified the superantigen of the common skin bacterium, Staphylococcus aureus, called the toxic shock syndrome toxin-1 (TSST-1). Antigens are simply foreign substances that provoke an immune response from the immune system.

This Staph Superantigen is known to cause lethal infections — such as toxic shock syndrome, sepsis, and endocarditis (inflammation of the heart’s inner linings)— if it breaches the skin layer and enters the bloodstream in high amounts.

They then introduced this Staph superantigen into an open wound on the rabbits’ skin. Soon the rabbits developed systemic inflammation, increased blood levels of endotoxin, insulin resistance, and glucose intolerance. They had just made the rabbits diabetic from exposure to Staph superantigen.

“We worked with rabbits because their response to staph superantigens is similar to humans’,” Schlievert explained. “We feel we can say it’s a cause of type 2 diabetes in people.”

Further investigations revealed that the Staph superantigen, TSST-1, inflames the adipocytes (fat tissues). As a result, inflamed adipocytes became insensitive to signals from insulin, rendering the fat tissues insulin-resistant.

Clinical observation

Their rabbit experiment was inspired by the observation that type II diabetics frequently have Staph overgrowth on their skin. This is, in part, because type II diabetics tend to gain weight. Their sweat glands increase as the weight increases — favoring the growth of S. aureus.

“As people gain weight, they are increasingly likely to be colonized by staph bacteria — to have large numbers of these bacteria living on the surface of their skin,” Schlievert clarified.

Staph skin overgrowth exposes the host to chronic levels of superantigen. Although they are at non-lethal doses, “about 10% of the superantigen can penetrate cells,” the professor added.

By measuring Staph levels on the skin of people with type II diabetes, Schlievert’s team found that the amount of Staph superantigen they were exposed to was proportional to the superantigen dosage that made the rabbits diabetic.

“The amount of superantigens present on the skin was consistent with the amount of superantigens required to cause elevated blood sugar and insulin-resistance in rabbits,” they wrote in Future Microbiology.

“We think it’s enough to cause the systemic, chronic inflammation that contributes to insulin resistance and diabetes,” said Schlievert.

Further, people with type II diabetes are 3x more vulnerable to Staph blood infection than non-diabetics, according to a study of 30,000 Danish medical records between 2000 and 2012. Staph blood infection indicates that S. aureus on the skin has breached the bloodstream. Though the Danish researchers attribute this finding to the poor immune response of type II diabetics, Staph skin overgrowth could have also played a part.

New Developments

Recent studies have continued to explore this connection. A 2022 review in Nature Reviews Endocrinology highlighted that chronic inflammation plays a critical role in the development of insulin resistance, especially in individuals who are overweight or obese.

As Schlievert’s team observed, S. aureus overgrowth is common in these individuals due to increased sweat production, which provides a conducive environment for the bacteria to thrive.

According to recent research in 2023, the skin microbiome, including S. aureus, has a significant influence on systemic health. In people with obesity and type 2 diabetes, skin colonization by S. aureus is often increased, and chronic exposure to its superantigens may exacerbate low-grade systemic inflammation.

Approaching causality?

“It’s true that about 50% of people with diabetes have skin colonization with staph compared to about 25% of people without diabetes, but that’s likely because of their diabetes — not the other way around,” critiqued Ignatius Fong, MD, Professor of Medicine and infectious disease specialist from the University of Toronto.

While that may be true, the ‘other way around’ may also be. This is evident in the rabbit experiment that provided a robust direction of causality.

Prof. Schlievert also claimed that “we fulfilled Koch’s postulates showing S. aureus is a cause of type II diabetes mellitus” in an academic review in Future Microbiology. Koch’s postulates — comprising 4 criteria — are widely used to determine whether a microbe causes a certain disease.

“It took years for the scientific community to agree that TSST-1 was causing toxic shock syndrome,” commented Prof. Schlievert. “It took a long time for people to believe that strep, another bacterium, was the cause of flesh-eating disease — which we found in 1987.”

“A major question remaining is: What percentage of type II diabetes do S. aureus and its superantigens cause?” the professor wrote. But they admit that “we don’t know the answer to this question.”

However, we should still be cautious in assigning causality based on animal experiments. It’s more likely that S. aureus is part of the cause as it’s a common bacterium inhabiting the human skin.

But it's unlikely to cause diabetes — a multifactorial disorder — by itself. Staph superantigens likely interact with other factors, such as physical activity or dietary choices, to ultimately determine if diabetes develops.