How an unbalanced skin microbiome can make you itch

The itchiness that comes with some annoying dermatological conditions might be caused by certain microbes on skin. In a study published November 22 in the journal Cell, a team of scientists found that a common skin bacterium called Staphylococcus aureus can result in itchiness by acting directly on the nerve cells. 

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This is the first time that scientists have observed how this microbe works to create itching sensations. The finding adds an important piece to the puzzle of why some common skin conditions like eczema often have a persistent itch. Eczema, also called atopic dermatitis, affects about 20 percent of children and 10 percent of adults in the United States. It usually causes the equilibrium of microorganisms that keep our skin healthy to be thrown out of balance. These conditions allow S. aureus to flourish, according to the study’s authors from Harvard Medical School.

Previously, dermatologists believed that the itchiness that accompanies eczema happened because of skin inflammation. The new paper shows that S. aureus causes itch by beginning a molecular chain reaction that ends in the urge to scratch the skin.

“We’ve identified an entirely novel mechanism behind itch—the bacterium Staph aureus, which is found on almost every patient with the chronic condition atopic dermatitis. We show that itch can be caused by the microbe itself,” study co-author and dermatologist Isaac Chiu said in a statement.

In the study, researchers exposed the skin of mice to S. aureus. Over several days, the animals developed an intensifying itch. The repeated scratching caused worsening skin damage that eventually spread beyond the original site of exposure.

The mice exposed to S. aureus also became hypersensitive to unharmful stimuli that would usually not cause the skin to itch. They were also more likely to develop abnormal itching in response to a light touch than the mice that were not exposed to the bacterium. This hyperactive response called alloknesis and it is common in patients struggling with chronic skin conditions that have persistent itch. 

Researchers then identified several enzymes that were released by the bacteria once it began to grow on the skin. They tested each enzyme to see if it triggered any itching. It turned out that S. aureus releases the bacterial enzyme protease V8, which then activates the protein PAR1. This protein is located on the nerve fibers that send signals from the skin to the brain, prompting the sensation of itchiness. 

PAR1 proteins are also present on certain blood cells and are involved in clotting. Anti-clotting medications that are already available can block the protein activation on the skin neurons, which gave the team a place to start to look for a treatment. 

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When the mice were given an anti-clotting medicine, the medication successfully blocked the activation of PAR1 on the skin’s nerve fibers. A critical step in the itch-scratch cycle was interrupted and the rodent’s symptoms appeared to be relieved. Scratching decreased. 

These findings could help lead to better oral medications or skin creams to treat persistent itching that comes with conditions linked to an imbalance in the skin microbiome, including eczema, prurigo nodularis, and psoriasis.

“Itch can be quite debilitating in patients who suffer from chronic skin conditions. Many of these patients carry on their skin the very microbe we’ve now shown for the first time can induce itch,” study co-author and immunologist Liwen Deng said in a statement. 

A question that the team plans to explore in future work is whether other microbes besides S. aureus can trigger itch.

“We know that many microbes, including fungi, viruses, and bacteria, are accompanied by itch but how they cause itch is not clear,” Chiu said.

Researchers are also exploring why microbes cause an itch and what evolutionary benefits the bacterium can gain from causing an itch. It could be that pathogens may hijack itch and other neural physical reflexes to their advantage. Earlier studies have shown that the tuberculosis bacterium directly activates the vagal neurons to cause cough, which might enable the bacteria to spread from one host to another. 

“It’s a speculation at this point, but the itch-scratch cycle could benefit the microbes and enable their spread to distant body sites and to uninfected hosts,” Deng said. “Why do we itch and scratch? Does it help us, or does it help the microbe? That’s something that we could follow up on in the future.”