Here’s what your skin is trying to tell you about your health and gut…

A recent study conducted by researchers at UC San Francisco has uncovered the connection between gut inflammation and its impact on both the digestive system and the skin. The study sheds light on the crucial role played by specialized immune cells and the bacterial communities, known as microbiomes, residing in the gut and skin.

Scientists have increasingly recognized that disruptions to the gut microbiome can have far-reaching effects on the entire body. Such disturbances have been associated with an elevated risk of various diseases, including asthma, rheumatoid arthritis, and multiple sclerosis.

Published in Cell Reports, the study delved into how colitis, a chronic inflammation of the large intestine, can lead to debilitating skin conditions that resemble infections but do not involve skin pathogens.

Dermatologist Dr. Tiffany Scharschmidt, the senior author of the study, explained, “What we learned is that factors involved with gut inflammation are actually causing the skin to react differently to the microbes it’s already become accustomed to. The composition of bacteria on the skin didn’t change. Instead, what changed was the skin’s immune response to them.”

This finding could potentially help elucidate the mechanisms behind colitis-associated skin disorders.

The Diversity of Microbes:

Under normal circumstances, immune cells attack and eliminate invading pathogenic bacteria while coexisting with the well-behaved microbial members of the body’s microbiomes, known as “commensals.” This tolerance towards commensals is established during infancy.

Dr. Scharschmidt and colleagues sought to better understand how disruption of the immune-microbiome environment in the gut can disrupt microbiome tolerance in distant organs, such as the skin. This phenomenon is observed in various conditions falling under the category of inflammatory bowel disease (IBD), including colitis.

The research, led by former graduate student Dr. Geil Merana, focused on inducing colitis in adult mice and observing the response of the immune system and microbiomes in the gut and skin.

The team discovered that this induction allowed inflammatory immune cells called neutrophils to infiltrate the skin. In both mice and humans with IBD-associated skin disorders, this infiltration of neutrophils was dependent on a molecule called IL-1, which regulates immune responses.

The Disruption of Tolerance:

Another significant finding was that colitis appeared to reverse the tolerance established during early life towards specific commensal bacteria on the skin. Consequently, the immune system initiated inflammatory reactions against previously peaceful microbes.

The ability of the body to tolerate a particular bacterial species is maintained by balancing the functions of two types of immune cells with opposing roles. T regulatory cells (Tregs) promote tolerance, while T effector cells defend against foreign molecules or microbes. Tolerance is achieved when Tregs keep T effector cells in check.

The researchers focused on T cells targeting the harmless skin bacterium Staphylococcus epidermidis. They observed that colitis resulted in a lower ratio of Tregs to T effector cells. This deficit in Tregs, they concluded, was responsible for the subsequent skin inflammation.

To investigate further, colitis was induced in a group of mice with T cells unresponsive to IL-1. In contrast to the response seen in normal mice, the genetically modified mice did not experience an accumulation of neutrophils in the skin. The ratio of the two types of T cells remained unaffected, and no inflammation occurred.

According to Dr. Scharschmidt, these results highlight the pivotal role of IL-1 in tipping the balance from tolerance to an inflammatory response.

Promising avenues for future research and development lie in therapies that maintain a balanced T-cell response, noted Dr. Scharschmidt. Understanding the intricacies of skin reactions is the first step towards exploring new approaches to address this problem.

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