New research has suggested that inflammation in the gut can reach far beyond the digestive system to affect other areas, like skin. This work is helping to reveal the many biological mechanisms that link the microbial community in the gut to human health. The gut microbiome is thought to have a significant influence on many parts of the human body, and changes in the gut microbiome may increase the risk of a variety of disorders including asthma, multiple sclerosis, and arthritis. This latest research, published in Cell Reports, has shown how chronic intestinal inflammation known as colitis can lead to serious skin disorders that resemble infections but do not harbor pathogens. These findings may reveal more about how colitis-associated skin disorders arise, and how to treat them.
"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," said senior study author and dermatologist Tiffany Scharschmidt, MD. "The composition of bacteria on the skin didn't change. Instead, what changed was the skin's immune response to them."
We host many beneficial microorganisms that can help our bodies function. The immune system learns to live along with these so-called commensal bacteria, a tolerance that is established during infancy. In this study, the researchers have shown how interactions between the gut microbiome and immune system can lead to disruptions in that tolerance in another part of the body.
In this study, the researchers used a mouse model to induce colitis. When that happened, immune cells that can trigger inflammation called neutrophils invaded the skin, a phenomenon has also been observed in inflammatory bowel disease patients. In the mice, this activity required a molecule called IL-1, which is involved in controlling the immune response.
The scientists also found that colitis seems to disrupt the immune tolerance of microbes that is set up in early life, causing the immune system to attack microbial communities that it had previously accepted.
Immune tolerance relies on a balance between T regulatory cells, or Tregs, which are tolerant, and T effector cells, which can go on the attack; Tregs keep effectors under control. Staphylococcus epidermidis is typically a harmless microbe that is a normal part of the skin microbiome. But when colitis occurs, Treg levels are lowered compared to effectors. The researchers suggested that this change in the T cell balance leads to skin inflammation.
Further work showed that in mice are engineered so they do not respond to IL-1, neutrophils don't build up when colitis was induced, and they do not shows signs of inflammation in the skin.
IL-1 has a crucial role in lowering tolerance and promoting an inflammatory response, suggested Scharschmidt. If a more harmonious balance can be restored, it may have a therapeutic impact.
Sources: University of California, San Francisco, Cell Reports
