Skin wounds have more far-reaching consequences than previously thought, and their effects run more than just skin deep – they can penetrate all the way to the gut.
We know there is some connection between the health of our outer and inner organs – people with skin diseases such as atopic dermatitis or psoriasis often like food allergies and inflammatory bowel disease, and they carry different intestinal microbes than people without the skin conditions. The bias has been to assume that the gut influences the skin, says at the University of California, San Diego.
But Gallo and his colleagues tested the opposite hypothesis in mice and found that skin injury affects the gut microbiome.
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To see whether skin injury altered intestinal microbes, Gallo’s team cut 1.5-centimetre-long incisions in the skin of some mice and left some unharmed. They then isolated and sequenced germs from the rodents’ faeces.
The two groups carried different microbes in their guts – wounded mice had fewer beneficial microorganisms, such as Bacillus clausii, and more harmful disease-causing bacteria, including Enterorhabdus caecimuris. This observation was “unexpected”, says Gallo.
To confirm that skin injury was the cause of the altered gut microbiome, the researchers repeated their experiments by injuring mice in another way: tweaking their genes to release an enzyme that breaks down the molecule hyaluronan, which maintains the skin’s water content. Again, mice with damaged hyaluronan had different gut bacteria than those with intact hyaluronan. In fact, the researchers suspect this molecule could be contributing to the “skin-gut axis”: a skin injury can release fragments of hyaluronan, which can trigger an immune response in the gut and shift its gene expression to alter its microbiome.
Next, the researchers tested mice from both experiments to see how these microbiome changes affected disease risk. When they gave the mice a drug known to cause the digestive disorder colitis, the rodents with skin wounds and those with damaged hyaluronan showed a higher disease severity than the control groups. The researchers then transplanted microbes from rodents’ faeces into germ-free mice that didn’t have their own microorganisms. Animals that received a transplant from the injured or genetically altered mice showed increased susceptibility to colitis compared with mice that got microbes from the control groups. These results indicated that the skin changes had indeed shifted the gut microbiome in a way that increased disease risk.
These findings are “very interesting”, says at the University of South Florida. He speculates that cortisol – a hormone released due to stress after an injury and known to affect the microbiome – could play a role in this skin-gut axis. He also thinks it is likely that such a skin-gut axis exists in humans.
Gallo expects the same, saying the next steps for this work will be human clinical studies. He hopes this finding can help design therapies aimed at controlling skin conditions in order to improve gut health.
Nature Communications
