What the research is about
Hand, foot and mouth disease is a common viral infection that mainly affects young children. It is best known for causing blisters and rashes on the hands, feet, and inside the mouth.
One of the viruses that causes the disease is Enterovirus A71 (EV-A71). After entering the body through the mouth, the virus first multiplies in the intestine and is then excreted in stool. Although most patients recover within a few days, the virus can still be detected in stool samples for two to four weeks after symptoms begin.
In other words, the virus remains in the intestine long after the illness appears to be over. Surprisingly, however, most patients do not develop diarrhea or other intestinal symptoms. Why this happens has remained a mystery for many years.
Researchers have long tried to answer this question, but there has been a major obstacle. Conventional cell lines used for virus research are damaged within just a few days after infection, making it impossible to reproduce and observe the weeks-long infection seen in patients.
To overcome this challenge, a research team led by Professor Kazuo Takayama at Institute of Science Tokyo (Science Tokyo) developed a gut-on-a-chip, or intestinal microphysiological system (MPS), using human pluripotent stem cells. This model closely mimics the human intestine, allowing the team to recreate EV-A71 infection under conditions much closer to those in the human body.
Why this matters
Using the gut-on-a-chip, the researchers observed something that had never been seen before. EV-A71 continued to multiply for 14 days, yet the intestinal cells remained largely undamaged. This finding matches what doctors see in real patients, who rarely develop diarrhea despite carrying the virus in their intestines.
The team also discovered that infected intestinal cells did not mount a sufficient interferon response-one of the body's key antiviral defense mechanisms. This suggests that EV-A71 may be able to evade the body's immune defenses, allowing it to continue multiplying for a long time without seriously damaging intestinal cells.
What's next
There are currently no approved treatments specifically for EV-A71 infection. By recreating the 14-day infection that occurs in patients, the gut-on-a-chip provides a more realistic platform than conventional laboratory models for evaluating potential new medicines.
In the future, this technology may also help researchers understand how the virus spreads from the intestine to other organs, bringing new insights into the disease and supporting the development of better treatments.
Comment from the researcher
Our goal was to reproduce, as faithfully as possible, what actually happens in the intestines of patients. We hope this gut-on-a-chip model will deepen our understanding of hand, foot and mouth disease and eventually contribute to the development of new treatments.
(Kazuo Takayama, Professor, Department of Synthetic Human Body System, Medical Research Laboratory, Institute of Integrated Research, Institute of Science Tokyo)
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