A chronic gut disorder that occurs in regions with poor sanitation disrupts intestinal immune responses and impairs oral vaccine effectiveness, according to research led by UPMC Children’s Hospital of Pittsburgh and University of Pittsburgh School of Medicine scientists.
The finding, published in Immunity, is important because oral vaccines delivered by liquid drops to the mouth, such as polio and rotavirus vaccines, are especially useful in low-income countries that may not have healthcare workers trained in administering vaccines through needles. They also may stimulate better local immunity in the gut, which is key for fending off diseases contracted by contaminated food and water — including some of the very infections that contribute to the gut disorder, called environmental enteric dysfunction, or EED.
“It is tragic that the exact vaccines that might help prevent EED don’t work in children who have the disease,” said Timothy Hand, PhD, Assistant Professor of Pediatrics and Immunology at the R.K. Mellon Institute for Pediatric Research at UPMC Children’s and Director of Pitt’s Gnotobiotic Animal Core Lab.
EED is caused by malnutrition and chronic gastrointestinal infection from contaminated food and water. Infection with viruses, parasites or bacteria combined with poor diet can trigger gut inflammation and damage the finger-like projections called villi that help absorb nutrients from food.
Further experiments indicated that oral vaccine failure was mediated by gut microbiome. In response to microbiome-associated inflammation, T regulatory (Treg) cells accumulate in the small intestine.
“Treg cells arise because there’s too much inflammation and they help tamp down that inflammation,” said Hand. “But unfortunately, a side effect is that they prevent local accumulation of vaccine-specific CD4+ T cells.”
When the team used antibiotics to eliminate gut bacteria, vaccine effectiveness was restored.
According to Hand, these findings support the idea that targeting the microbiome could help treat EED and improve vaccine success in children.
EED is rare in resource-rich countries but common in poorer countries that lack sewage systems and sanitation. About 150 million children worldwide live in conditions that put them at risk of getting the disease.