chip device cells
CREDIT: Wyss Institute at Harvard University

A high-tech laboratory chip has revealed how poor diet and genetics interact to drive a chronic intestinal inflammatory condition in children.

The microengineered device highlighted nearly 300 genes whose expression was altered in intestinal tissue taken from children with environmental enteric dysfunction (EED) compared with healthy individuals.

These differences were even greater when the cells were grown in conditions that mimicked a poor nutritional environment.

Reporting in the journal Nature Biomedical Engineering, the researchers believe their in vitro model could help gain further insights into the course of this disease, as well as develop potent therapeutics.

“The Intestine Chip also could provide a platform for personalized medicine and nutrition when cultured with clinical biopsies, enabling personalized (patient‐specific) digestion, absorption, and allergic reactions to be assessed for different nutrients without putting the patient in danger,” they suggest.

EED is suffered by millions of children in low- and middle-income countries and is associated with malnutrition, stunted growth and cognitive impairment.

Oral vaccines are also less effective in children with the condition, leaving them exposed to preventable disease.

To investigate the disease further, researchers constructed an intestinal chip is made of a flexible polymer with parallel hollow microfluidic channels, one lined human intestinal epithelial cells and the other with human blood vessels.

These were separated by a permeable membrane through which nutrients and chemical signals could pass, with the cells kept alive using a nutrient medium in place of blood.

The study showed that 287 genes, including those associated with inflammation and intestinal injury, were expressed differently in the EED cells compared with healthy cells, with 86 upregulated and 201 downregulated.

Comparing the gene expression profile of the EED chips with those from patients with the disease who did not respond to nutritional intervention revealed some overlap, particularly a shared downregulation of genes encoding metallothionein proteins.

The researchers then compared healthy and EED chips grown in a nutrient-deficient medium lacking the essential amino acid tryptophan and the vitamin niacin in the form of niacinamide.

Whereas healthy chips grown in the nutrient-deficient medium had 690 genes that showed different expression compared with those receiving complete nutrition, for the EED chips this was observed in 969 genes.

Notably, six of the top ten genes that were upregulated in the clinical gene EED signature of patient tissue samples were shared with the EED chips that were cultured in the nutrient-deficient medium.

“The agreement between our nutrient-deficient EED Chip signature and the signature found in human patients was really exciting,” said researcher Cicely Fadel, from the Wyss Institute for Biologically Inspired Engineering, at Harvard University in Boston, Massachusetts, USA.

“We are not only able to recreate EED intestinal form and function, but we are also doing it using the same genetic pathways that are operating in human patients.

“That opens up the possibility that we could test drugs and other treatments on the EED Chip and get a response that could be similar to what you would see in patients.”

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