Modeling malnutrition with microfluidics

Environmental enteric dysfunction (EED) is a chronic intestinal disease that affects millions of children in low- and middle-income countries. It’s related to malnutrition, but some patients don’t get better even with dietary supplements, so researchers want a better understanding of the disease’s biological mechanisms. A group from Harvard University’s Wyss Institute has now turned their expertise in microfluidic organ-on-a-chip technology towards achieving that understanding. By making intestine chips with cells from EED patients collected by collaborators at Aga Khan University, the researchers were able to simulate key genetic and structural features of EED. Cicely W. Fadel, a neonatal and pediatric disease specialist at Beth Israel Deaconess Medical Center, who co-led the project as a clinical fellow at Wyss, presented the research on Wednesday during a talk at ACS Fall 2022 in the Division of Agricultural and Food Chemistry. The team also published its work in Nat. Biomed. Eng. (2022, DOI: 10.1038/s41551-022-00899-x).

The researchers wanted to see how well their chip-based model could mimic features of EED in the lab. They found that chips with cells from EED patients showed numerous gene-expression patterns associated with the disease, even when cultured in a nutrient-rich medium. And depriving the cells of niacinamide and tryptophan—two nutrients implicated in clinical studies of the disease—led to dramatic structural and nutrient-uptake changes in the intestinal tissue on the chips, as well as hundreds more gene-expression patterns that resembled active EED. “To be able to read that out and see it mimic what you see in a clinical biopsy was pretty amazing to me,” Fadel said. She said the Wyss team is now working on studying microbiome effects on EED chips.