Artificial gut mimics microbiome reaction to drugs

A new “gut on a chip” will let scientists see how cells from individuals respond to certain drugs or immune therapies, allowing them to formulate personalized treatments.

With the new technology, researchers can analyze the complex interactions between human cells and the microbial ecosystems of the gut, predicting their effects on health or disease onset, and study the action of environmental exposure (such as irradiation), nutritional compounds, or drugs.

gut on a chip
(Credit: U. Arizona)

The Human-Microbial Cross-Talk model, or HuMiX, allows researchers to determine interactions with several drugs at a time and could replace the animal model, says project leader Frederic Zenhausern, professor at the Center for Applied NanoBioscience and Medicine at the University of Arizona College of Medicine – Phoenix.

“The mice model is not a good representation of the complex human gut biology,” he says.

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According to Zenhausern, the team is working to study “the impact of the gut-brain axis, which may be involved in cognition, but also in Alzheimer’s or Parkinson’s diseases.” Their work appears in Nature Communications.

With the HuMiX model, scientists can actually look at responses of human cells in relation to specific microbiome compositions, according to collaborator Paul Wilmes of the Luxembourg Center for Systems Biomedicine. “It’s a model that is much more relevant from a human disease and health perspective.”

For example, distinct bacterial species can be introduced into the artificial gut model, and scientists can study whether the organisms trigger or slow down inflammation or introduce immune cells and neurons together with the bacteria, Wilmes says. “We can also analyze how probiotics, dietary compounds, or drugs affect human physiology.”

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The core of the technology is a spiral-shaped nanofabricated chamber that has a thin, permeable polymer membrane separating bacteria and nutrients from human gastrointestinal cells, while still allowing communication between the layers.

The practical implications allow scientists to look at how different diets, along with different microbiome compositions, might affect human cell physiology.

“We can put in (to the model) cells from individuals and see how those cells respond to certain drugs and start really understanding how we might formulate drug therapies in a very personalized way,” Wilmes says.

Zenhausern says the development of tools for better characterizing the functional role of the human microbiome in human health has the potential to aid in the discovery of new treatments for obesity, inflammatory bowel disease, allergies, diabetes, cancer, and neurodegenerative diseases. The technology also could be a valuable tool for better understanding the role of microbials in the physical performance and cognitive function of soldiers in war, athletes, or other professionals under high-stress activities.

For their tests confirming the validity of HuMiX experiments, researchers used pure cultures of various bacterial strains with unprecedented control of the aerobic and anaerobic conditions required to co-culture host cells and microbial ecosystems. They then studied how the gene activity and metabolism of intestinal epithelial cells changed, depending on the bacterial strain.

A comparison of data from HuMiX with other research groups who obtained their data from humans or animals showed strong agreement, meaning HuMiX delivered an accurate portrayal of the cellular and molecular processes taking place in the human gut.

Researchers from the University of Luxembourg also contributed to the work. The intellectual property of the invention is co-owned by the University of Arizona and the University of Luxembourg. The team is working to protect the intellectual property and strategize ways to bring the device to market.

Source: University of Arizona

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Source: Futurity