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Chip Device Simulates Human Gut Interactions

HuMix device

Top view of HuMix device (University of Luxembourg)

11 May 2016. A device simulating the human intestine was shown in lab tests to generate similar responses to interactions between gut microbes and cells, as found in humans and animals. The HuMix system — short for Human Microbial Cross Talk — developed by researchers at University of Luxembourg and University of Arizona, is described in today’s issue of the journal Nature Communications.

HuMix is a microfluidics, or lab-on-a-chip, device that offers a controlled environment to simulate interactions between the microbial communities in the gut and other key functions in the body. The microbiome, the name given to the aggregate of bacteria other microorganisms in the gut, is an emerging target for research on its interactions with the genome and development of disease anywhere in the body. Loss of equilibrium in the microbiome is already associated with diabetes, obesity, and inflammatory bowel disease, as well as some forms of cancer and neurodegenerative disorders.

Because of the highly complex nature of these interactions, developers of HuMix believe their device can better simulate functions in the human gut than lab animals with much simpler organs. The pharmaceutical industry could gain an early benefit from the device in preclinical drug testing, particularly for toxic adverse effects, where animal testing can be unreliable and human tests unethical.

HuMix was developed in the lab of Luxembourg systems biologist Paul Wilmes in the university’s Centre for Systems Biomedicine. Wilmes’s collaborators in the U.S. were led by Frederic Zenhausern, director of the Center for Applied Nanobioscience and Medicine at University of Arizona.

HuMix is about the rectangular size of a cocktail napkin, and has three layers, configured in spiral channels. The top layer contains nutrients that flow down to the middle layer containing a thin membrane where human intestinal epithelial or surface cells grow, while the bottom layer has bacteria. HuMix makes it possible to observe the interaction between the intestinal cells and bacteria in real time, and under realistic anaerobic conditions, where oxygen is lacking.

In their paper, the researchers report on tests of HuMix with Lactobacillus rhamnosus GG or LGG, a common probiotic strain sometimes used to treat gastrointestinal disorders, and Bacteroides caccae, a bacterial species that serves a healthy digestive function in the gut, but can cause infections elsewhere in the body. In tests with these bacteria, the team reports the bacteria were able to generate observable genomic, metabolic, and immunological responses from the human epithelial cells.

One of the responses documented in the tests was production of gamma-aminobutyric acid or GABA, a neurotransmitter in the brain that accumulated in the epithelial cells. GABA was produced in response to interactions with LGG bacteria, suggesting a signaling connection between the gut and nervous system.

Pranjul Shah, the paper’s first author, founded OrgaMime, a spin-off company from University of Luxembourg commercializing the HuMix device. OrgaMime is marketing a series of HuMix systems, called microGut,  linked together to simulate the entire gastrointestinal system. The authors filed a patent for the technology.

In the following video, Wilmes tells more about HuMix.

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