Could microbiome research tool revolutionize drug development?

LUXEMBOURG CITY, Luxembourg—The human microbiome as an area of research for potential therapeutic value continues to gain popularity and, in that vein, the University of Luxembourg recently announced the publication of a research article in the scientific journal Nature Communications based on research on the interaction between microorganisms in the gut and the human body through the development of the artificial Human-Microbial X(cross)-talk model, or HuMiX.

HuMiX represents an organ-on-a-chip model for the human gastrointestinal tract, and it has been developed to study the interaction between the microbiome, the community of all microbial organisms that live in and on our body and the human host—all in vitro. The model and resulting insights are expected to help provide a better understanding of whether changes in the gut’s microbiome cause disease, or if such changes are a consequence of the disease.

According to the university, HuMiX is the only model able to replicate the community of microorganisms in the gut while also allowing the study of their impact on human cell physiology, noting, “This technological breakthrough has not only the potential to change the way patients are given drugs by prescreening their effects on patient-derived cells and microbiota outside of the body, but also open up a new market segment for HuMiX in clinical drug development.”

Commenting on the article, Dr. Paul Wilmes, principal investigator at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg and senior author on the paper said in a statement: “Insights into the function of the human microbiome are a key to our understanding of human health and disease. By mimicking its function and the repercussions of distinct microbiota on human cells, we are now able to better understand the gut microbiome and also how it reacts to, for example, distinct drugs or dietary regimes.”

The key benefit of HuMiX technology is that it can help determine a drug’s suitability in humans and improve their overall success in the drug development pipeline. The model reportedly will for the first time allow preclinical testing in an environment that is analogous to the human system. Animal models, such as germ-free mice, exhibit important limitations with respect to the topology of their gastrointestinal tract, their diet and, importantly, their immune system.

Asked whether this technology will replace the use of animals in the drug development process, Wilmes tells DDNews, “Our precise aim is to have HuMiX at least partially replace the use of animals in research and in the drug development process. From our point of view it is essential to get human-relevant readouts (which HuMiX provides) as humans are of course quite different from, say, a mouse. With respect to the human microbiome in particular, important differences are apparent—most notably a different microbiome composition in mice, a greatly differing gut topology, a different diet and a quite different immune system.”

Dr. Pranjul Shah, now business development and innovation expert at the LCSB and first author of the study, sees clear economic potential in the technology and is preparing as entrepreneur-in-residence for a spin-off company—OrgaMime.

“The human microbiome market is one of the fastest growing niche markets at the interface of therapeutics and diagnostics. With the broad focus of the microbiome industry, even at pessimistic estimates, the industry is expected to reach $658 million by 2023,” said Shah in the news release about the article’s publication. “HuMiX is well positioned to be an enabling technology for a range of drug discovery programs at newly founded start-ups, pharma as well as nutraceutical companies. It has the potential to help further understand and consequently aid in the discovery of new treatments for obesity, inflammatory bowel disease, diabetes, cancer, and neurodegenerative diseases.”

The published paper is the result of an interdisciplinary collaboration between scientific teams at the LCSB, the Center for Applied NanoBioscience and Medicine at the University of Arizona and the Department of Infection and Immunity at the Luxembourg Institute of Health.

As to how they came together, Wilmes says, “I met Prof. Frederic Zenhausern [of the University of Arizona] at a meeting and as I had an interest in microfluidics for high-throughput cell culture. We got talking and soon decided to collaborate together to develop HuMiX. The collaboration with the Department of Infection and Immunity at the Luxembourg Institute of Health stems from the fact that Dr. Carole Devaux there has a long-standing research interest focused on HIV infection in the gut. Given her expertise and research interests, we have collaborated with her group on inclusion of immune cells in the HuMiX model for ultimately modeling HIV infection in the gut.”