A Cultural Revolution in the Study of the Gut Microbiome

Irritable Bowel Syndrome

Inflammatory Bowel Diseases (IBD) such as ulcerative colitis and Crohn’s disease affecting gut microbiome impacts an estimated 1,000,000 Americans. If not managed early it can lead to life-threatening complications. Abnormal immune responses trigger these diseases, however issues relating to gut microbiome, intestinal epithelial cells, immune components and the gut’s rhythmic peristalsis motions can also exacerbate symptoms. Since, it is practically difficult to replicate the human gut microenvironment in the laboratory; scientists were at a loss in developing new therapies for treating IBDs.

In a first of its kind development, a team at the Wyss Institute for Biologically Inspired Engineering at Harvard University co-led by Wyss Institute Founding Director Donald Ingber, M.D., Ph.D., and Wyss Core Faculty member James Collins, Ph.D., has leveraged the Institute’s proprietary human-organs-on-chips technology to microengineer a model of human intestinal inflammation and bacterial overgrowth in a human-gut-on-a-chip. It will aid scientists to analyze how normal gut microbes and pathogenic bacteria contribute to immune responses. It will also help in investigating IBD mechanisms in a controlled model that recapitulates human intestinal physiology. The report was published in Proceedings of the National Academy of Sciences (PNAS) journal.

As per the report, the Wyss team has been able to show that the human gut-on-a-chip’s unique ability to co-culture intestinal cells with living microbes from the normal gut microbiome for up to two weeks, thereby allowing breakthrough insights into how the microbial communities flourishing inside our GI tracts contribute to human health and disease.

Hyun Jung Kim, Ph.D., former Wyss Technology Development Fellow and first author on the study said that till date it has been impossible to determine how exactly factors like abnormal interactions between gut microbes, intestinal epithelial cells and the immune system contribute to the development of intestinal bowel disease. The human gut-on-a-chip technology will be a game changer as it provides an ideal microenvironment for mimicking the natural conditions of the human intestines in a small-scaled, controllable in vitro platform.

Ingber remarked that the discovery of the microbiome and its significance represents a huge paradigm shift in our understanding of human health. Use of traditional culture methods and even more sophisticated organoid cultures have prevented the microbiome from being studied beyond a day or two. With the human gut-on-a-chip technology, not only the normal gut microbiome can be cultured for extended times, it will also help in analyzing contributions of pathogens and various other factors in triggering and proliferating IBDs.

Collins, a Termeer Professor of Medical Engineering and Science at the Massachusetts Institute of Technology said that there is much to be learned about IBD, as well as how antibiotics impact the microbiome. This technology is significant as it enables one to study in an isolated and controlled manner the complexity of the microbiome and the role different microbial species play in health and disease.

With the help of this technology it has been found that four small proteins that stimulate inflammation (called cytokines) work in tandem to trigger inflammatory immune responses that damage and irritate the bowel. Scientists can now explore the option of treating IBDs by “blocking” these cytokine proteins. The Wyss team also found that absence of peristaltic movement can lead to rampant overgrowth of bacteria completely independent of changes in fluid flow. This explains why some patients with IBD and other conditions develop bacterial overgrowth.

The Wyss team is of the opinion that the human gut-on-a-chip technology also holds promise for the field of precision medicine, where a patient’s own cells and gut microbiota could one day be cultured inside a gut-on-a-chip for testing different therapies and identifying an individualized treatment strategy.

Ingber said that with the help of this technology they hope to gain a much deeper understanding of underlying pathophysiological mechanisms that will hopefully lead to the development of novel and more effective therapies.

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References:

www.wyss.harvard.edu/viewpressrelease/233/

https://medicalxpress.com/news/2015-12-cultural-revolution-gut-microbiome.html