Irritable Bowel Syndrome (IBS) affects an estimated 25–45 million people in the United States, drives roughly ~20–40% of gastroenterology visits, and imposes a major societal burden with annual U.S. costs estimated at ~$1.7–$10B in direct medical spending plus ~$20B in indirect costs from lost productivity and related impacts. Despite this, IBS remains poorly understood without definitive biochemical diagnostics or curative therapies. Here, we propose to deploy novel technology to better understand microbiome dysfunction in IBS that will lead to: 1) improved biochemical diagnostic markers and 2) rational, mechanism-based microbiome therapies.

While the gut microbiome is critical to human physiology with key roles in metabolism and immunity by co-processing of our dietary intake, the microbiome can become dysfunctional and directly lead to IBS symptoms. In most patients, a diet high in fiber supports a healthy microbiome and improves health outcomes without symptoms. In IBS, however, some fiber types are known to worsen symptoms of bloating, flatulence, and abdominal pain, with patients advised to restrict fermentable fiber intake and antibiotics are used as therapy to kill bacteria and prevent fermentation. 

Thus, it is likely that IBS symptoms are derived from disorders of gut microbiome fiber fermentation, however this remains understudied to date and we lack adequate tools to measure microbial fermentation in the clinic. To address this, we will leverage a combination of two recently developed ingestible capsule technologies (A real-time intestinal gas sensing technology and a regional microbiome sampling capsule) during dietary intervention studies in healthy subjects and IBS patients. This will allow us to triangulate microbial, chemical, and physiological features with unprecedented resolution to molecularly characterize microbiome dysfunction in IBS. We will employ in vitro and in silico modeling of fiber fermentation to predict gas and metabolite formation guided by the hypothesis that a significant portion of IBS patients lack Hydrogen and Carbon Dioxideconsuming organisms leading to bloating and abdominal pain. These findings will lead to new collaborations between the Department of Medicine and 3 basic science departments (Biology, Applied Physics, and Bioengineering) to describe fundamental principles of regional microbiome physiology and advance clinical care. These studies will enable a paradigm in which we employ high resolution regional microbiome
diagnostics to design precise and personalized microbiome therapies for IBS. We aim to find the right bacteria to give the right patients and match them with the right fiber type.