How the Gut Microbiome May Help Us Prevent IBD

Breakthroughs in basic and translational research have the potential to change the lives of patients suffering from disease. In this Cellular and Molecular Gastroenterology and Hepatology (CMGH) research update, we highlight the most noteworthy research recently published in the journal, including a study offering the first example of a preventative approach to inflammatory bowel disease (IBD) therapy. We also look at how high altitude levels impact progression of IBD. And finally we take a look inside the pig and its role in GI research.

Please find summaries below. To learn more about any of the studies summarized here, or to speak with the study authors, please email [email protected].

First Look at a Preventive Approach to IBD Therapy
A Disease-Associated Microbial and Metabolomics State in Relatives of Pediatric Inflammatory Bowel Disease Patients
By Jonathan P. Jacobs, et al.

While previous studies have speculated that changes to the gut microbiome cause disease, these have only assessed healthy or diseased subjects and not proved cause and effect. However, this study by Jonathan P. Jacobs and colleagues directly links a disease-associated microbiome to disease risk in genetically- and environmentally-susceptible individuals. The authors report that the microbiome is altered in a disease-associated pattern, also known as dysbiosis, in some healthy relatives of pediatric IBD patients. The subset of relatives with dysbiosis had biochemical evidence signaling they were in a pre-disease state, i.e. increased fecal calprotectin despite no clinical symptoms. If future studies show that the healthy relatives with dysbiosis have a clinically significant increased risk of developing IBD, it may be possible to intervene before disease onset. Such an intervention could be aimed at restoring a normal microbiome or at other aspects of intestinal health, and would be the first example of a preventative approach to IBD therapy.

How High Altitude Levels Impact Progression of IBD
Hypoxia Positively Regulates the Expression of pH-Sensing G-Protein–Coupled Receptor OGR1 (GPR68)
By Cheryl de Vallière, et al.

Inflammation is accompanied by reduced oxygen delivery, or hypoxia, within the intestinal lining. Hypoxia has been shown to modify protein expression patterns that may, in turn, modify colitis progression. For example, high altitude exposure, which reduces oxygen delivery, can elicit IBD relapses. Cheryl de Vallière and colleagues report that, in IBD patients, but not healthy volunteers, exposure to simulated high altitude conditions increased expression of cell surface proteins that can sense local environmental acidification. These may be activated by local inflammation-associated acidification to trigger intracellular signaling pathways that lead to disease progression in IBD. Direct targeting of pathways that allow local acid sensing may have therapeutic benefit in both IBD and ischemic enterocolitis, a condition that occurs when blood flow to part of the large intestine is reduced.

Insights from Inside the Pig
Large Animal Models: The Key to Translational Discovery in Digestive Disease Research
By Amanda Ziegler, et al.

The use of animal models has been instrumental in studying mechanisms of digestive pathophysiology, but there may be no better model than the pig, according to Ziegler and colleagues’ review. The pig GI tract shares a number of similarities with the human GI tract that rodents do not, and in certain settings offers distinct advantages for studying GI physiology and pathophysiology. The pig has provided important tools and insight in intestinal ischemia/reperfusion injury, intestinal mucosal repair, as well as new insights into esophageal injury and repair. Porcine model development has taken advantage of the size of the animal, allowing increased surgical and endoscopic access. In addition, cellular tools such as the porcine IPEC-J2 intestinal cell line and porcine enteroids are providing the methodology to translate basic science findings using in depth mechanistic analyses. The authors believe that porcine models hold great promise for the future of clinically relevant digestive disease research.

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For all of the articles highlighted here, the authors have no conflicts to disclose.

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