Living Human Gut-On-A-Chip Could Provide Insights Into Disorders And Help Evaluate Potential Treatments
Researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University have created a gut-on-a-chip microdevice lined by living human cells that mimics the structure, physiology, and mechanics of the human intestine -- even supporting the growth of living microbes within its luminal space. As a more accurate alternative to conventional cell culture and animal models, the microdevice could help researchers gain new insights into intestinal disorders, such as Crohn's disease and ulcerative colitis, and also evaluate the safety and efficacy of potential treatments. The research findings appear online in the journal Lab on a Chip. Building on the Wyss Institute's breakthrough "Organ-on-Chip" technology that uses microfabrication techniques to build living organ mimics, the gut-on-a-chip is a silicon polymer device about the size of a computer memory stick.
When the intestines are not able to properly process our diet, a variety of disorders can develop, with chronic diarrhea as a common symptom. Chronic diarrhea can also be inherited, most commonly through conditions with genetic components such as irritable bowel syndrome. Researchers in Norway, India, and at the HudsonAlpha Institute for Biotechnology have identified one heritable DNA mutation that leads to chronic diarrhea and bowel inflammation. Shawn Levy, Ph.D., faculty investigator at HudsonAlpha said, "Based on the effects seen from this one mutation, we are hopeful that the work will aid in understanding of much more common diseases like Crohn's and irritable bowel syndrome, which also have inflammation and diarrhea as symptoms." The Norwegian family studied for the paper published in The New England Journal of Medicine has 32 living members with a number of related inflammatory bowel conditions.
Researchers from the Hotchkiss Brain Institute (HBI) and the Snyder Institute for Chronic Diseases at the University of Calgary's Faculty of Medicine have discovered a pathway that may contribute to the symptoms related to Crohn's disease and ulcerative colitis, collectively known as Inflammatory Bowel Disease (IBD). This research is a major milestone in developing future drug therapies for those living with these debilitating disorders. The digestive process is complex. To coordinate the many functions involved in digestion, the gut has its own set of nerve cells (neurons), often called the "second brain". Crohn's disease is characterized by inflammation in the gut, leading to damage or death of millions of these neurons lining the gastrointestinal tract. As a consequence, patients are left with a host of debilitating symptoms including abdominal pain and numerous disruptive digestive conditions.
In a surprising result, Michigan State University researchers looking at the effects of diet on bowel disease found that mice on a calorie-restricted diet were more likely to die after being infected with an inflammation-causing bacterial pathogen in the colon. While research suggests inflammation associated with obesity may contribute to inflammatory bowel diseases such as colitis, the study results revealed a low-calorie diet may actually impair the immune system's ability to respond to infection, said Jenifer Fenton, assistant professor in the Department of Food Science and Human Nutrition. Additionally, the study found no connection that moderate obesity increased the severity of colitis in the mouse model. "The results are similar to the research from our department that shows consuming fewer calories make it harder to fight off the flu virus, " said Fenton, referring to recent work by colleague Elizabeth Gardner.
How Salmonella Avoids The Body's Immune Response Offers Approaches To Fighting Powerful Gut Infections
UC Irvine researchers have discovered how salmonella, a bacterium found in contaminated raw foods that causes major gastrointestinal distress in humans, thrives in the digestive tract despite the immune system's best efforts to destroy it. Their findings help explain why salmonella is difficult to eradicate and point to new approaches for possible treatments. Most people infected with salmonella suffer from diarrhea, fever and abdominal cramps for up to seven days before the infection resolves. Lead researcher Manuela Raffatellu, a UCI assistant professor of microbiology & molecular genetics, and colleagues identified a novel molecular mechanism that allows salmonella to survive. Results of their study appear in the March issue of Cell Host & Microbe. Pathogens like salmonella flourish and cause disease in humans through a process by which they acquire metal ions, such as zinc, from the body.