What part of the intestine is problematic matters more than inflammatory bowel disease subtype (Crohn’s disease vs ulcerative colitis), when it comes to genetic activity signatures in pediatric IBD.
Suresh Venkateswaran and Subra Kugathasan in the lab
That’s the takeaway message for a recent paper in Cellular and Molecular Gastroenterology and Hepatology (the PDF is open access) from gastroenterologist Subra Kugathasan and colleagues. His team has been studying risk factors in pediatric IBD that could predict whether a child will experience complications requiring surgery.
Kugathasan is professor of pediatrics and human genetics at Emory University School of Medicine and scientific director of the pediatric IBD program at Children’s Healthcare of Atlanta. He is also director of the Children’s Center for Transplantation and Immune-mediated Disorders.
“This study has demonstrated that tissue samples from the ileum and rectum of CD patients show higher molecular level differences, whereas in tissue samples from two different patients with the same type of disease, the molecular differences are low,” Kugathasan says. “This was an important question to answer, since IBD can be localized to one area, and the treatment responses can vary and can be tailored to a localized area if this knowledge is well known.”
Research associate Suresh Venkateswaran, PhD, is the first author on the CMGH paper.
“We see that the differences are not connected to genomic variations,” he says. “Instead, they may be caused by non-genetic factors which are specific to each location and disease sub-type of the patient.”
These findings have implications for other study designs involving molecular profiling of IBD patients. The authors believe the findings will be important for future design of locally acting drugs.
Intestinal inflammation in mice can be dampened by giving them a diet restricted in amino acids, the building blocks of proteins, researchers have found. The results were published online by Nature on Wednesday, MarchÂ 16.
The findings highlight an ancient connection between nutrient availability and control of inflammation. They also suggest that a low protein diet — or drugs that mimic its effects on immune cells — could be tools for the treatment of inflammatory bowel diseases, such as Crohnâ€™s disease or ulcerative colitis.
The research team, led by Emory Vaccine Center immunologist Bali Pulendran, discovered that mice lacking the amino acid sensor GCN2 are more sensitive to the chemical irritant DSS (dextran sodium sulfate), often used to model colitis in animals. This line of research grew out of the discovery by Pulendran and colleagues that GCN2 is pivotal for induction of immunity to the yellow fever vaccine.
â€œIt is well known that the immune system can detect and respond to pathogens, but these results highlight its capacity to sense and adapt to environmental changes, such as nutritional starvation, which cause cellular stress,â€ he says.
AÂ Emory News item on a helpful part of the microbiome focuses on how the same type of bacteria â€“ lactobacilli â€“ activates the same ancient signaling pathway in intestinal cells in both insects and mammals.Â It continues a line of research from Rheinallt Jones and Andrew Neish on how beneficial bacteria stimulate wound healing by activating ROS (reactive oxygen species).
Asma Nusrat, MD
A idea behind this research is: if we know what parts of the bacteria stimulate healing, perhaps doctors can deliverÂ that material, or something very close, to patients directly to treat intestinal diseases such as Crohn’s or ulcerative colitis.
This ideaÂ has advanced experimentally, as demonstrated byÂ twoÂ papers from Jones and Neishâ€™s frequent collaborator, Asma Nusrat, who recently moved from Emory to the University of Michigan. This team had shown that a protein produced by human intestinal cells called annexin A1 activates ROS, acting through the same N-formyl peptide receptors that bacteria do.
Nusrat told me Friday her team began investigatingÂ annexins a decade ago at Emory, and it was fortuitous that Neish was working on beneficial bacteria right down the hall, since it is now apparent that annexin A1 and the bacteria areÂ activating the same molecular signals.Â (Did you know there is an entire conference devoted to annexins? I didn’t until a few days ago.)
In aÂ secondÂ Journal of Clinical Investigation paper published this February, NusratÂ and herÂ colleagues show that intestinal cells release vesicles containing annexin A1 following injury. The wound closure-promoting effects of these vesicles can be mimicked with nanoparticles containing annexin A1. The nanoparticles incorporate a form of collagen, which targets them to injured intestinal tissue. Read more