Results from new research using mouse models suggest that a novel strategy for the treatment of inflammatory bowel disease may be possible. The new approach would precisely target metabolic pathways that are only active during intestinal inflammation, and could offer a substantial advance over current treatment modalities using broad-spectrum antibiotics. IBD, which includes conditions such as Crohn’s disease and ulcerative colitis, are characterized by changes in the composition of the gut microbiota, including uncontrolled proliferation of species in the Enterobacteriaceae family. The overgrowth is fueled via unique metabolic pathways that are present only in certain bacteria and active only during inflammation. This knowledge provided the key for the design of a novel therapeutic approach, according to co-corresponding author Sebastian Winter, PhD, a W.W. Caruth, Jr. Scholar in Biomedical Research at UT Southwestern Medical Center.
“Our results provide a conceptual framework for precisely altering the bacterial species that line the gut in order to reduce the inflammation associated with the uncontrolled proliferation of bacteria seen in colitis and other forms of inflammatory bowel disease,” Dr. Winter observed. In the study, published online last week in the journal Nature, a form of the heavy metal tungsten was administered to mice with colitis via soluble tungsten salt in their drinking water. This was found to selectively prevent Enterobacteriaceae blooms without affecting other beneficial gut bacteria. Further, Dr. Winter noted, “…our strategy only inhibits the bloom of Enterobacteriaceae during intestinal inflammation without getting rid of them entirely. This finding is important because in the proper ratios, Enterobacteriaceae also fulfill the role of resisting colonization by bacterial pathogens.” He stressed, however, that the work represents only a proof-of-concept that suggests the validity of a specific molecular target, and that treatment with heavy metals such as tungsten would be inappropriate due to the potential for serious neurological and reproductive adverse effects.
Read a news article about the findings.
The study abstract may be read here.
Posted on January 8, 2018