Basic and translational research paves the way for breakthroughs that can ultimately change patient care. Three new studies from Cellular and Molecular Gastroenterology and Hepatology (CMGH) — AGA’s basic and translational open-access journal — provide a glimpse into future treatment strategies for stomach ulcers, inflammatory bowel disease and alcoholic liver disease. Please find summaries below.
Healing Stomach Ulcers Through Stem Cell Transplantation
Ulcers of the stomach are more common as we age due to a variety of changes, including reduced ability to heal small injuries. Engevik and colleagues show that gastric stem cells isolated from young mice can be transplanted into sites of injury within the stomachs of older mice, and that this results in accelerated repair. The ability of the transplanted young mouse cells, but not stem cells from older mice, to differentiate into a specialized cell type, termed SPEM, which is central to the healing process, appears to be a central component of this. While more work must be done, it is clear that this approach, or other means of inducing older cells to differentiate into SPEM, would be powerful in treatment of gastric injury.
Rethinking the Role of the Gut Microbiome in IBD
The intestinal microbiome has been the subject of intense scientific and lay interest over the past decade, and changes have been correlated with disease states. Most of this work has, however, relied on analyses of microbes within stool, which may not be representative of microbial populations that interface directly with the intestinal lining, i.e. mucosal surface. Further, characterization of stool microbes does not allow analysis of differences that may be present in separate regions of the intestine. Li and colleagues analyzed microbial proteins at the surface of six separate sites within the colon of healthy subjects and those with Crohn’s disease or ulcerative colitis. The data show that microbial populations at mucosal surfaces are related, but distinct, in separate regions of the colon. This suggests that we must change our view of the microbiome as a soup in which all components are present in equal proportions at all sites to that of a mosaic composed of networks reflecting local mucosal ecology. Such understanding is essential as efforts to manipulate the microbiome for therapeutic purposes continue.
Hydrazine Shows Potential as Therapy for Acute Alcoholic Liver Disease
Liver disease is caused by many disorders and toxic agents, of which alcohol is the most common. However, the underlying cellular processes that cause widespread damage, which can lead to cirrhosis, are not well defined. Chen and colleagues demonstrates that acrolein — a byproduct of alcohol consumption that is increased with increased dietary intake of polyunsaturated fatty acids — mediates many of the damaging effects of alcohol on the liver. Hydrazine — an acrolein scavenger in clinical use — protected mice from the damaging effects of alcohol, suggesting that hydralazine or similar drugs might be potential therapies in acute alcoholic liver disease.
Source: American Gastroenterological Association
- Wei-Yang Chen, Jingwen Zhang, Smita Ghare, Shirish Barve, Craig McClain, Swati Joshi-Barve. Acrolein Is a Pathogenic Mediator of Alcoholic Liver Disease and the Scavenger Hydralazine Is Protective in Mice. CMGH Cellular and Molecular Gastroenterology and Hepatology, 2016; DOI: 10.1016/j.jcmgh.2016.05.010
- Xiaoxiao Li, James LeBlanc, David Elashoff, Ian McHardy, Maomeng Tong, Bennett Roth, Andrew Ippoliti, Gildardo Barron, Dermot McGovern, Keely McDonald, Rodney Newberry, Thomas Graeber, Steve Horvath, Lee Goodglick, Jonathan Braun. Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel Disease. CMGH Cellular and Molecular Gastroenterology and Hepatology, 2016; DOI:10.1016/j.jcmgh.2016.05.003
- Amy C. Engevik, Rui Feng, Eunyoung Choi, Shana White, Nina Bertaux-Skeirik, Jing Li, Maxime M. Mahe, Eitaro Aihara, Li Yang, Betsy DiPasquale, Sunghee Oh, Kristen A. Engevik, Andrew S. Giraud, Marshall H. Montrose, Mario Medvedovic, Michael A. Helmrath, James R. Goldenring, Yana Zavros. The Development of Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) During Gastric Repair Is Absent in the Aged Stomach. CMGH Cellular and Molecular Gastroenterology and Hepatology, 2016; DOI:10.1016/j.jcmgh.2016.05.004