| Autor: |
Noh JY; Department of Nutrition, Texas A&M University, College Station, TX 77843, USA., Wu CS; Department of Nutrition, Texas A&M University, College Station, TX 77843, USA., DeLuca JAA; Department of Nutrition, Texas A&M University, College Station, TX 77843, USA., Devaraj S; Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA., Jayaraman A; Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843, USA., Alaniz RC; Department of Microbial Pathogenesis and Immunology, Texas A&M University Health Science Center, College Station, TX 77843, USA., Tan XD; Department of Pediatrics, Ann & Robert H. Lurie Children's Hospital of Chicago, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA., Allred CD; Department of Nutrition, Texas A&M University, College Station, TX 77843, USA.; Department of Nutrition, University of North Carolina at Greensboro, Greensboro, NC 27412, USA., Sun Y; Department of Nutrition, Texas A&M University, College Station, TX 77843, USA.; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. |
| Abstrakt: |
Chronic low-grade inflammation is a hallmark of aging, which is now coined as inflamm-aging. Inflamm-aging contributes to many age-associated diseases such as obesity, type 2 diabetes, cardiovascular disease, and inflammatory bowel disease (IBD). We have shown that gut hormone ghrelin, via its receptor growth hormone secretagogue receptor (GHS-R), regulates energy metabolism and inflammation in aging. Emerging evidence suggests that gut microbiome has a critical role in intestinal immunity of the host. To determine whether microbiome is an integral driving force of GHS-R mediated immune-metabolic homeostasis in aging, we assessed the gut microbiome profiles of young and old GHS-R global knockout (KO) mice. While young GHS-R KO mice showed marginal changes in Bacteroidetes and Firmicutes, aged GHS-R KO mice exhibited reduced Bacteroidetes and increased Firmicutes, featuring a disease-susceptible microbiome profile. To further study the role of GHS-R in intestinal inflammation in aging, we induced acute colitis in young and aged GHS-R KO mice using dextran sulfate sodium (DSS). The GHS-R KO mice showed more severe disease activity scores, higher proinflammatory cytokine expression, and decreased expression of tight junction markers. These results suggest that GHS-R plays an important role in microbiome homeostasis and gut inflammation during aging; GHS-R suppression exacerbates intestinal inflammation in aging and increases vulnerability to colitis. Collectively, our finding reveals for the first time that GHS-R is an important regulator of intestinal health in aging; targeting GHS-R may present a novel therapeutic strategy for prevention/treatment of aging leaky gut and inflammatory bowel disease. |
