Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging. Academic Article uri icon

abstract

  • 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.

published proceedings

  • Int J Mol Sci

altmetric score

  • 0.5

author list (cited authors)

  • Noh, J. Y., Wu, C., DeLuca, J., Devaraj, S., Jayaraman, A., Alaniz, R. C., ... Sun, Y.

citation count

  • 8

complete list of authors

  • Noh, Ji Yeon||Wu, Chia-Shan||DeLuca, Jennifer AA||Devaraj, Sridevi||Jayaraman, Arul||Alaniz, Robert C||Tan, Xiao-Di||Allred, Clinton D||Sun, Yuxiang

publication date

  • February 2022

publisher