International journal of molecular sciences, 2022-02, Vol.23 (4), p.2219
2022
Details
- Autor(en) / Beteiligte
- Titel
- Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging
- Ist Teil von
- International journal of molecular sciences, 2022-02, Vol.23 (4), p.2219
- Ort / Verlag
- Switzerland: MDPI AG
- Erscheinungsjahr
- 2022
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1422-0067, 1661-6596eISSN: 1422-0067DOI: 10.3390/ijms23042219Titel-ID: cdi_doaj_primary_oai_doaj_org_article_6732c4564a7f43b49936c0abf6781266
- Format
- –
- Schlagworte
- Ablation, Age, Aging, Aging (artificial), Aging - metabolism, Animals, Bacteroidetes, Cardiovascular diseases, Colitis, Colitis - metabolism, Colon, Cytokines, Cytokines - metabolism, Dextran, Dextran sulfate, Dextrans, Diabetes, Diabetes mellitus (non-insulin dependent), Diabetes Mellitus, Type 2 - metabolism, Digestive system, Digestive tract, Disease, Dysbacteriosis, Dysbiosis - metabolism, Energy metabolism, Energy Metabolism - physiology, Feces, Firmicutes, Gastrointestinal Microbiome - physiology, Genotype & phenotype, Ghrelin, Growth hormone, growth hormone secretagogue receptor (GHS-R), Growth hormones, gut permeability, Homeostasis, Inflammation, Inflammation - metabolism, Inflammatory bowel disease, Inflammatory bowel diseases, Inflammatory Bowel Diseases - metabolism, Insulin Resistance - physiology, Intestinal microflora, Intestine, Male, Metabolism, Metabolites, Mice, Mice, Inbred C57BL, Mice, Knockout, microbiome, Microbiomes, Microbiota, Microbiota - physiology, Obesity - metabolism, Pathogenesis, Receptors, Ghrelin - metabolism, Rodents, ulcerative colitis