Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging.
Novel Role of Ghrelin Receptor in Gut Dysbiosis and Experimental Colitis in Aging.
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DOI：
10.3390/ijms23042219
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发表时间：
2022-02-17
影响因子：
5.6
通讯作者：
Sun Y
中科院分区：
文献类型：
--
作者：
Noh JY;Wu CS;DeLuca JAA;Devaraj S;Jayaraman A;Alaniz RC;Tan XD;Allred CD;Sun Y
慢性低度炎症是衰老的标志，现在被称为炎症老化。炎症性衰老会导致许多与年龄相关的疾病，如肥胖、2型糖尿病、心血管疾病和炎症性肠病（IBD）。我们已经证明，肠道激素ghrelin通过其受体生长激素促分泌受体（GHS-R）调节能量代谢和衰老过程中的炎症。越来越多的证据表明，肠道微生物群在宿主肠道免疫中起着至关重要的作用。为了确定微生物组是否是衰老过程中GHS-R介导的免疫代谢稳态的整体驱动力，我们评估了年轻和老年GHS-R全局敲除（KO）小鼠的肠道微生物组谱。年轻的GHS-R KO小鼠显示出拟杆菌门和厚壁菌门的微小变化，而年老的GHS-R KO小鼠显示出减少的拟杆菌门和增加的厚壁菌门，具有疾病易感的微生物群特征。为了进一步研究GHS-R在衰老过程中肠道炎症中的作用，我们用葡聚糖硫酸钠（DSS）诱导年轻和老年GHS-R小鼠急性结肠炎。GHS-R KO小鼠表现出更严重的疾病活动评分，更高的促炎细胞因子表达，以及紧密连接标记物的表达降低。这些结果表明，GHS-R在衰老过程中微生物组稳态和肠道炎症中起重要作用；抑制GHS-R会加剧衰老过程中的肠道炎症，增加对结肠炎的易感性。总之，我们的发现首次揭示了GHS-R是衰老过程中肠道健康的重要调节因子；靶向GHS-R可能为预防/治疗老化性漏肠和炎症性肠病提供一种新的治疗策略。
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.
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影响因子：
82.9
作者：
Barcena, Clea;Valdes-Mas, Rafael;Lopez-Otin, Carlos
通讯作者：
Lopez-Otin, Carlos
影响因子：
5.5
作者：
Albert, Eric J.;Marshall, Jean S.
通讯作者：
Marshall, Jean S.
影响因子：
5.8
作者：
Gnanapavan, S;Kola, B;Korbonits, M
通讯作者：
Korbonits, M
DOI：
10.1161/circgenetics.114.000219
发表时间：
2015-02
期刊：
Circulation. Cardiovascular genetics
影响因子：
--
作者：
Griffin JL;Wang X;Stanley E
通讯作者：
Stanley E
影响因子：
3.5
作者：
De Smet, B.;Thijs, T.;Depoortere, I.
通讯作者：
Depoortere, I.