Wake Forest School of Medicine, Department of Pathology, Winston-Salem, USA.
University of North Carolina at Charlotte, Department of Bioinformatics and Genomics, Charlotte, USA.
Sci Rep. 2018 Jul 27;8(1):11373. doi: 10.1038/s41598-018-29473-9.
Monkeys demonstrate gastrointestinal barrier dysfunction (leaky gut) as evidenced by higher biomarkers of microbial translocation (MT) and inflammation with ageing despite equivalent health status, and lifelong diet and environmental conditions. We evaluated colonic structural, microbiomic and functional changes in old female vervet monkeys (Chlorocebus aethiops sabeus) and how age-related leaky gut alters responses to Western diet. We additionally assessed serum bovine immunoglobulin therapy to lower MT burden. MT was increased in old monkeys despite comparable histological appearance of the ascending colon. Microbiome profiles from 16S sequencing did not show large differences by age grouping, but there was evidence for higher mucosal bacterial loads using qPCR. Innate immune responses were increased in old monkeys consistent with higher MT burdens. Western diet challenge led to elevations in glycemic and hepatic biochemistry values only in old monkeys, and immunoglobulin therapy was not effective in reducing MT markers or improving metabolic health. We interpret these findings to suggest that ageing may lead to lower control over colonization at the mucosal surface, and reduced clearance of pathogens resulting in MT and inflammation. Leaky gut in ageing, which is not readily rescued by innate immune support with immunoglobulin, primes the liver for negative consequences of high fat, high sugar diets.
猴子表现出胃肠道屏障功能障碍（肠漏），这表现为随着年龄的增长，尽管健康状况相当，且终生的饮食和环境条件相同，微生物易位（MT）和炎症的生物标志物更高。我们评估了老年雌性长尾猕猴（Chlorocebus aethiops sabeus）的结肠结构、微生物组和功能变化，以及年龄相关的肠漏如何改变对西方饮食的反应。我们还评估了血清牛免疫球蛋白治疗以降低 MT 负担。尽管升结肠的组织学外观相似，但在老年猴子中 MT 增加。16S 测序的微生物组图谱没有因年龄分组而显示出很大差异，但 qPCR 显示出更高的粘膜细菌负荷的证据。固有免疫反应在老年猴子中增加，这与更高的 MT 负担一致。西方饮食挑战仅导致老年猴子的血糖和肝功能生化值升高，而免疫球蛋白治疗在降低 MT 标志物或改善代谢健康方面无效。我们解释这些发现表明，衰老可能导致粘膜表面定植的控制能力降低，以及清除病原体的能力降低，导致 MT 和炎症。衰老时的肠漏不易通过免疫球蛋白的固有免疫支持来挽救，这使肝脏容易受到高脂肪、高糖饮食的负面影响。
