Division of Infectious Diseases, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Center for Gastrointestinal Biology and Disease, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Center for Global Health, Division of Infectious Diseases and International Health, Department of Medicine, University of Virginia, Charlottesville, Virginia.
Cell Mol Gastroenterol Hepatol. 2019;7(3):692-707. doi: 10.1016/j.jcmgh.2018.12.006. Epub 2019 Jan 7.
Environmental enteric dysfunction (EED) (also referred to as environmental enteropathy) is a subclinical chronic intestinal disorder that is an emerging contributor to early childhood malnutrition. EED is common in resource-limited settings, and is postulated to consist of small intestinal injury, dysfunctional nutrient absorption, and chronic inflammation that results in impaired early child growth attainment. Although there is emerging interest in the hypothetical potential for chemical toxins in the environmental exposome to contribute to EED, the propensity of published data, and hence the focus of this review, implicates a critical role of environmental microbes. Early childhood malnutrition and EED are most prevalent in resource-limited settings where food is limited, and inadequate access to clean water and sanitation results in frequent gastrointestinal pathogen exposures. Even as overt diarrhea rates in these settings decline, silent enteric infections and faltering growth persist. Furthermore, beyond restricted physical growth, EED and/or enteric pathogens also associate with impaired oral vaccine responses, impaired cognitive development, and may even accelerate metabolic syndrome and its cardiovascular consequences. As these potentially costly long-term consequences of early childhood enteric infections increasingly are appreciated, novel therapeutic strategies that reverse damage resulting from nutritional deficiencies and microbial insults in the developing small intestine are needed. Given the inherent limitations in investigating how specific intestinal pathogens directly injure the small intestine in children, animal models provide an affordable and controlled opportunity to elucidate causal sequelae of specific enteric infections, to differentiate consequences of defined nutrient deprivation alone from co-incident enteropathogen insults, and to correlate the resulting gut pathologies with their functional impact during vulnerable early life windows.
环境肠道功能障碍 (EED)（也称为环境肠病）是一种亚临床慢性肠道疾病，是导致儿童早期营养不良的新兴因素。EED 在资源有限的环境中很常见，据推测它由小肠损伤、营养吸收功能障碍和慢性炎症引起，导致儿童早期生长发育受损。尽管人们对环境暴露组中的化学毒素假设潜在的致病作用越来越感兴趣，但已发表数据的倾向，以及本综述的重点，都暗示了环境微生物的关键作用。儿童早期营养不良和 EED 在资源有限的环境中最为普遍，这些环境中食物有限，清洁水和卫生设施不足导致经常发生胃肠道病原体暴露。即使这些环境中明显的腹泻率下降，沉默的肠道感染和生长迟缓仍在持续。此外，除了限制身体生长外，EED 和/或肠道病原体还与口服疫苗反应受损、认知发育受损有关，甚至可能加速代谢综合征及其心血管后果。由于越来越多的人认识到这些早期肠道感染的潜在长期后果，因此需要新的治疗策略来逆转发育中小肠因营养缺乏和微生物侵袭而造成的损害。鉴于在研究特定肠道病原体如何直接损伤儿童小肠方面存在固有局限性，动物模型为阐明特定肠道感染的因果后果提供了一个负担得起且可控的机会，使我们能够区分单纯营养剥夺和同时存在的肠道病原体侵袭的后果，并将由此产生的肠道病理与它们在脆弱的早期生命窗口中的功能影响联系起来。
