ABSTRACT. Environmental enteric dysfunction (EED) is a subclinical enteropathy prevalent in resource-limited settings, hypothesized to be a consequence of chronic exposure to environmental enteropathogens, resulting in malnutrition, growth failure, neurocognitive delays, and oral vaccine failure. This study explored the duodenal and colonic tissues of children with EED, celiac disease, and other enteropathies using quantitative mucosal morphometry, histopathologic scoring indices, and machine learning–based image analysis from archival and prospective cohorts of children from Pakistan and the United States. We observed villus blunting as being more prominent in celiac disease than in EED, as shorter lengths of villi were observed in patients with celiac disease from Pakistan than in those from the United States, with median (interquartile range) lengths of 81 (73, 127) µm and 209 (188, 266) µm, respectively. Additionally, per the Marsh scoring method, celiac disease histologic severity was increased in the cohorts from Pakistan. Goblet cell depletion and increased intraepithelial lymphocytes were features of EED and celiac disease. Interestingly, the rectal tissue from cases with EED showed increased mononuclear inflammatory cells and intraepithelial lymphocytes in the crypts compared with controls. Increased neutrophils in the rectal crypt epithelium were also significantly associated with increased EED histologic severity scores in duodenal tissue. We observed an overlap between diseased and healthy duodenal tissue upon leveraging machine learning image analysis. We conclude that EED comprises a spectrum of inflammation in the duodenum, as previously described, and the rectal mucosa, warranting the examination of both anatomic regions in our efforts to understand and manage EED.

中文翻译：

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定量形态测量和机器学习模型探索环境肠道功能障碍儿童的十二指肠和直肠粘膜组织

摘要。环境性肠功能障碍（EED）是一种在资源有限的环境中普遍存在的亚临床肠病，推测是长期暴露于环境肠病原体的结果，导致营养不良、生长障碍、神经认知延迟和口服疫苗失败。本研究利用定量粘膜形态测量、组织病理学评分指数以及来自巴基斯坦和美国儿童档案和前瞻性队列的基于机器学习的图像分析，探讨了患有 EED、乳糜泻和其他肠病的儿童的十二指肠和结肠组织。我们观察到，绒毛变钝在乳糜泻中比在 EED 中更为突出，因为观察到来自巴基斯坦的乳糜泻患者的绒毛长度比来自美国的患者短，中位（四分位距）长度为 81 (73, 127 ) µm 和 209 (188, 266) µm 分别。此外，根据马什评分方法，巴基斯坦队列中乳糜泻的组织学严重程度有所增加。杯状细胞耗竭和上皮内淋巴细胞增加是 EED 和乳糜泻的特征。有趣的是，与对照组相比，EED 病例的直肠组织显示隐窝中的单核炎症细胞和上皮内淋巴细胞增加。直肠隐窝上皮中中性粒细胞的增加也与十二指肠组织中 EED 组织学严重程度评分的增加显着相关。我们利用机器学习图像分析观察到患病和健康十二指肠组织之间的重叠。我们的结论是，如前所述，EED 包括十二指肠和直肠粘膜的一系列炎症，因此在我们努力了解和管理 EED 的过程中需要对这两个解剖区域进行检查。