Quantitative Morphometry and Machine Learning Model to Explore Duodenal and Rectal Mucosal Tissue of Children with Environmental Enteric Dysfunction

Marium Khan, Zehra Jamil, Lubaina Ehsan, Fatima Zulqarnain, Sanjana Srivastava, Saman Siddiqui, Philip Fernandes, Muhammad Raghib, Saurav Sengupta, Zia Mujahid, Zubair Ahmed, Romana Idrees, Sheraz Ahmed, Fayaz Umrani, Najeeha Iqbal, Christopher Moskaluk, Shyam Raghavan, Lin Cheng, Sean Moore, Syed Asad AliJunaid Iqbal, Sana Syed

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


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.

Original languageEnglish
Pages (from-to)672-683
Number of pages12
JournalAmerican Journal of Tropical Medicine and Hygiene
Issue number4
Publication statusPublished - 5 Apr 2023


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