Histology of the Upper Gastrointestinal Tract, Morphometry and Lymphocyte Subpopulations of the Duodenal Mucosa: Insights from Healthy Individuals

The upper oesophagogastrointestinal (UEGI) tract histology, intestinal morphometry and lymphocyte subpopulations of healthy people is scarcely known. In research studies of inflammation involving the UEGI tract, there is a lack of adequate healthy controls. Aims: To evaluate the histology of the UEGI tract and the duodenal lymphocyte subpopulations of healthy volunteers and patients with gastroesophageal reflux disease (GERD), the latter to assess if it could replace healthy subjects. Healthy individuals were excluded if they had symptoms, comorbidities, pregnancy, toxics, medications or abnormal blood analysis. Subjects in both groups with abnormal duodenal intraepithelial lymphocyte (IEL) counts were also excluded. A total of 280 subjects were assessed, and 37 were included (23 healthy and 14 with GERD). The GERD group showed a higher IEL count (median [IQR]: 19.5 [17-22]), than healthy group: (15 [12-18]), <i>p</i> = 0.004. Eosinophils, mast cells and intestinal morphometry were similar in both groups. In the lamina propria, CD4+ T cells decreased (<i>p</i> = 0.008), and CD8+ T cells increased (<i>p</i> = 0.014). The total innate lymphoid cells (ILC) and CD3- cells decreased (<i>p</i> = 0.007) in GERD group compared to healthy controls. At the intraepithelial level, NKT cells increased (<i>p</i> = 0.036) and ILC3 decreased (<i>p</i> = 0.049) in the GERD group. This is the first study to comprehensively map the histology, morphometry and duodenal subpopulations of healthy volunteers to help define a "gold standard" of normality. The differences found between both groups suggest that, whenever possible, healthy subjects should be included in research studies. Alternatively, we can consider a well-defined homogenous group with GERD to serve as the control group.