TABLE 2.
Impaired duodenal mucosal permeability in adult Functional Dyspepsia patients.
| Findings | Methods | Population | Trial details | |
| In vivo permeability | ||||
| ↑LMR (60–120 min) | ∼↑Fd4 | HPLC-MS | 39 NUD (16 on-PPI) vs. 24 controls | United States, 2021 (Puthanmadhom Narayanan et al., 2021b) |
| ↑Mucosal admittance | tissue conductance | 21 FD (Rome III, 17 on-PPI) vs. 23 controls | Japan, 2017 (Ishigami et al., 2017) | |
| ↓Mucosal impedance | ∼↓ZO1, IL-1β | tissue conductance | 24 FD (Rome III, 12 on-PPI) vs. 20 controls (1 on-PPI) | Japan, 2019 (Komori et al., 2019) |
| ↓Baseline impedance | HRM/Z | 16 FD (Rome IV, 1 Hp-positive) vs. 15 controls | United Kingdom, 2020 (Nakagawa et al., 2020) | |
| ↑Epithelial gap density (D3) | CLE | 14 FD (Rome IV, 3 on-PPI) vs. 8 controls | United States, 2020 (Nojkov et al., 2020) | |
| Ex vivo permeability | ||||
| ↑Isc (resting and stimulated) | Ussing chambers | 37 NUD (30 Rome III, 15 on-PPI) vs. 20 controls | United States, 2021 (Puthanmadhom Narayanan et al., 2021a) | |
| ↑Fd4-passage, ↓TEER | Ussing chambers | 15 FD (Rome III, 6 on-PPI) vs. 15 controls | Belgium, 2014 (Vanheel et al., 2014) | |
| ↑Fd4-passage, ↓bacterial passage | Ussing chambers | FD | Belgium, 2020 (Beeckmans et al., 2020) | |
| ↓TEER | ∼ Abdominal pain, bloating, IFNγ | Ussing chambers | 10 FD (Rome IV, 3 on-PPI) vs. 10 controls (globus/IDA, 4 on-PPI) | United States, 2020 (Nojkov et al., 2020) |
| ↑Fd4-passage | Ussing chambers | 28 FD (Rome IV) vs. 30 controls | Belgium, 2021 (Wauters et al., 2021b) | |
| Non-functional assessment | ||||
| ↓ZO1 (protein) ↓OCLN (RNA, protein), p-OCLN (protein) ↓β-catenin (RNA, protein), E-cadherin (protein) ↓DSC2 (RNA), DSG2 (RNA, protein) |
p-OCLN ∼ ↑eosinophils, ↑mast cells, ↓TEER E-cadherin ∼ ↑mast cells, ↑eosinophils, ↑Fd4 |
qPCR, WB, IF | 15 FD (Rome III, 6 on-PPI) vs. 15 controls | Belgium, 2014 (Vanheel et al., 2014) |
| ↓ZO1 (RNA) | ∼↓Impedance | qPCR | 24 FD (Rome III) vs. 20 controls | Japan, 2019 (Komori et al., 2019) |
| ↓CLDN1 (RNA) | qPCR | 10 FD (Rome IV, 3 on-PPI) vs. 10 controls (globus/IDA, 4 on-PPI) | United States, 2020 (Nojkov et al., 2020) | |
| ↓CLDN1 (protein) | IHC | 9 FD (Rome III) vs. 9 controls | China, 2018 (Du et al., 2018) | |
| ↑CLDN3 (RNA) | qPCR | 35 FD (Rome III, 7 Hp-positive) vs. 31 controls (3 Hp-positive) | Japan, 2019 (Taki et al., 2019) | |
| ↓ZO1, OCLN, CLDN12, CLDN18 ↓E-cadherin, p120 catenin, nectin-3 ↓DSG2, DSC2, plakophilin-2, plakoglobin ↓/↑ regulatory miRNAs |
RNA-seq | 39 NUD (32 Rome III, 16 on-PPI) vs. 21 controls | United States, 2021 (Puthanmadhom Narayanan et al., 2021b) | |
| ↓Junctions with perijunctional condensation | Intercellular distance and intercellular distance ∼Fd4-passage, ZO2/3 junctions with perijunctional condensation ∼ZO2 |
TEM | 37 NUD (32 Rome III, 16 on-PPI) vs. 21 controls | United States, 2021 (Puthanmadhom Narayanan et al., 2021b) |
| ↑Intercellular paracellular distance (adherens junction) | ∼Postprandial fullness, early satiety | TEM | 9 FD (Rome III) vs. 5 controls (1 Hp-positive) | Japan, 2016 (Tanaka et al., 2016) |
| ↑Pyroptosis (caspase-1) | IHC | 14 FD (Rome IV, 3 on-PPI) vs. 6 controls (globus/IDA, 4 on-PPI) | United States, 2020 (Nojkov et al., 2020) |
CLDN, claudin; CLE, confocal laser endomicroscopy; DIS, dilated intercellular spaces; DSC, desmocollin; DSG, desmoglein; Fd4, fluorescein isothiocyanate-labeled 4 kDa dextran; Hp, Helicobacter pylori; HPLC-MS, high-performance liquid chromatography-mass spectrometry; HRM/Z, high-resolution manometry impedance; IDA, iron deficiency anemia; IF, immuno-fluorescence; IFN, interferon; IHC, immuno-histochemistry; IL, interleukin; Isc, short-circuit current; NUD, non-ulcer dyspepsia; OCLN, occludin; PPI, proton pump inhibitor; qPCR, quantitative PCR; TEER, transepithelial electrical resistance; TEM, transmission electron microscopy; WB, Western blot; ZO, zonula-occludens. ∼ for correlation, underlined text for significant changes after correction for multiple testing.