TABLE 2.
Evidence for immune activation in functional dyspepsia at the molecular level.
| Findings | Associations | Methods | Population | Study details |
| Duodenal mucosal immune activation | ||||
| ↑ iNOS | ∼ mast cell degranulation and abdominal distention | IHC | 48 FD (Rome III) vs. 21 HC | China, 2015 (Yuan et al., 2015a) |
| ↑ GDNF | ∼ epigastric burning | ELISA | 9 FD (Rome III) vs. 5 HC | Japan, 2016 (Tanaka et al., 2016) |
| ↑ IL-1β | ∼↓ duodenal mucosal impedance (↑permeability) | qPCR | 24 FD (Rome III) vs. 20 HC | Japan, 2019 (Komori et al., 2019) |
| ↑ IL-6 | ∼ TJ gene expression | qPCR | 18 FD (Rome IV) vs. 20 HC | United States, 2020 (Nojkov et al., 2020) |
| Gastric mucosal immune activation | ||||
| ↑ Histamine, ↑ 5-HT and ↑ tryptase | ELISA, HPLC, western blot | 30 presumed pi FD (Rome III) vs. 20 HC | China, 2010 (Li et al., 2010) | |
| ↑ NGF, ↑ GDNF and ↑ TRPV1 | ∼ epigastric pain/burning and postprandial fullness | qPCR, IHC | 117 FD (Rome III) vs. 55 HC | South Korea, 2016 (Choi et al., 2016) |
| ↓ BDNF, ↑ TRPV1 and -2 | qPCR | 36 PDS (Rome IV) vs. 23 HC | China, 2018 (Cheung et al., 2018) | |
| IL-6 | ∼ epigastric burning | |||
| Systemic immune activation | ||||
| ↑ IL-5, ↑ IL-13 and ↓ IL-10 (stimulated) | ELISA (stimulated PBMC culture supernatants) | 23 FD (Rome II) vs. 32 HC | Belgium, 2009 (Kindt et al., 2009b) | |
| ↓ IL-12 (stimulated) | ELISA (stimulated monocyte culture supernatants) | 23 FD (Rome II) vs. 32 HC | Belgium, 2009 (Kindt et al., 2009b) | |
| ↑ TNF-α, ↑ IL-1β and ↑ IL-10 | ∼ GI symptoms and gastric emptying | ELISA (PBMC culture supernatants) | 45 FD (Rome II) vs. 35 HC | Australia, 2011 (Liebregts et al., 2011) |
| ↓ BDNF and ↓ MCP-1 | ELISA and multiplex | 36 PDS (Rome IV) vs. 23 HC | China, 2018 (Cheung et al., 2018) | |
| Peripheral cytokines | ∼ FD and GI symptoms | |||
| ↑ anti-CdtB antibodies | ELISA | 61 FD (Rome III) vs. 245 HC | Australia, 2019 (Talley et al., 2019) | |
| ↑ hs-CRP | Turbidimetry | 28 FD (Rome IV) vs. 30 HC | Belgium, 2021 (Wauters et al., 2021a) | |
iNOS: inducible nitric oxide synthase, IHC: immunohistochemistry, FD: functional dyspepsia, HC: healthy control, GDNF: glial cell-derived neurotrophic factor, ELISA: enzyme-linked immunosorbent assay, IL: interleukin, qPCR: quantitative polymerase chain reaction, 5-HT: serotonin, HPLC: high-performance liquid chromatography, pi: post-infectious, NGF: nerve growth factor, TRPV: transient receptor potential vanilloid, BDNF: brain-derived neurotrophic factor, PDS: postprandial distress syndrome, PBMC: peripheral blood mononuclear cells, TNF: tumor necrosis factor, GI: gastrointestinal, MCP: monocyte chemoattractant protein, CdtB: cytolethal distending toxin B, hs-CRP: high-sensitivity C-reactive protein.