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. 2022 Apr 26;16:831761. doi: 10.3389/fnins.2022.831761

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.