Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively Correlates with Symptoms in Functional Dyspepsia

Tanaka, Fumio; Tominaga, Kazunari; Fujikawa, Yoshiko; Nagami, Yasuaki; Kamata, Noriko; Yamagami, Hirokazu; Tanigawa, Tetsuya; Shiba, Masatsugu; Watanabe, Toshio; Fujiwara, Yasuhiro

doi:10.1007/s10620-016-4329-5

Cited by 34 publications

(43 citation statements)

References 21 publications

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“…80) are upregulated in duodenal biopsy samples of patients with functional dyspepsia. This finding is consistent with higher levels of GDNF in patients with functional dyspepsia 79 . Both duodenal and gastric biopsy samples showed mast cell hyperplasia and an increased release of histamine and tryptase (which indicates mast cell activation) 81 .…”

Section: Gastroduodenal Sensitivitysupporting

confidence: 87%

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Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

261

247

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| Functional dyspepsia is one of the most prevalent functional gastrointestinal disorders. Functional dyspepsia comprises three subtypes with presumed different pathophysiology and aetiology: postprandial distress syndrome (PDS), epigastric pain syndrome (EPS) and a subtype with overlapping PDS and EPS features. Functional dyspepsia symptoms can be caused by disturbed gastric motility (for example, inadequate fundic accommodation or delayed gastric emptying), gastric sensation (for example, sensations associated with hypersensitivity to gas and bloating) or gastric and duodenal inflammation. A genetic predisposition is probable but less evident than in other functional gastrointestinal disorders, such as irritable bowel syndrome (IBS). Psychiatric comorbidity and psychopathological state and trait characteristics could also play a part, although they are not specific to functional dyspepsia and are less pronounced than in IBS. Possible differential diagnoses include Helicobacter pylori infection and peptic ulceration. Pharmacological therapy is mostly based on the subtype of functional dyspepsia, such as prokinetic and fundus-relaxing drugs for PDS and acid-suppressive drugs for EPS, whereas centrally active neuromodulators and herbal drugs play a minor part. Psychotherapy is effective only in a small subset of patients, whereas quality of life can be severely affected in nearly all patients. Future therapies might include novel compounds that attempt to treat the underlying gastric and duodenal inflammation. NATURE REVIEWS | DISEASE PRIMERS VOLUME 3 | ARTICLE NUMBER 17081 | 1 PRIMER © 2 0 1 7 M a c m i l l a n P u b l i s h e r s L i m i t e d , p a r t o f S p r i n g e r N a t u r e . A l l r i g h t s r e s e r v e d .standard therapy for gastro -oesophageal reflux disease. Paediatric dyspeptic symptoms are being addressed in a separate classification effort 10 . This Primer covers functional dyspepsia in adults only, although we sporadically refer to paediatric functional dyspepsia when similarities exist. EpidemiologyThe population prevalence of functional dyspepsia is quite variable across the globe, with overall high numbers (10-40%) in Western countries and low numbers (5-30%) in Asia, independent of the respective functional dyspepsia definitions 11 . A large-scale health and nutrition survey from France 12 (which involved >35,000 people) identified that 15% of individuals had suspected functional dyspepsia, 28% had irritable bowel syndrome (IBS) and 6% had both. The population of patients who are affected by both IBS and functional dyspepsia has been reported to range between 10% and 27% in previous studies 13 and to approach 30% in popu lation samples; it could be even higher in specific populations 14,15 . This observation has given rise to the term 'overlap syndrome' (REF. 13), which calls into question the sensitivity and specificity of the Rome criteria, at least for IBS and functional dyspepsia. This argument is also supported by the observation that patients with functional dyspepsia m...

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Section: Gastroduodenal Sensitivitysupporting

confidence: 87%

“…Evidence for sensitization of peripheral nerves is prov ided by the observation that nociceptor-related genes that encode β-nerve growth factor, glial cell line-derived neurotrophic factor (GDNF) 79 and TRPV1 (REF. 80) are upregulated in duodenal biopsy samples of patients with functional dyspepsia.…”

Section: Gastroduodenal Sensitivitymentioning

confidence: 99%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

261

247

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“…Of the 10 studies that evaluated mast cell counts, 5 studies reported increased mast cell infiltration in the duodenum and 1 in the duodenal bulb. The pooled results showed increased duodenal mast cell counts (SMD = 0.66, 95%CI 0.20‐1.13, P = .005) in individuals with FD . There was heterogeneity observed among the studies ( I 2 = 82%, P < .001) but no publication bias was detected (Egger's test P = .833).…”

Section: Resultsmentioning

confidence: 88%

“…Nineteen studies examined eosinophil infiltration in FD. A pooled evaluation showed increased duodenal eosinophils in individuals with FD (SMD = 0.95, 95%CI 0.66‐1.24, P < .001) compared to controls (Figure A) . Although significant heterogeneity ( I 2 = 88%, P < .001) and publication bias (Egger's test P = .004, Figure B) were observed, no single publication was found to bias the results in the sensitivity analysis (Figure C).…”

Section: Resultsmentioning

confidence: 94%

“…A previous study showed that abnormal nerve function observed in FD is associated with increased duodenal eosinophils and mast cells . Others reported that enteric glial cells, co‐localized with eosinophils and mast cells, are associated with neural depolarization and long‐term excitation in FD . A variety of chemical mediators released by inflammatory cells including 5‐HT, histamine, substance P, and cytokines are crucial in regulating gastrointestinal motility and sensation through specific receptors that are widely expressed in primary afferent neurons and nerve fibers …”

Section: Discussionmentioning

confidence: 99%

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Micro‐inflammation in functional dyspepsia: A systematic review and meta‐analysis

Chen

Kim

et al. 2018

Neurogastroenterology Motil

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Functional dyspepsia (FD) is a gastrointestinal disorder of unknown etiology. Although micro-inflammation appears to be important in the pathogenesis, studies evaluating immune activation in FD have been inconsistent. A systematic review of literature and meta-analysis was performed to compare immunologic cell counts and cytokine levels in the mucosa and peripheral blood of individuals with FD and healthy controls. PubMed, Embase, and the Cochrane library were searched. Data on immunologic cell counts and cytokines levels among individuals with FD and control groups were extracted and compared by calculating standard mean differences (SMD). Thirty-seven studies met the inclusion criteria. Mast cell (SMD = 0.94, 95%CI 0.26-1.62, P = .007) and eosinophil counts (SMD = 0.36, 95%CI 0.06-0.68, P = .03) in the stomach were increased, among individuals with FD compared to controls. Similarly, mast cell (SMD = 0.66, 95%CI 0.20-1.13, P = 0.005) and eosinophil (SMD = 0.95, 95%CI 0.66-1.24; P < .001) counts in the duodenum were also increased in those with FD compared to controls. In a subgroup analysis, elevated eosinophil counts in the duodenum were observed in both post-prandial distress syndrome (SMD = 0.97, 95%CI 0.46-1.47, P = .0002) and epigastric pain syndrome subtypes (SMD = 1.16, 95%CI 0.48-1.83, P = .0008). No differences in mucosal intraepithelial lymphocyte, enterochromaffin cell, and neutrophil counts, as well as, peripheral interlukin-6 (IL-6) and IL-10 levels were observed among individuals with FD and controls. Micro-inflammation in the form of local immune cell infiltration, particularly eosinophils and mast cells, characterizes the pathogenesis of FD.

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Correlation between anxiety and decreased quality of life in patients with non‐esophageal eosinophilic gastrointestinal diseases

Tanaka,

Kanamori,

Sawada

et al. 2023

JGH Open

Self Cite

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Background and AimMental status such as anxiety and depression in patients with non‐esophageal eosinophilic gastrointestinal diseases (non‐EoE EGIDs) has not been studied. The aim of this study was to evaluate whether patients with non‐EoE EGIDs had mental disorders and decreased mental‐health‐related quality of life (QOL) similar to those in patients with disorders of gut–brain interaction (DGBI).MethodsWe enrolled patients with non‐EoE EGIDs and DGBI visiting the Osaka Metropolitan University Hospital, and the measures listed below were compared between the groups. We collected data using the following questionnaires: hospital anxiety and depression scale, and short form (SF)‐8 including mental component summary (MCS)‐8.ResultsWe evaluated 21 and 17 patients with non‐EoE EGIDs and DGBI, respectively. The anxiety score was not significantly different between the groups. The proportion of patients with possible anxiety was not significantly different between the groups (19.0% vs 33.3%). These results show that patients with non‐EoE EGIDs had anxiety that might be equivalent to that of patients with DGBI. The depression score and proportion of patients with possible depression in the non‐EoE EGID group tended to be lower than those in the DGBI group. MCS‐8 scores were not significantly different between the non‐EoE EGID and DGBI groups, which might imply an equivalent decrease in mental‐health‐related QOL in both groups of patients. In patients with non‐EoE EGIDs, the anxiety score had a significant inverse association with the MCS‐8 score.ConclusionsPatients with non‐EoE EGIDs may have anxiety that correlates with decreased mental‐health‐related QOL.

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Concentration of Glial Cell Line-Derived Neurotrophic Factor Positively Correlates with Symptoms in Functional Dyspepsia

Abstract: Increased expression of duodenal GDNF might be involved in FD pathophysiology and symptom perception.

Cited by 34 publications

References 21 publications

Functional dyspepsia

Functional dyspepsia

Micro‐inflammation in functional dyspepsia: A systematic review and meta‐analysis

Correlation between anxiety and decreased quality of life in patients with non‐esophageal eosinophilic gastrointestinal diseases

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