Evidence for Neuronal and Structural Changes in Submucous Ganglia of Patients With Functional Dyspepsia

Cirillo, Carla; Bessissow, Talat; Desmet, An-Sofie; Vanheel, Hanne; Tack, Jan; Berghe, Pieter Vanden

doi:10.1038/ajg.2015.158

Cited by 138 publications

(146 citation statements)

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“…Duodenal eosinophilia occurs in paediatric 90 and adult functional dyspepsia 91 and is probably linked to abnormal submucosal nerve structure and impaired responsiveness of submucosal neurons 92 . Eosinophils and mast cells that degranulate next to enteric neurons provide a mechanism for sensory excitation, which can be perceived by the enteric and central nervous systems 54 .…”

Section: Gastroduodenal Inflammationmentioning

confidence: 99%

“…Increased CD4 + T helper 2 (T H 2) cell response is a potent producer of key cytokines (IL-4, IL-5 and IL-13) that are involved in recruiting and activating eosinophils and mast cells 97 . Eosinophil and mast cell numbers are increased in the submucosal plexus of the duodenum in patients with functional dyspepsia, and this finding was accompanied by a clear impairment of nerve excitability in the duodenal submucosal plexus -a decreased calcium response to depolarization and electrical stimulation -and could also implicate the central nervous system 54,92 . Blood-borne cytokines from the gut can also signal in the brain, thereby enabling cross-talk between the immune system, brain and gut 54 .…”

Section: Gastroduodenal Inflammationmentioning

confidence: 99%

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Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

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260

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 Inflammationmentioning

confidence: 99%

Section: Gastroduodenal Inflammationmentioning

confidence: 99%

Functional dyspepsia

Enck¹,

Azpiroz

Boeckxstaens

et al. 2017

Nat Rev Dis Primers

Self Cite

260

247

View full text Add to dashboard Cite

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“…In a recent study, 5 patients with Los Angeles Grade C oesophagitis were given proton pump inhibitors (PPIs). Oesophageal biopsies were evaluated using a 0-3 scale for epithelial inflammation, basal cell and papillary hyperplasia, and spongiosis.…”

Section: Acknowledgementmentioning

confidence: 99%

Editorial: the diminishing returns of normalisation of the oesophageal mucosa

Genta¹

2017

Aliment Pharmacol Ther

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hampered by the lack of correlation between symptom improvement and changes in physiologic measures such as gastric emptying studies.A new direction in functional dyspepsia is the concept that the duodenum may be the source of symptoms. Observational studies show an increased number of eosinophils in duodenal biopsies obtained from adults and children with functional dyspepsia. [2][3][4] Other studies have shown an increase in mast cells in the mucosa and evidence of inflammation in the sub-mucosal nerves and ganglia in the upper gastrointestinal tract. 5An inflammatory reaction may trigger the accumulation of eosinophils in the duodenal mucosa. The trigger may be intrinsic through the brain-gut axis or extrinsic through ingested proteins or bacteria.During the inflammatory process, a number of cytokines are released and activate the eosinophils, which are then ready for degranulation.During the process of degranulation, nerve growth factor is released and may have an effect on the sensory nerves of the upper gastrointestinal tract. Other products of degranulation such as major basic proteins can affect smooth muscle function causing spasm. Studies have shown that children with atopy have duodenal eosinophilia and that challenge with cow's milk protein can generate dyspeptic symptoms. 6 Other studies have shown that inflammation, including eosinophilia, may be seen in patients with Helicobacter pylori infection. 7 The process by which extrinsic factors create duodenal eosinophilic infiltration is uncertain. One plausible postulate is that alterations in mucosal permeability allow food-based antigens and bacterial products exposure to the immune system. What are the implications for future treatments? Anti-inflammatory agents and drugs aimed at decreasing allergic reactions are already being studied in functional dyspepsia. 9,10 Observational studies, while confirming the original observation of duodenal eosinophilia, need to give way to mechanistic studies that help us understand the pathogenesis of duodenal eosinophilia. Future studies will help determine if treating the eosinophilia, much as we treat eosinophilic oesophagitis, or restricting the diet will alleviate dyspeptic symptoms. ACKNOWLEDGEMENTDeclaration of personal interests: Consultant Ironwood Pharmaceuticals.

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“…Functional dyspepsia according to the Rome IV diagnostic criteria [4] comprises postprandial distress syndrome (bothersome postprandial fullness or early satiety severe enough to impact on regular activities for 3 or more days per week in the past 3 months) or the epigastric pain syndrome (bothersome epigastric pain or epigastric burning 1 or more days per week in the past 3 months), although many patients complain of both syndromes [4]. Recent evidence has identified duodenal inflammation in functional dyspepsia, with a small but significant increase in eosinophils in the duodenal mucosa (and in some cases mast cells), most notably in subjects with early satiety and postprandial distress [5,6].…”

mentioning

confidence: 99%

“…Histamine 2 receptor antagonists (H 2 RAs), a small portion of claims implicating acid suppression, were mostly associated with concerns of limited or absent efficacy, or a false-positive drug screen. A meta-analysis based on older studies suggested that H 2 RA therapy is efficacious in functional dyspepsia [21], of interest as more recently duodenal eosinophilia and increased mast cells (that may release histamine) [5,6] or duodenal changes in the microbiome that might release excess histamine [22] suggest that antagonizing histamine might do more good than just reduce gastric acid secretion [1]. Histamine antagonism may thus be an alternative therapy in functional dyspepsia with equal efficacy and lower risk of adverse events than with other drugs.…”

mentioning

confidence: 99%