Evidence for neuronal and structural changes in submucous ganglia of patients with functional dyspepsia

Am J Gastroenterol. 2015 Aug;110(8):1205-15. doi: 10.1038/ajg.2015.158. Epub 2015 Jun 16.


Objectives: An intact and well-functioning enteric nervous system is necessary to efficiently organize gut function. Functional gastrointestinal disorders are pathological entities in which gut function is impaired without a clearly established pathophysiology. On the basis of the relative ease with which intestinal biopsies can be obtained, and taking advantage of a recently developed optical recording technique, we evaluated whether functional neuronal defects exist in enteric nerves of patients with functional dyspepsia (FD).

Methods: The submucous plexus isolated from duodenal biopsies taken from FD patients and control subjects was used to functionally and morphologically examine nerves and ganglionic architecture (neurons and glial cells). In light of previous studies reporting eosinophil and mast cell infiltration in the gut mucosa of FD patients, we also examined whether these cells infiltrated the submucous plexus and whether this correlated with neuronal activity and specific clinical symptoms.

Results: We demonstrate that neuronal functioning is impaired in the submucous plexus of FD patients, as shown by decreased calcium responses to depolarization and electrical stimulation. Glial (S100) and neuronal (HuCD) markers show signs of gliosis, altered ganglionic architecture, and neuronal abnormalities in the submucous plexus of FD patients. We found that eosinophils and mast cells infiltrated the submucous layer of FD patients to a much larger extent than in controls. A significant correlation was found between the number of these cells and the calcium transient amplitudes measured in submucous ganglia.

Conclusions: We provide the first direct evidence that FD is characterized by functional and structural abnormalities within the submucous ganglion plexus, which may be of future predictive and diagnostic value in the treatment of FD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biopsy
  • Calcium / metabolism
  • Case-Control Studies
  • Dyspepsia / etiology
  • Dyspepsia / metabolism
  • Dyspepsia / pathology*
  • Eosinophils
  • Female
  • Gliosis / pathology*
  • Humans
  • Leukocyte Count
  • Male
  • Mast Cells
  • Middle Aged
  • Neuroglia / chemistry
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Neurons / chemistry
  • Neurons / metabolism
  • Neurons / pathology
  • S100 Proteins / analysis
  • Submucous Plexus / chemistry
  • Submucous Plexus / metabolism
  • Submucous Plexus / pathology*
  • Young Adult


  • S100 Proteins
  • Calcium