Intestinal epithelial barrier and neuromuscular compartment in health and disease

Table 1 Summary of current human and experimental data on molecular, morphological and functional changes in intestinal epithelial barrier and neuromuscular compartment in digestive disorders

Digestive disorder	Morphofunctional changes in intestinal epithelial barrier	Morphofunctional changes in enteric neuromuscular compartment	Notes	Ref.
Human investigations
IBD	Altered composition of mucus layer	↓ Myenteric neurons (b)	(a) UC ↓ claudin-1 and -4; CD ↓ claudin-3, -5 and -8	[5,16-19,23-26,29-36]
	Abnormal glycosylation of mucins	↑ SP release (c)	(b) Another study reported an increment of the enteric neuron number
	↑ Paracellular and transcellular permeability	↑ NK-1 and NK-2 receptors
	↑ Claudin-2 and claudin-18 (a)	Altered morphology of ICC	(c) Other authors reported a significant reduction of both AChE activity and ACh release in IBD patients suffering from moderate-severe disease, as compared with healthy controls or IBD patients with low disease severity
	↓ Occludin and ZO-1	Functional alterations of EGCs
IBS	↑ Mucus secretion	↓ Thickness of muscle layer	(d) Positive correlation between increased intestinal permeability and visceral pain	[51,54-63]
	↑ Paracellular permeability (d)	↑ Entero-endocrine cell activity
	↓ Occludin and ZO-1	↑ SP release (f)
	Altered expression of claudins (e)	Altered circulating levels of 5-HT	(e) IBS-D: ↓ claudin-1 and claudin-4, resulting in diarrhea; IBS-C: ↑ claudin-1, claudin-3 and claudin-4, resulting in constipation
		Altered number and morphology of ICC	(f) Positive correlation between increased SP release and pain scores
		↑ EGC density
Intestinal infections	Altered composition of mucus layer	↓ Circulating levels of 5-HT		[72,74,75,76,78,79]
	↓ Goblet cell number	↑ SP release
	↑ Paracellular permeability altered TJs
	↑ Epithelial apoptosis
Diverticulosis and diverticulitis	↑ Mucosal folds	Altered smooth muscle cells	(g) A more recent study did not observe alterations of ENS	[77,80-83]
	Mucosal ulcerations	Altered serotonergic system
	Crypt distortion	↑ Tachykinergic contractile activity
		↓ Cholinergic pathway activity
		↓ ICC number
		↓ EGC density (g)
Experimental models
IBD	Altered composition of mucus layer	↓ Myenteric neurons		[37-50]
	↓ Goblet cell number	Altered morphology of ICC
	↑ Paracellular and transcellular permeability	↓ EGC density
	↑ Claudin-1 and claudin-2
	↓ Occludin and ZO-1
IBS	↑ Mucus secretion	↓ Thickness of muscle layer	(h) Positive correlation between increased intestinal permeability and visceral pain	[63,65-68,70]
	↑ Paracellular permeability (h)	Altered number of ICC
	↓ Occludin and ZO-1	↑ SP release
		↓ Circulating levels of 5-HT
		↑ EGC density
Intestinal infections	↑ MUC1 expression	↑ SP release		[84-87]
	↓ MUC2 expression
	↑ Paracellular permeability
	Altered TJs

↑: Increase; ↓: Decrease; 5-HT: Serotonin; Ach: Acetylcholine; AChE: Acetylcholinesterase; CD: Crohn’s disease; EGCs: Enteric glial cells; ENS: Enteric nervous system; IBD: Inflammatory bowel disease; IBS: Irritable bowel syndrome; IBS-C: IBS with constipation; IBS-D: IBS with diarrhea; ICC: Interstitial cells of Cajal; MUC: Mucin; NK: Neurokinin; SP: Substance P; TJ: Tight junction; UC: Ulcerative colitis; ZO-1: Zonulin-1.