Short-Chain Fatty Acids Affect Hirschsprung Associated Enterocolitis

Background: Hirschsprung associated enterocolitis (HAEC) is a common complication of Hirschsprung's disease (HD), with high morbidity and mortality. Short-chain fatty acids (SCFAs) have been shown to play a role in maintaining intestinal integrity, and regulating the immune system, inflammatory response, and lipid metabolism. This study explored the SCFAs in HD and HAEC and their possible underlying mechanism. Methods: Ednrb-/- (Targeted-null mouse) mice were selectively bred and fed until 2-weeks old and 3-weeks old as HD model and HAEC model mice, respectively; the mouse genotypes were identified by polymerase chain reaction (PCR). Hematoxylineosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), immunofluorescence, and immunohistochemistry were used to assess histopathological damage, interleukin (IL)-6 levels, intestinal barrier dysfunction (ZO-1, E-cadherin and occludin), and apoptosis (Bax and caspase-3). The level of G-protein-coupled receptor 43 in colon tissue was measured by Western blotting. The content of SCFAs in the feces of the mice was evaluated by gas chromatography-mass spectrometer (GC-MS). Results: Integrated colon tissue with clear structure was observed in the "2-week-old" and "3-week-old" control groups. In HD mice, intermuscular layer tissue was hypertrophic with suspected hypertrophic plexus structures. In HAEC mice, disordered intestinal gland structure was observed, with hypertrophic intermuscular layer. The serum level of interleukin-6 (IL-6) in HAEC mice was much higher than that of controls (p < 0.01). ZO-1 and E-cadherin were mainly expressed in Galeati's glands. ZO-1 (p < 0.01) and E-cadherin (p < 0.05) were significantly lower in HD and HEAC mice than in corresponding controls. Bax and caspase-3 levels were extremely low in HD and HEAC mice, with a reduced occludin level (p< 0.01). Moreover, remarkedly down-regulated G-protein-coupled receptor 43 (GPCR43) protein levels were observed in HD and HEAC mice (p< 0.01). Furthermore, n-propylacetate and propanoic acid were markedly lower in HD mice compared with those in controls. Conclusion: SCFAs might play a protective role in colon tissue structure by regulating occludin to enhance the barrier function of intestinal epithelium.