Short chain fatty acid-induced colitis in mice.

Short-chain fatty acids (e.g. acetic, propionic and butyric acid) are metabolic products produced by colonic bacteria. Since intra-rectal instillation of dilute acetic acid to rats and cats has been reported to produce a diffuse colitis similar to the human disease, in our study we have investigated the effect of intra-rectal butyric acid in mice. Male BKA mice (n = 6) received 01 ml of dilute butyric acid by intra-rectal instillation which was flushed out with saline after 10 sec. Control animals received saline alone. The severity of observed inflammatory responses was assessed using an arbitrary scoring system based on clinical, macroscopic and histological features of colitis. Colitic oedema was measured as percentage (%) tissue water compared with that in saline controls. The peak oedema response was found to be at around 4 hours. A concentration-dependent symptomatic response was obtained at concentrations between 1% and 12% of butyric acid. Oedema production was similar at all concentrations above 1%. The 3% butyric acid response produced a moderate colitis with mild erythema, oedema, crypt abscess formation, goblet cell depletion and cellular infiltration without total loss of mucosal architecture. The colitogenic action of butyric acid in mouse colon could not be reproduced by low pH alone, nor by the butyrate anion at neutral or alkaline pH. These results indicate that intra-rectal butyric acid induces a consistent and reproducible colitis in mice.