Short-chain fatty acids induce colonic mucosal injury in rats with various postnatal ages.

Short chain fatty acids (SCFAs) may play a role in the pathogenesis of neonatal necrotizing enterocolitis. To evaluate the injurious effect of SCFAs on the colonic mucosa of rats at various postnatal developmental stages, we studied a total of 170 newborn Sprague-Dawley rats at postnatal ages days 3, 9, and 23. A 1.8-F silastic catheter or umbilical catheter was inserted rectally deep into the proximal colon of the rats. Rats from each of the three postnatal age groups were randomly divided to receive one of the following distinct SCFA solutions: acetic acid, butyric acid, propionic acid, or a mixture of above SCFAs solutions. An additional subgroup of rats from each of the age groups received normal saline as a control. The concentration of each SCFA solution was 300 mM, and the pH of all solutions was adjusted to 4.0. The volume of administered solution was 0.1 mL/10 g of body weight. After 24 h, all rats were killed and the daily weight change was recorded and proximal colon was collected for histologic examination. A histologic injury score was used to quantify the severity of mucosal injury. The severity of mucosal injury induced by luminal SCFAs administration decreased as the rats matured; by postnatal day 23, the injury caused by SCFAs was minimal. Thus, the severity of the colonic mucosal injury induced by luminal SCFAs is maturation dependent; the immature state of the mucosal defense in early postnatal age in newborn rat may explain its greater vulnerability to luminal SCFAs.