Cecal infusion of butyrate increases intestinal cell proliferation in piglets

The effects of colon-derived butyrate on intestinal cell proliferation are controversial. In vitro studies suggest an inhibitory effect, and in vivo studies suggest the opposite, but neither type of study has been based on a physiologically relevant, intracolonic supply of butyrate. In this study, piglets (n = 24) were fed sow's milk replacement formula and randomized into 4 equal groups: 1) control; 2) cecal butyrate infusion at a rate equal to that produced in the colon; 3) inulin supplementation at a concentration previously found to lower cecal cell proliferation; and 4) butyrate infusion plus inulin supplementation. After 6 d of oral feeding, cecal butyrate infusions were initiated for a period of 4 d. Cecal, distal colonic, jejunal, and ileal cell proliferation, apoptosis, and morphology were evaluated and serum concentration of glucagon-like peptide-2 (GLP-2) was measured. Butyrate or inulin did not affect GLP-2, weight gain, apoptosis, intestinal injury scores, cecal or colon crypt depth, and jejunal or ileal villus height. For cell proliferation, there was a significant interaction between inulin, butyrate, and tissue (P = 0.007). Inulin modified the effect of butyrate (butyrate x inulin interaction in cecum, P = 0.001; in distal colon, P = 0.018; in ileum, P = 0.001; and in jejunum, P = 0.003). In the absence of inulin, butyrate caused a 78- 119% increase in cell proliferation in the ileum, distal colon, jejunum, and cecum (P < or = 0.002). Thus, at an entry rate into the colon within the physiological range, butyrate caused increased intestinal cell proliferation, but inulin tended to block this effect. Thus, intracolonic butyrate may enhance intestinal growth during infancy.