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Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions

Increased Colonic Luminal Synthesis of Butyric Acid Is Associated with Lowered Colonic Cell Proliferation in Piglets^1,2

C. Lawrence Kien^*,,3, Mary Schmitz-Brown^*, Travis Solley^*, Dayong Sun^** and Wendy L. Frankel

^* Department of Pediatrics, University of Texas Medical Branch, Department of Pediatrics and ^** Department of Surgery, Shriners Hospital for Children, Galveston, TX, and the Department of Pathology, The Ohio State University College of Medicine and Public Health, Columbus, OH

³ To whom correspondence should be addressed. E-mail: cl.kien{at}uvm.edu.

ABSTRACT

Butyrate inhibits colonic cell proliferation in vitro but reportedly has an opposite effect in vivo. Because lactulose feeding decreases cecal cell proliferation, an effect attenuated by prefeeding inulin, we hypothesized that lactulose feeding would decrease colonic luminal synthesis of butyrate, and that prefeeding and cofeeding inulin would prevent this effect. Piglets (n = 31) were catheterized and randomly assigned to 1 of 4 groups: Control formula (C); control formula + lactulose (L); control formula + lactulose + inulin (L + I); and control formula + inulin (I). At 6 and 7 d postsurgery, the rate of cecal synthesis of butyrate, cecal cell proliferation and apoptosis, and cecal and distal colon butyrate concentration were measured. In groups C, L, L + I, and I, the rates of synthesis of butyrate (mean ± SEM) were 10.6 ± 3.2, 23.3 ± 4.5, 12.4 ± 3.6, and 14.6 ± 4.0 µmol/min, respectively (Group Effect, P = 0.1; C vs. L, P = 0.03; L vs. L + I, P = 0.06). The cecal butyrate concentrations did not differ among the 4 groups and were 8.7 ± 3.2, 2.4 ± 0.8, 3.4 ± 1.9, and 2.0 ± 0.7 µmol/g dry wt, respectively. The total cecal cell proliferation index was higher in C than in L (P = 0.008) or I (P = 0.026) and was higher in L + I than in L (P = 0.013) or I (P = 0.046). The increased supply of butyrate to the cecum was associated with decreased cell proliferation, but cecal butyrate concentration did not reflect synthesis.

KEY WORDS: • butyrate • lactulose • inulin • swine • colon

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