Effects of the in vivo supply of butyrate on histone acetylation of cecum in piglets.
BACKGROUND
In vitro, butyrate inhibits histone deacetylase and down-regulates expression of cyclin D1. We hypothesized that an increased entry rate of butyrate into the cecal lumen would have similar effects in vivo.


METHODS
We used frozen cecal tissue and data from previous studies, one showing that lactulose supplementation caused an increased rate of cecal synthesis of butyrate and decreased cecal cell proliferation and density of clostridia and the other showing that cecal cell proliferation was increased by an exogenous cecal butyrate infusion at a comparable rate. The ratio of acetylated to total histones (AH ratio) and cyclin D1 mRNA expression were measured in cecal tissue.


RESULTS
Lactulose supplementation caused a 189% increase in the AH ratio (p = .004), which inversely correlated with cecal cell proliferation (r = -0.782; p = .008). With cecal butyrate infusion, we observed a significant decrease in histone acetylation (p = .02), which also inversely correlated with cecal cell proliferation (r = -0.797; p = .002). Cyclin D1 expression was increased 6.5-fold by lactulose feeding (p = .02) but decreased 50% with cecal butyrate infusion (p = .004).


CONCLUSIONS
The effects on histone acetylation of increased "endogenous" butyrate production produced by lactulose feeding, but not exogenous cecal infusion of butyrate, mirror those in vitro. Thus, bacterial production and exogenous infusion of butyrate have opposite effects on histone acetylation and cyclin D1 expression, suggesting that the composition of bacterial flora may play a role in butyrate's in vivo effects on the cell cycle.
Kien
C Lawrence
CL
Department of Pediatrics, College of Medicine, University of Vermont, Burlington, Vermont 05405, USA. cl.kien@uvm.edu
Peltier
Cheryl P
CP
Mandal
Soma
S
Davie
James R
JR
Blauwiekel
Ruth
R
D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D002087:Butyrates / Q000494:pharmacology*; D002432:Cecum / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism*; D004195:Disease Models, Animal; D005765:Gastrointestinal Agents / Q000494:pharmacology; D005786:Gene Expression Regulation; D056572:Histone Deacetylase Inhibitors; D006657:Histones / Q000187:drug effects / Q000378:metabolism*; D007792:Lactulose / Q000494:pharmacology; D013552:Swine
D002087:Butyrates; D005765:Gastrointestinal Agents; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D019938:Cyclin D1; D007792:Lactulose