Intestinal epithelial proliferation and villus height increased by short-chain fatty acid supplemented total parenteral nutrition following 80% jejunoileal resection in piglets
Bartholome, A.L.; Albin, D.M.; Tappenden, K.A.
FASEB Journal 17(4-5): Abstract 771
Necrotizing enterocolitis is the most common surgical emergency among premature infants, often leaving inadequate surface area for digestion and absorption. Therefore, the hypothesis that short-chain fatty acid supplemented total parenteral nutrition (TPN) enhances intestinal structure following 80% jejunoileal resection was tested. Piglets (1.6+-0.1 kg, n=120) were randomized to: 1) control TPN, or TPN supplemented with; 2) 60 mM SCFAs (36 mM acetate, 15 mM propionate and 9 mM butyrate; SCFA); 3) 9 mM butyrate (9Bu), or; 4) 60 mM butyrate (60Bu).)Within each group, animals were further randomized to examine acute (4h, 12h, 24h) and chronic (d3 or d7) adaptations. Morphometry revealed increased jejunal and ileal villus height (p<0.0001) and surface area (p<0.0001) in the SCFA, 9Bu and 60Bu groups compared to the control group, regardless of time. Protein abundance of proliferating cell nuclear antigen was lowest (p=0.017) in the control group, whereas active caspase-3 subunits were not altered by diet. Effect of diet on proliferation was greatest (p=0.025) at 4h with villus height peaking (p<0.0001) at d3. These results indicate that short-chain fatty acids or butyrate alone enhance epithelial proliferation (rather than altering apoptosis) to increase intestinal surface area and may reduce TPN dependence of children with short-bowel syndrome.