Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets.
BACKGROUND
Supplementation of total parenteral nutrition (TPN) with a mixture of short-chain fatty acids (SCFA) enhances intestinal adaptation in the adult rodent model. However, the ability and timing of SCFA to augment adaptation in the neonatal intestine is unknown. Furthermore, the specific SCFA inducing the intestinotrophic effects and underlying regulatory mechanism(s) are unclear. Therefore, we examined the effect of SCFA supplemented TPN on structural aspects of intestinal adaptation and hypothesized that butyrate is the SCFA responsible for these effects.


METHODS
Piglets (n = 120) were randomized to (1) control TPN or TPN supplemented with (2) 60 mmol/L SCFA (36 mmol/L acetate, 15 mmol/L propionate and 9 mmol/L butyrate), (3) 9 mmol/L butyrate, or (4) 60 mmol/L butyrate. Within each group, piglets were further randomized to examine acute (4, 12, or 24 hours) and chronic (3 or 7 days) adaptations. Indices of intestinal adaptation, including crypt-villus architecture, proliferation and apoptosis, and concentration of the intestinotrophic peptide, glucagon-like pepide-2 (GLP-2), were measured.


RESULTS
Villus height was increased (p < .029) within 4 hours by supplemented TPN treatments. Supplemented TPN treatments increased (p < .037) proliferating cell nuclear antigen expression along the entire intestine. Indicative of an antiapoptotic profile, jejunal Bax:Bcl-w abundance was decreased (p = .033) by both butyrate-supplemented TPN treatments, and ileal abundance was decreased (p = .0002) by all supplemented TPN treatments, regardless of time. Supplemented TPN treatments increased (p = .016) plasma GLP-2 concentration at all time points.


CONCLUSIONS
Butyrate is the SCFA responsible for augmenting structural aspects of intestinal adaptations by increasing proliferation and decreasing apoptosis within 4 hours postresection. The intestinotrophic mechanism(s) underlying butyrate's effects may involve GLP-2. Ultimately, butyrate administration may enable an infant with short-bowel syndrome to successfully transition to enteral feedings by maximizing their absorptive area.
Division of Nutritional Sciences, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Anne L
AL
Bartholome
David M
DM
Albin
David H
DH
Baker
Jens J
JJ
Holst
Kelly A
KA
Tappenden
D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000008:administration & dosage / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005232:Fatty Acids, Volatile / Q000008:administration & dosage / Q000494:pharmacology; D053767:Glucagon-Like Peptide 2; D004763:Glucagon-Like Peptides; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000473:pathology / Q000502:physiology / Q000601:surgery; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines / Q000187:drug effects / Q000502:physiology* / Q000601:surgery; D007583:Jejunum / Q000378:metabolism / Q000473:pathology / Q000502:physiology / Q000601:surgery; D010289:Parenteral Nutrition, Total; D010455:Peptides / Q000097:blood / Q000378:metabolism*; D011897:Random Allocation; D012778:Short Bowel Syndrome / Q000628:therapy*; D013552:Swine
D002087:Butyrates; D005232:Fatty Acids, Volatile; D053767:Glucagon-Like Peptide 2; D010455:Peptides; D004763:Glucagon-Like Peptides