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.

Glucagon-like peptide-2 and short-chain fatty acids: a new twist to an old story.

The nutritional regulation of intestinal adaptation extends beyond the route of nutrient administration as specific nutrients are known to mediate the adaptive response. Dietary carbohydrates are known to enhance intestinal adaptation in patients with short-bowel syndrome. This review discusses SCFA-induced adaptation in intestinal structure and function in adult rat and neonatal piglet models. Potential mechanisms relate to the salvage of energy as SCFA in the colon, direct mediation of intestinal adaptation by SCFA and stimulated release of glucagon-like peptide-2 (GLP-2) from enteroendocrine L cells by SCFA. Among the produced SCFA, butyrate appears to be responsible for increasing plasma GLP-2 concentration, in addition to the enterotrophic effects. Emerging evidence reveals that physiological concentrations of butyrate acutely upregulate the expression of key enterocyte-associated nutrient transporters. Focused experiments are needed to carefully identify the critical components of intestinal adaptation and yield conclusions regarding the relative contributions of SCFA and GLP-2 during the various phases of this process.