Spray Dried, Pasteurised Bovine Colostrum Protects Against Gut Dysfunction and Inflammation in Preterm Pigs

Abstract

which also donated the colostrum for the study. Biofiber-Damino had no role in the design, analysis or writing of this article. University of Copenhagen has filed a patent application regarding the use of bovine colostrum for paediatric patients. Per Sangild is listed as sole inventor but has declined Copyright © ESPGHAN and NASPGHAN. All rights reserved. AbstractObjective: Feeding bovine colostrum (BC) improves gut maturation and function, and protects against necrotizing enterocolitis (NEC), relative to formula in newborn preterm pigs. Before BC can be used for preterm infants, it is important to test if the milk processing, required to reduce bacterial load and increase shelf life, may affect bioactivity and efficacy of a BC product. Methods:We investigated if spray dried, and pasteurised, spray dried BC had protective effects on gut function in preterm pigs, relative to formula. After a 2-day total parenteral nutrition period, preterm pigs were fed formula for a few hours (to induce a pro-inflammatory state) followed by 2 days of formula (FORM, n = 14), BC (COLOS, n = 14), spray dried BC (POW, n = 8), or pasteurised, spray dried BC (POWPAS, n = 9).Results: Spray drying and pasteurisation of BC decreased the concentration of TGF-β1, TGF-β2 and increased protein aggregation. All three BC groups had reduced NEC severity, small intestinal levels of IL-1β, IL-8 and colonic lactic acid levels, and increased intestinal villus height, hexose Copyright © ESPGHAN and NASPGHAN. All rights reserved.3 absorption, and digestive enzyme activities, relative to the FORM group (all P < 0.05). All three BC diets stimulated epithelial cell migration in a wound-healing model with IEC-6 cells. Conclusion:Spray drying and pasteurisation affect BC proteins, but do not reduce the trophic and anti-inflammatory effects on the immature intestine. It remains to be studied if BC products will benefit preterm infants just after birth when human milk is often not available. Keywords: animal model, necrotizing enterocolitis, formula, diet, prematurity What is known• Mother's milk and bovine colostrum have a high level of bioactive factors while formula lacks such factors.• Bovine colostrum improves gut maturation, function and necrotizing enterocolitis resistance, relative to formula in preterm pigs.• Processing of milk products is required for use in clinical settings, but this may also reduce their bioactivity. What is new• Pasteurised, spray dried bovine colostrum reduces necrotizing enterocolitis and inflammation and increases gut function, relative to infant formula in preterm pigs.• Spray drying does not markedly damage colostrum milk proteins, while pasteurisation results in some protein aggregation and reduced concentration of bioactive factors.

Increased Intestinal Inflammation and Digestive Dysfunction in Preterm Pigs with Severe Necrotizing Enterocolitis

“…Mild NEC did not clearly affect these genes, although multiple tissue sampling times over a longer feeding period might have indicated gradually increasing gene expressions. We have previously observed moderate positive correlations between NEC severity and IL1B or CXCL8 expression but a limited effect on IL6 [10,12,13]. Prevention of NEC with oral antibiotics downregulates CXCL8 and TLR2 (7- to 10-fold) [20], but TLR2 failed to be differentially regulated in this study.…”

“…The most severe NEC cases developed within a range of 12-45 h after enteral food introduction, which could indicate different disease progressions and time frames of the intermediate NEC stages. Increased bacterial density correlates with increasing NEC severity in preterm pigs [12,13], and this may play a role in early NEC events [4,19]. At a certain threshold of bacterial load, inflammatory reactions may set off mucosal dysfunctions, leading to more severe NEC.…”

“…Forty-eight preterm pigs were delivered by cesarean section (105-107 days of gestation, term 116 days) and surgical procedures, rearing, euthanasia, and clinical evaluation were performed as previously described [6,12,13]. After a 2-day total parenteral nutrition period, the pigs were fed enteral diets [for further details, see [12,13]] consisting of bovine colostrum (BC, n = 6), milk formula ( n = 13), or milk formula for 6 h followed by BC products (BC, spray-dried BC, or pasteurized + spray-dried BC, n = 29).…”

“…After a 2-day total parenteral nutrition period, the pigs were fed enteral diets [for further details, see [12,13]] consisting of bovine colostrum (BC, n = 6), milk formula ( n = 13), or milk formula for 6 h followed by BC products (BC, spray-dried BC, or pasteurized + spray-dried BC, n = 29). The pigs were euthanized if symptoms of NEC (including abdominal distension, lethargy, cyanosis, and/or bloody diarrhea) were observed, or at the end of study period (45-52 h after enteral food introduction).…”

“…We hypothesized that only severe macroscopic NEC lesions would be associated with intestinal inflammation and dysfunction, suggesting that disturbed digestion and immune responses are more a consequence than a cause of NEC. Therefore, tissues from some previous NEC studies using diet interventions [12,13,14] were reinvestigated with regard to NEC severity, inflammatory gene expression, villous morphology, and digestive function specifically for the distal intestine, where NEC lesions are most common when detected in the small intestine.…”