The Effect of Feeding Liquid or Dry Creep Feed on Growth Performance, Feed Disappearance, Enzyme Activity and Number of Eaters in Suckling Piglets.

The aim of this study was to investigate the effect of two dietary treatments (liquid creep feed (LCF) and dry creep feed (DCF)) offered during the suckling period on feed disappearance, number of eaters, and intestinal enzymatic development at weaning in an on-farm study with 347 piglets. Piglets were allocated to either the DCF or LCF treatment from day 10 to day 24 postpartum for 9 h a day. Red ferric oxide (1%) was added to the diet to categorize piglets into eating categories (good eaters, moderate eaters, or non-eaters) via faecal swabs. At weaning, 40 piglets were sampled for intestinal enzymatic development. The LCF treatment increased the dry matter disappearance from day 10-18 (p < 0.001). The percentage of good eaters, moderate eaters and non-eaters did not differ between treatments (p > 0.05). The DCF pigs displayed greater average daily gain (ADG) pre-weaning (p = 0.024), and a greater body weight (BW) at day 61 (p < 0.001). The activity of lactase, maltase and sucrase in the proximal part of the small intestine were greatest (p < 0.001) in the DCF pigs.

Sex-Specific Survival, Growth, Immunity and Organ Development in Preterm Pigs as Models for Immature Newborns.

Background: After very preterm birth, male infants show higher mortality than females, with higher incidence of lung immaturity, neurological deficits, infections, and growth failure. In modern pig production, piglets dying in the perinatal period (up to 20%) often show signs of immature organs, but sex-specific effects are not clear. Using preterm pigs as model for immature infants and piglets, we hypothesized that neonatal survival and initial growth and immune development depend on sex. Methods: Using data from a series of previous intervention trials with similar delivery and rearing procedures, we established three cohorts of preterm pigs (90% gestation), reared for 5, 9, or 19 days before sample collection (total n = 1,938 piglets from 109 litters). Partly overlapping endpoints among experiments allowed for multiple comparisons between males and females for data on mortality, body and organ growth, gut, immunity, and brain function. Results: Within the first 2 days, males showed higher mortality than females (18 vs. 8%, P < 0.001), but less severe immune response to gram-positive infection. No effect of sex was observed for thermoregulation or plasma cortisol. Later, infection resistance did not differ between sexes, but growth rate was reduced for body (up to -40%) and kidneys (-6%) in males, with higher leucocyte counts (+15%) and lower CD4 T cell fraction (-5%) on day 9 and lower monocyte counts (-18%, day 19, all P < 0.05). Gut structure, function and necrotizing enterocolitis (NEC) incidence were similar between groups, but intestinal weight (-3%) and brush-border enzyme activities were reduced at day 5 (lactase, DPP IV, -8%) in males. Remaining values for blood biochemistry, hematology, bone density, regional brain weights, and visual memory (tested in a T maze) were similar. Conclusion: Following preterm birth, male pigs show higher mortality and slower growth than females, despite limited differences in organ growth, gut, immune, and brain functions. Neonatal intensive care procedures may be particularly important for compromised newborns of the male sex. Preterm pigs can serve as good models to study the interactions of sex- and maturation-specific survival and physiological adaptation in mammals.

Specific gut microbiome members are associated with distinct immune markers in pediatric allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Increasing evidence reveals the importance of the microbiome in health and disease and inseparable host-microbial dependencies. Host-microbe interactions are highly relevant in patients receiving allogeneic hematopoietic stem cell transplantation (HSCT), i.e., a replacement of the cellular components of the patients' immune system with that of a foreign donor. HSCT is employed as curative immunotherapy for a number of non-malignant and malignant hematologic conditions, including cancers such as acute lymphoblastic leukemia. The procedure can be accompanied by severe side effects such as infections, acute graft-versus-host disease (aGvHD), and death. Here, we performed a longitudinal analysis of immunological markers, immune reconstitution and gut microbiota composition in relation to clinical outcomes in children undergoing HSCT. Such an analysis could reveal biomarkers, e.g., at the time point prior to HSCT, that in the future could be used to predict which patients are of high risk in relation to side effects and clinical outcomes and guide treatment strategies accordingly. RESULTS: In two multivariate analyses (sparse partial least squares regression and canonical correspondence analysis), we identified three consistent clusters: (1) high concentrations of the antimicrobial peptide human beta-defensin 2 (hBD2) prior to the transplantation in patients with high abundances of Lactobacillaceae, who later developed moderate or severe aGvHD and exhibited high mortality. (2) Rapid reconstitution of NK and B cells in patients with high abundances of obligate anaerobes such as Ruminococcaceae, who developed no or mild aGvHD and exhibited low mortality. (3) High inflammation, indicated by high levels of C-reactive protein, in patients with high abundances of facultative anaerobic bacteria such as Enterobacteriaceae. Furthermore, we observed that antibiotic treatment influenced the bacterial community state. CONCLUSIONS: We identify multivariate associations between specific microbial taxa, host immune markers, immune cell reconstitution, and clinical outcomes in relation to HSCT. Our findings encourage further investigations into establishing longitudinal surveillance of the intestinal microbiome and relevant immune markers, such as hBD2, in HSCT patients. Profiling of the microbiome may prove useful as a prognostic tool that could help identify patients at risk of poor immune reconstitution and adverse outcomes, such as aGvHD and death, upon HSCT, providing actionable information in guiding precision medicine.

Antibiotics increase gut metabolism and antioxidant proteins and decrease acute phase response and necrotizing enterocolitis in preterm neonates.

BACKGROUND: The appropriate use of antibiotics for preterm infants, which are highly susceptible to develop necrotizing enterocolitis (NEC), is not clear. While antibiotic therapy is commonly used in neonates with NEC symptoms and sepsis, it remains unknown how antibiotics may affect the intestine and NEC sensitivity. We hypothesized that broad-spectrum antibiotics, given immediately after preterm birth, would reduce NEC sensitivity and support intestinal protective mechanisms. METHODOLOGY/PRINCIPAL FINDINGS: Preterm pigs were treated with antibiotics for 5 d (oral and systemic doses of gentamycin, ampicillin and metrodinazole; AB group) and compared with untreated pigs. Only the untreated pigs showed evidence of NEC lesions and reduced digestive function, as indicated by lowered villus height and activity of brush border enzymes. In addition, 53 intestinal and 22 plasma proteins differed in expression between AB and untreated pigs. AB treatment increased the abundance of intestinal proteins related to carbohydrate and protein metabolism, actin filaments, iron homeostasis and antioxidants. Further, heat shock proteins and the complement system were affected suggesting that all these proteins were involved in the colonization-dependent early onset of NEC. In plasma, acute phase proteins (haptoglobin, complement proteins) decreased, while albumin, cleaved C3, ficolin and transferrin increased. CONCLUSIONS/SIGNIFICANCE: Depressed bacterial colonization following AB treatment increases mucosal integrity and reduces bacteria-associated inflammatory responses in preterm neonates. The plasma proteins C3, ficolin, and transferrin are potential biomarkers of the colonization-dependent NEC progression in preterm neonates.

Diet-dependent effects of minimal enteral nutrition on intestinal function and necrotizing enterocolitis in preterm pigs.

BACKGROUND: A rapid advance in enteral feeding is associated with necrotizing enterocolitis (NEC) in preterm infants. Therefore, minimal enteral nutrition (MEN) combined with parenteral nutrition (PN) is common clinical practice, but the effects on NEC and intestinal function remain poorly characterized. It was hypothesized that a commonly used MEN feeding volume (16-24 mL/kg/d) prevents NEC and improves intestinal structure, function, and microbiology in preterm pigs. METHODS: After preterm birth pigs were stratified into 4 nutrition intervention groups that received the following treatments: (1) PN followed by full enteral formula feeding (OF group, n = 12); (2) PN supplemented with formula MEN and followed by full formula feeding (FF, n = 12); (3) PN plus colostrum MEN followed by formula feeding (CF, n = 12); (4) PN plus colostrum MEN followed by colostrum feeding (CC, n = 10). RESULTS: NEC was absent in the CC group but frequent in the other groups (50%-67%). Compared with other groups, CC pigs showed improved mucosal structures, brush border enzyme activities, and hexose absorption (all P < .05). Relative to formula MEN, colostrum MEN thus improved gut function but did not prevent later formula-induced gut dysfunction and NEC. However, in CF pigs, intestinal lesions were restricted to the colon, compared with all regions in OF and FF pigs, which indicated proximal protection of colostrum MEN. Bacterial composition was not affected by MEN, diet, or NEC outcomes, but bacterial load and concentrations of short-chain fatty acids were reduced in the MEN groups. CONCLUSION: Colostrum MEN improves intestinal structure, function, and NEC resistance in preterm pigs but does not protect against gut dysfunction and NEC associated with later full enteral formula feeding.