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The postprandial plasma essential amino acid (AA) peak concentrations of infant formula (IF) are higher than those of human milk (HM) in infants. In addition, several HM proteins have been recovered intact in infant stool and appeared digestion resistant in vitro. We, therefore, hypothesized that gastrointestinal protein hydrolysis of IF is faster than HM and leads to accelerated absorbable digestion product release. HM and IF protein hydrolysis kinetics were compared in a two-step semi-dynamic in vitro infant digestion model, and the time course of degree of protein hydrolysis (DH), loss of intact protein, and release of free AA and peptides was evaluated. Gastric DH increase was similar for IF and HM, but the rate of intestinal DH increase was 1.6 times higher for IF than HM. Intact protein loss in IF was higher than HM from 120 min gastric phase until 60 min intestinal phase. Intestinal phase total digestion product (free AA + peptides <5 kDa) concentrations increased ~2.5 times faster in IF than HM. IF gastrointestinal protein hydrolysis and absorbable product release are faster than HM, possibly due to the presence of digestion-resistant proteins in HM. This might present an opportunity to further improve IF bringing it closer to HM.

The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development.

Background: The compromised gut microbiome that results from C-section birth has been hypothesized as a risk factor for the development of non-communicable diseases (NCD). In a double-blind randomized controlled study, 153 infants born by elective C-section received an infant formula supplemented with either synbiotic, prebiotics, or unsupplemented from birth until 4 months old. Vaginally born infants were included as a reference group. Stool samples were collected from day 3 till week 22. Multi-omics were deployed to investigate the impact of mode of delivery and nutrition on the development of the infant gut microbiome, and uncover putative biological mechanisms underlying the role of a compromised microbiome as a risk factor for NCD. Results: As early as day 3, infants born vaginally presented a hypoxic and acidic gut environment characterized by an enrichment of strict anaerobes (Bifidobacteriaceae). Infants born by C-section presented the hallmark of a compromised microbiome driven by an enrichment of Enterobacteriaceae. This was associated with meta-omics signatures characteristic of a microbiome adapted to a more oxygen-rich gut environment, enriched with genes associated with reactive oxygen species metabolism and lipopolysaccharide biosynthesis, and depleted in genes involved in the metabolism of milk carbohydrates. The synbiotic formula modulated expression of microbial genes involved in (oligo)saccharide metabolism, which emulates the eco-physiological gut environment observed in vaginally born infants. The resulting hypoxic and acidic milieu prevented the establishment of a compromised microbiome. Conclusions: This study deciphers the putative functional hallmarks of a compromised microbiome acquired during C-section birth, and the impact of nutrition that may counteract disturbed microbiome development. Trial registration: The study was registered in the Dutch Trial Register (Number: 2838) on 4th April 2011.

Functionality of the gastrointestinal tract is essential for growth and development of newborns. Preterm infants have an immature gastrointestinal tract, which is a major challenge in neonatal care. This study aims to improve the understanding of gastrointestinal functionality and maturation during the early life of preterm infants by means of gastrointestinal enzyme activity assays and metaproteomics. In this single-center, observational study, preterm infants born between 24 and 33 weeks (n = 40) and term infants born between 37 and 42 weeks (n = 3), who were admitted to Isala (Zwolle, the Netherlands), were studied. Enzyme activity analyses identified active proteases in gastric aspirates of preterm infants. Metaproteomics revealed human milk, digestive and immunological proteins in gastric aspirates of preterm infants and feces of preterm and term infants. The fecal proteome of preterm infants was deprived of gastrointestinal barrier-related proteins during the first six postnatal weeks compared to term infants. In preterm infants, bacterial oxidative stress proteins were increased compared to term infants and higher birth weight correlated to higher relative abundance of bifidobacterial proteins in postnatal week 3 to 6. Our findings indicate that gastrointestinal and beneficial microbial proteins involved in gastrointestinal maturity are associated with gestational and postnatal age.

Human milk is the optimal diet for infant development, but infant milk formula (IMF) must be available as an alternative. To develop high-quality IMF, bovine milk processing is required to ensure microbial safety and to obtain a protein composition that mimics human milk. However, processing can impact the quality of milk proteins, which can influence gastro-intestinal (GI) tolerance by changing digestion, transit time and/or absorption. The aim of this study was to evaluate the impact of structural changes of proteins due to thermal processing on gastro-intestinal tolerance in the immature GI tract. Preterm and near-term piglets received enteral nutrition based on whey protein concentrate (WPC) either mildly pasteurized (MP-WPC) or extensively heated (EH-WPC). Clinical symptoms, transit time and gastric residuals were evaluated. In addition, protein coagulation and protein composition of coagulates formed during in vitro digestion were analyzed in more detail. Characterization of MP-WPC and EH-WPC revealed that mild pasteurization maintained protein nativity and reduced aggregation of β-lactoglobulin and α-lactalbumin, relative to EH-WPC. Mild pasteurization reduced the formation of coagulates during digestion, resulting in reduced gastric residual volume and increased intestinal tract content. In addition, preterm piglets receiving MP-WPC showed reduced mucosal bacterial adherence in the proximal small intestine. Finally, in vitro digestion studies revealed less protein coagulation and lower levels of β-lactoglobulin and α-lactalbumin in the coagulates of MP-WPC compared with EH-WPC. In conclusion, minimal heat treatment of WPC compared with extensive heating promoted GI tolerance in immature piglets, implying that minimal heated WPC could improve the GI tolerance of milk formulas in infants.

Background. The human digestive tract is structurally mature at birth, yet maturation of gut functions such as digestion and mucosal barrier continues for the next 1–2 years. Human milk and infant milk formulas (IMF) seem to impact maturation of these gut functions differently, which is at least partially related to high temperature processing of IMF causing loss of bioactive proteins and formation of advanced glycation end products (AGEs). Both loss of protein bioactivity and formation of AGEs depend on heating temperature and time. The aim of this study was to investigate the impact of mildly pasteurized whey protein concentrate (MP-WPC) compared to extensively heated WPC (EH-WPC) on gut maturation in a piglet model hypersensitive to enteral nutrition. Methods. WPC was obtained by cold filtration and mildly pasteurized (73 °C, 30 s) or extensively heat treated (73 °C, 30 s + 80 °C, 6 min). Preterm (~90% gestation) and near-term piglets (~96% gestation) received enteral nutrition based on MP-WPC or EH-WPC for five days. Macroscopic and histologic lesions in the gastro-intestinal tract were evaluated and intestinal responses were further assessed by RT-qPCR, immunohistochemistry and enzyme activity analysis. Results. A diet based on MP-WPC limited epithelial intestinal damage and improved colonic integrity compared to EH-WPC. MP-WPC dampened colonic IL1-β, IL-8 and TNF-α expression and lowered T-cell influx in both preterm and near-term piglets. Anti-microbial defense as measured by neutrophil influx in the colon was only observed in near-term piglets, correlated with histological damage and was reduced by MP-WPC. Moreover, MP-WPC stimulated iALP activity in the colonic epithelium and increased differentiation into enteroendocrine cells compared to EH-WPC. Conclusions. Compared to extensively heated WPC, a formula based on mildly pasteurized WPC limits gut inflammation and stimulates gut maturation in preterm and near-term piglets and might therefore also be bene

Human milk is the optimal diet for infant development, but infant milk formula (IMF) must be available as an alternative. To develop high-quality IMF, bovine milk processing is required to ensure microbial safety and to obtain a protein composition that mimics human milk. However, processing can impact the quality of milk proteins, which can influence gastro-intestinal (GI) tolerance by changing digestion, transit time and/or absorption. The aim of this study was to evaluate the impact of structural changes of proteins due to thermal processing on gastro-intestinal tolerance in the immature GI tract. Preterm and near-term piglets received enteral nutrition based on whey protein concentrate (WPC) either mildly pasteurized (MP-WPC) or extensively heated (EH-WPC). Clinical symptoms, transit time and gastric residuals were evaluated. In addition, protein coagulation and protein composition of coagulates formed during in vitro digestion were analyzed in more detail. Characterization of MP-WPC and EH-WPC revealed that mild pasteurization maintained protein nativity and reduced aggregation of β-lactoglobulin and α-lactalbumin, relative to EH-WPC. Mild pasteurization reduced the formation of coagulates during digestion, resulting in reduced gastric residual volume and increased intestinal tract content. In addition, preterm piglets receiving MP-WPC showed reduced mucosal bacterial adherence in the proximal small intestine. Finally, in vitro digestion studies revealed less protein coagulation and lower levels of β-lactoglobulin and α-lactalbumin in the coagulates of MP-WPC compared with EH-WPC. In conclusion, minimal heat treatment of WPC compared with extensive heating promoted GI tolerance in immature piglets, implying that minimal heated WPC could improve the GI tolerance of milk formulas in infants.

Background. The human digestive tract is structurally mature at birth, yet maturation of gut functions such as digestion and mucosal barrier continues for the next 1–2 years. Human milk and infant milk formulas (IMF) seem to impact maturation of these gut functions differently, which is at least partially related to high temperature processing of IMF causing loss of bioactive proteins and formation of advanced glycation end products (AGEs). Both loss of protein bioactivity and formation of AGEs depend on heating temperature and time. The aim of this study was to investigate the impact of mildly pasteurized whey protein concentrate (MP-WPC) compared to extensively heated WPC (EH-WPC) on gut maturation in a piglet model hypersensitive to enteral nutrition. Methods. WPC was obtained by cold filtration and mildly pasteurized (73 °C, 30 s) or extensively heat treated (73 °C, 30 s + 80 °C, 6 min). Preterm (~90% gestation) and near-term piglets (~96% gestation) received enteral nutrition based on MP-WPC or EH-WPC for five days. Macroscopic and histologic lesions in the gastro-intestinal tract were evaluated and intestinal responses were further assessed by RT-qPCR, immunohistochemistry and enzyme activity analysis. Results. A diet based on MP-WPC limited epithelial intestinal damage and improved colonic integrity compared to EH-WPC. MP-WPC dampened colonic IL1-β, IL-8 and TNF-α expression and lowered T-cell influx in both preterm and near-term piglets. Anti-microbial defense as measured by neutrophil influx in the colon was only observed in near-term piglets, correlated with histological damage and was reduced by MP-WPC. Moreover, MP-WPC stimulated iALP activity in the colonic epithelium and increased differentiation into enteroendocrine cells compared to EH-WPC. Conclusions. Compared to extensively heated WPC, a formula based on mildly pasteurized WPC limits gut inflammation and stimulates gut maturation in preterm and near-term piglets and might therefore also be bene

Birth by Caesarean (C)-section impacts early gut microbiota colonization and is associated with an increased risk of developing immune and metabolic disorders. Moreover, alterations of the microbiome have been shown to affect neurodevelopmental trajectories. However, the long-term effects of C-section on neurobehavioral processes remain unknown. Here, we demonstrated that birth by C-section results in marked but transient changes in microbiome composition in the mouse, in particular, the abundance of Bifidobacterium spp. was depleted in early life. Mice born by C-section had enduring social, cognitive, and anxiety deficits in early life and adulthood. Interestingly, we found that these specific behavioral alterations induced by the mode of birth were also partially corrected by co-housing with vaginally born mice. Finally, we showed that supplementation from birth with a Bifidobacterium breve strain, or with a dietary prebiotic mixture that stimulates the growth of bifidobacteria, reverses selective behavioral alterations in C-section mice. Taken together, our data link the gut microbiota to behavioral alterations in C-section-born mice and suggest the possibility of developing adjunctive microbiota-targeted therapies that may help to avert long-term negative consequences on behavior associated with C-section birth mode.

BACKGROUND: It is important to understand the consequences of pre-emptive antibiotic treatment in neonates, as disturbances in microbiota development during this key developmental time window might affect early and later life health outcomes. Despite increasing knowledge regarding the detrimental effect of antibiotics on the gut microbiota, limited research focussed on antibiotic treatment duration. We determined the effect of short and long amoxicillin/ceftazidime administration on gut microbiota development during the immediate postnatal life of preterm and term infants. METHODS: Faeces was collected from 63 (pre) term infants at postnatal weeks one, two, three, four and six. Infants received either no (control), short-term (ST) or long-term (LT) postpartum amoxicillin/ceftazidime treatment. RESULTS: Compared to control infants, ST and LT infants' microbiota contained significantly higher abundance of Enterococcus during the first two postnatal weeks at the expense of Bifidobacterium and Streptococcus. Short and long antibiotic treatment both allowed for microbiota restoration within the first six postnatal weeks. However, Enterococcus and Bifidobacterium abundances were affected in fewer ST than LT infants. CONCLUSIONS: Intravenous amoxicillin/ceftazidime administration affects intestinal microbiota composition by decreasing the relative abundance of Escherichia-Shigella and Streptococcus, while increasing the relative abundance of Enterococcus and Lactobacillus species during the first two postnatal weeks. Thriving of enterococci at the expense of bifidobacteria and streptococci should be considered as aspect of the cost-benefit determination for antibiotic prescription.

Background Preterm infants are born with an immature gut, brain, and immune system, predisposing them to short- and long-term complications. Objective We hypothesized that a milk diet supplemented with pre- and probiotics (i.e. synbiotics) and glutamine would improve gut, brain, and immune maturation in preterm neonates, using preterm pigs as a model. Methods Preterm pigs (Landrace x Yorkshire x Duroc, n = 40, delivered by c-section at 90% of gestation) were reared individually until day 23 after birth under highly standardized conditions. Piglets in the intervention group (PPG, n = 20) were fed increasing volumes of bovine milk supplemented with prebiotics (short-chain galacto- and long chain fructo-oligosaccharides 9:1, 4-12 g/L), probiotics (Bifidobacterium breve M16-V, 3 × 10 9 CFU/d) and l-glutamine [0.15-0.30 g/(kg · d)], and compared with pigs fed bovine milk with added placebo compounds as control (CON, n = 20). Clinical, gastrointestinal, immunological, cognitive, and neurological endpoints were measured. Results The PPG pigs showed more diarrhea but weight gain, body composition, and gut parameters were similar between the groups. Cognitive performance, assessed in a T-maze, was significantly higher in PPG pigs (P < 0.01), whereas motor function and exploratory interest were similar between the groups. Using ex vivo diffusion imaging, the orientation dispersion index in brain cortical gray matter was 50% higher (P = 0.04), and fractional anisotropy value was 7% lower (P = 0.05) in PPG pigs compared with CON pigs, consistent with increased dendritic branching in PPG. In associative fibers, radial diffusivity was lower and fractional anisotropy was higher in PPG pigs compared with CON pigs (all P < 0.05), while measures in the internal capsule showed a tendency towards reduced radial diffusivity and mean diffusivity (both P = 0.09). On day 23 pigs in the PPG group showed higher blood leukocyte numbers (+43%), neutrophil counts (+100%), and phagocyti

Background: Multiple studies have indicated that formula-fed infants show a different growth trajectory compared with breastfed infants. The observed growth rates are suggested to be linked to higher postprandial levels of branched chain amino acids (BCAAs) and insulin related to differences in protein quality. Objective: We evaluated the effects of milk protein denaturation and milk protein composition on postprandial plasma and hormone concentrations. Methods: Neonatal piglets were bolus-fed randomly, in an incomplete crossover design, 2 of 3 milk protein solutions: Native whey protein isolate (NWPI), denatured whey protein isolate (DWPI), or protein base ingredient, comprising whey and casein (PBI). Postprandial plasma amino acids (AAs), insulin, glucagon-like peptide 1, glucose, and paracetamol concentrations were assayed. Plasma responses were fitted with a model of first-order absorption with linear elimination. Results: DWPI (91% denatured protein) compared with NWPI (91% native protein) showed lower essential amino acids (EAAs) (∼10%) and BCAA (13-19%) concentrations in the first 30-60 min. However, total amino acid (TAA) concentration per time-point and area under the curve (AUC), as well as EAA and BCAA AUC were not different. PBI induced a ∼30% lower postprandial insulin spike than NWPI, yet plasma TAA concentration at several time-points and AUC was higher in PBI than in NWPI. The TAA rate constant for absorption (ka) was twofold higher in PBI than in NWPI. Plasma BCAA levels from 60 to 180 min and AUC were higher in PBI than in NWPI. Plasma EAA concentrations and AUCs in PBI and NWPI were not different. Conclusions: Denaturation of WPI had a minimal effect on postprandial plasma AA concentration. The differences between PBI and NWPI were partly explained by the difference in AA composition, but more likely differences in protein digestion and absorption kinetics. We conclude that modifying protein composition, but not denaturation, of milk protein solut

Microbiota development in (pre)term infants receiving various durations of postpartum antibiotic treatment. Determined through 16S rRNA gene amplicon sequencing (MiSeq, Illumina)., Background It is important to understand the consequences of pre-emptive antibiotic treatment in neonates, as disturbances in microbiota development during this key developmental time window might affect early and later life health outcomes. Despite increasing knowledge regarding the detrimental effect of antibiotics on the gut microbiota, limited research focussed on antibiotic treatment duration. We determined the effect of short and long amoxicillin/ceftazidime administration on gut microbiota development during the immediate postnatal life of preterm and term infants. Methods Faeces was collected from 63 (pre) term infants at postnatal weeks one, two, three, four and six. Infants received either no (control), short-term (ST) or long-term (LT) postpartum amoxicillin/ceftazidime treatment. Results Compared to control infants, ST and LT infants’ microbiota contained significantly higher abundance of Enterococcus during the first two postnatal weeks at the expense of Bifidobacterium and Streptococcus. Short and long antibiotic treatment both allowed for microbiota restoration within the first six postnatal weeks. However, Enterococcus and Bifidobacterium abundances were affected in fewer ST than LT infants. Conclusions Intravenous amoxicillin/ceftazidime administration affects intestinal microbiota composition by decreasing the relative abundance of Escherichia-Shigella and Streptococcus, while increasing the relative abundance of Enterococcus and Lactobacillus species during the first two postnatal weeks. Thriving of enterococci at the expense of bifidobacteria and streptococci should be considered as aspect of the cost-benefit determination for antibiotic prescription.

Antibiotic treatment is common practice in the neonatal ward for the prevention and treatment of sepsis, which is one of the leading causes of mortality and morbidity in preterm infants. Although the effect of antibiotic treatment on microbiota development is well recognised, little attention has been paid to treatment duration. We studied the effect of short and long intravenous antibiotic administration on intestinal microbiota development in preterm infants. Faecal samples from 15 preterm infants (35 ± 1 weeks gestation and 2871 ± 260 g birth weight) exposed to no, short (≤ 3 days) or long (≥ 5 days) treatment with amoxicillin/ceftazidime were collected during the first six postnatal weeks. Microbiota composition was determined through 16S rRNA gene sequencing and by quantitative polymerase chain reaction (qPCR). Short and long antibiotic treat ment significantly lowered the abundance of Bifidobacterium right after treatment (p = 0.027) till postnatal week three (p = 0.028). Long treatment caused Bifidobacterium abundance to remain decreased till postnatal week six (p = 0.009). Antibiotic treatment was effective against members of the Enterobacteriaceae family, but allowed Enterococcus to thrive and remain dominant for up to two weeks after antibiotic treatment discontinuation. Community richness and diversity were not affected by antibiotic treatment, but were positively associated with postnatal age (p < 0.023) and with abundance of Bifidobacterium (p = 0.003). Intravenous antibiotic administration during the first postnatal week greatly affects the infant’s gastrointestinal microbiota. However, quick antibiotic treatment cessation allows for its recovery. Disturbances in microbiota development caused by short and, more extensively, by long antibiotic treatment could affect healthy development of the infant via interference with maturation of the immune system and gastrointestinal tract.

Objective: Development of the gastrointestinal tract and immune system can be modulated by the gut microbiota. Establishment of the intestinal microbiota, in its turn, is affected by host and environmental factors. As such, development of the gut microbiota is greatly impacted in preterm infants, who have an immature gut and are exposed to factors like hospitalization, caesarean section, antibiotics, and respiratory support. Design: We analyzed fecal microbiota composition and activity of ten preterm infants (gestational age 25-30 weeks; birthweight 630-1750 g) during the first six postnatal weeks through metaproteomics (LC-MS/MS) and 16S-rRNA gene sequencing. Results: A gestational-age-dependent microbial signature is observed, enabling microbiota-based differentiation between extremely preterm (25-27 weeks gestation) and very preterm (30 weeks gestation) infants. In very preterm infants, the intestinal microbiota developed toward a Bifidobacterium-dominated community and was associated with high abundance of proteins involved in carbohydrate and energy metabolism. Extremely preterm infants remained predominantly colonized by facultative anaerobes and were associated with proteins involved in membrane transport and translation. Delayed colonization by obligate anaerobes could be associated with antibiotic treatment and respiratory support. Conclusion: We speculate that gestational age and its associated intensity of care (e.g. antibiotics and respiratory support) affects intestinal microbiota composition and activity in preterm infants. As the gut microbiota plays a major role in development of the neonate, gestational age and its associated factors could set the stage for early and later life health complications via interference with microbiota development.

Microbial colonization of the gastrointestinal tract is an essential process that modulates host physiology and immunity. Recently, researchers have begun to understand how and when these microorganisms colonize the gut and the earlylife factors that impact their natural ecological establishment. The vertical transmission of maternal microbes to the offspring is a critical factor for host immune and metabolic development. Increasing evidence also points to a role in the wiring of the gut-brain axis. This process may be altered by various factors such as mode of delivery, gestational age at birth, the use of antibiotics in early life, infant feeding, and hygiene practices. In fact, these early exposures that impact the intestinal microbiota have been associated with the development of diseases such as obesity, type 1 diabetes, asthma, allergies, and even neurodevelopmental disorders. The present review summarizes the impact of cesarean birth on the gut microbiome and the health status of the developing infant and discusses possible preventative and restorative strategies to compensate for early-life microbial perturbations.

To study the effect of the duration of antibiotic treatment on intestinal microbiota development during the first six postnatal weeks in late-preterm infants through 454 pyrosequencing of the 16S rRNA gene. Total of 96 samples., To study the effect of the duration of antibiotic treatment on intestinal microbiota development during the first six postnatal weeks in late-preterm infants through 454 pyrosequencing of the 16S rRNA gene. Total of 96 samples.

Development of the gut microbiota is greatly impacted in preterm infants, who have an immature gut and are exposed to factors like hospitalisation, caesarean section, antibiotics, and respiratory support. Exposure to these factors increases with decreasing gestational age and could lead to divergent microbiota development between infants of varying GA. We analysed faecal microbiota composition of ten preterm infants during the first six postnatal weeks through 16S-rRNA gene sequencing., Development of the gut microbiota is greatly impacted in preterm infants, who have an immature gut and are exposed to factors like hospitalisation, caesarean section, antibiotics, and respiratory support. Exposure to these factors increases with decreasing gestational age and could lead to divergent microbiota development between infants of varying GA. We analysed faecal microbiota composition of ten preterm infants during the first six postnatal weeks through 16S-rRNA gene sequencing.

Preterm birth interrupts normal fetal growth with consequences for postnatal growth and organ development. In preterm infants, many physiological deficits adapt and disappear with advancing postnatal age, but some may persist into childhood. We hypothesized that preterm birth would induce impaired organ growth and function during the first postnatal week in pigs, while motor abilities and behavioral characteristics would show more persistent developmental delay. Cesarean-delivered preterm (n = 112, 90% gestation) or term (n = 56, 100% gestation) piglets were reared under identical conditions and euthanized for blood and organ collection on postnatal days 0, 5, or 26. Body weight gain remained lower in preterm vs. term pigs up to day 26 (25.5 ± 1.5 vs. 31.0 ± 0.5 g·kg(-1)·day(-1), P < 0.01) when relative weights were higher for brain and kidneys and reduced for liver and spleen. Neonatal preterm pigs had reduced values for blood pH, Po2, glucose, lactate, hematocrit, and cortisol, but at day 26, most values were normalized, although plasma serotonin and IGF 1 levels remained reduced. Preterm pigs showed delayed neonatal arousal and impaired physical activity, coordination, exploration, and learning, relative to term pigs (all P < 0.05). Supplementation of parenteral nutrition during the first 5 days with an enteral milk diet did not affect later outcomes. In preterm pigs, many physiological characteristics of immaturity disappeared by 4 wk, while some neurodevelopmental deficits remained. The preterm pig is a relevant animal model to study early dietary and pharmacological interventions that support postnatal maturation and neurodevelopment in preterm infants.

Introduction The colonic mucus layer plays an important role in the protection of the intestinal epithelium and mainly consists of mucin glycoproteins (primarily MUC2 in the colon) trefoil factor 3 (TFF3) and secretory IgA. Butyrate is a major end product of fermentation of dietary fibres and is associated with beneficial effects on colonic health. Earlier in-vitro and animal studies showed that butyrate modulates MUC2 and TFF3 expression and mucin secretion, although data from human studies are not yet available. Methods Sixteen healthy volunteers and 35 ulcerative colitis (UC) patients in clinical remission self-administered a 60 ml rectal enema containing 100 mmol/l butyrate or placebo once daily for 2 and 3 weeks, respectively. After each treatment, biopsies were taken from the distal sigmoid for quantitative RT-PCR and immunohistochemical analysis of MUC2 and TFF3. In addition, mucosal sections were stained with high iron diamine-alcian blue to distinguish between sialomucins and sulphomucins. To analyse total mucin secretion and secretory IgA concentrations, 24 h faeces were collected during the day before the endoscopic examination. Results The butyrate intervention did not significantly modulate the expression of MUC2 ( fold change: 1.04 and 1.05 in healthy volunteers and ulcerative colitis patients, respectively) or TFF3 (fold change: 0.91 and 0.94 in healthy volunteers and UC patients, respectively). Furthermore, the percentage of sialomucins, mucus secretion and secretory IgA concentrations were not affected by the butyrate intervention in both the groups. Conclusion Butyrate exposure in healthy volunteers and UC patients in remission did not affect the measured parameters of the colonic mucus layer. Eur J Gastroenterol Hepatol 22: 1134-1140 (C) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.