Differences in Polyamine Content between Human Milk and Infant Formulas

Human milk is the gold standard for nutrition during the first months of life, but when breastfeeding is not possible, it may be replaced by infant formulas, either partially or totally. Polyamines, which play an important role in intestinal maturation and the development of the immune system, are found both in human milk and infant formulas, the first exogenous source of these compounds for the newborn. The aim of this study was to evaluate the occurrence and evolution of polyamines in human milk during the first semester of lactation and to compare the polyamine content with that of infant formulas. In total, 30 samples of human milk provided by six mothers during the first five months of lactation as well as 15 different types of infant formulas were analyzed using UHPLC-FL. Polyamines were detected in all human milk samples but with great variation among mothers. Spermidine and spermine levels tended to decrease during the lactation period, while putrescine remained practically unchanged. Considerable differences were observed in the polyamine contents and profiles between human milk and infant formulas, with concentrations being up to 30 times lower in the latter. The predominant polyamines in human milk were spermidine and spermine, and putrescine in infant formulas.

Evolution of Thyroid Enhancement of Embryogenesis and Early Survival

Iodine imparts protective antioxidant actions that improve the fitness of invertebrate organisms, and peptides carrying iodine initially appear to have served in a defensive capacity. Tyrosine carries multiple iodines in some echinoderms, and these peptides transferred to progeny serve both protective and signaling purposes. This parental relationship appears to be the most likely evolutionary basis for emergence of the vertebrate thyroid endocrine system, and its critically important development-promoting actions in larval and (later) fetal ontogeny. Thyroxine (T4) and Triiodothyronine (T3) induce settlement and stimulate transitions to alternative feeding modes in some echinoderms. This transgenerational relationship has been conserved and elaborated in vertebrates, including humans, which share common ancestry with echinoderms. Thyroid insufficiency is damaging or can be lethal to larval fishes; egg yolk that is insufficiently primed with maternal thyroid hormones (TH) results in compromised development and high mortality rates at the time of first-feeding. Maternally-derived TH supplied to offspring supports the onset of independent feeding in fishes (eye, mouth, lateral line, swim bladder and intestinal maturation) and survival by comparable developmental mechanisms in placental mammals. Fishes evolved precise control of TH secretion and peripheral processing; early metamorphic and feeding mode actions were joined by controlled thermogenesis in homeotherms.

Intra-Amniotic Administration of l-Glutamine Promotes Intestinal Maturation And Enteroendocrine Stimulation In Chick Embryos

Initial nutritional stimulation is a key driving force for small intestinal maturation, and is mediated by enteroendocrine L-cells signaling. In chick embryos, administration of specific nutrients into the amniotic fluid stimulates early development of the small intestine. In this study, we examined the effects of intra-amniotic administration of l-glutamine (Gln) on enterocyte morphological and functional maturation and L-cell signaling before and after hatch. Gln stimulation at embryonic day 17 caused an increase in enterocyte and microvilli dimensions by 10 and 20%, respectively, within 48h. Post-hatch, enterocytes and microvilli were 20% longer in Gln-treated chicks. Correspondingly, mRNA expression of brush border nutrient transporters PepT-1 and SGLT-1 and tight junction proteins TJP-1, TJP-2 and Occludin was significantly upregulated before and after hatch (P<0.05) in Gln-treated chicks. We then evaluated the effects of Gln stimulation on enteroendocrine signaling by locating L-cells in the developing jejunum and observed significant increases in mRNA expression of L-cell signaling components GLP-2R, IGF-1 and IGF-1R before and after hatch, in response to Gln stimulation (P<0.05). Our findings link primary nutrient stimulation of L-cells to enterocyte morphological and functional maturation and provide a model for investigating the effects of specific nutrients on enteroendocrine signaling in the developing small intestine.

Oral Spermine Supplementation in Gestated Rabbit: A Study on Villi Height of Immature Intestines

Introduction: Immature intestines are the major problem in prematurity. Postnatal oral spermine has been shown in studies to improve intestinal maturation in rats and piglets. This study aimed to find out the efficacy of spermine in rabbits during gestation.Method: An experimental study was done in an unblinded, randomized manner on those treated with and without spermine administration. A morphological examination of hematoxylin–eosin-stained villi was performed under a light microscope with a focus on villi height. Data were subjected to analysis.Results: The median of the spermine-treated group was found to be higher at 24, 26, and 28 days than the non-spermine group, but was not significantly different.Conclusion: Oral spermine supplementation during gestation might improve intestinal villi height in immature rabbit intestines.

Investigation of Early Supplementation of Nucleotides on the Intestinal Maturation of Weaned Piglets

Nucleotides are essential for the development of the gastrointestinal tract and immune function, but their intake with milk by piglets could be insufficient. The effect of nucleotides on growth and health was tested on 98 piglets divided into two groups: NU, orally administrated with 4 mL of a nucleotide-based product (SwineMOD®) at 10, 15, 18, 21, 27 days, or not (CO). Blood and feces were sampled at weaning (26 d, T1), and at 38 d (T2). Per each group and time-point, eight piglets were slaughtered and jejunal Peyer’s patches (JPPs) were collected. NU increased hemoglobin content and hematocrit, but not growth. At weaning, the NU fecal microbiota was characterized by the abundance of Campylobacteraceae, more typical of the growing phase, compared to CO, with a greater abundance of Streptococcaceae. For the blood transcriptome, an initial greater inflammatory activation was seen in CO, while at T2, NU enriched gene sets related to erythropoiesis. The activation of gene groups ranging from epigenetic response to transcriptional regulation evidenced an intense proliferative activity in NU JPPs. NU supplementation did not influence the growth performance of piglets but could have expressed a positive effect on pig microbiota anticipating its maturation at weaning. This immunostimulant activity in the JPPs could moderate the inflammation in the immediate pre-weaning.

Serum ghrelin is associated with early feeding readiness but not growth in premature infants

BACKGROUND: Feeding tolerance among premature infants is unpredictable using clinical parameters. Ghrelin, a peptide hormone, acts on the hypothalamus to increase hunger and gut motility. It is present in fetal tissues, promotes intestinal maturation, and is secreted in milk. We hypothesized that higher serum ghrelin levels on days 0–7 are associated with improved feeding tolerance and growth in premature infants. METHODS: Infants (< 1500 g birth weight, n = 36) were recruited on day (D) 0–7. Serum ghrelin was measured by ELISA on D 0–7, D 10–14, and D 24–32, and milk ghrelin in a feeding concurrent with each serum sample. Feeding tolerance was assessed as days to first and full enteral feeds. Growth was quantified as both weight and adipose and muscle deposition by ultrasound. RESULTS: Mean serum ghrelin levels decreased from D 0–7 to D 24–32. Higher ghrelin levels on D 0–7 were correlated with shorter time to first enteral feeding, but not with time to full enteral feeds, rate of weight gain, or rate of accretion of muscle or adipose tissue. Milk ghrelin was not related to serum ghrelin or growth. Abdominal and suprascapular muscle and adipose increased during the first month, but weight gain correlated only with the rate of accretion of abdominal adipose. CONCLUSIONS: Elevated serum ghrelin in the first days of life may contribute to gut motility and readiness to feed. Weight gain in premature infants may primarily indicate abdominal fat accumulation, suggesting that ultrasound measurement of muscle accretion is a better marker for lean body growth.

It’s All About Timing: Early Feeding Promotes Intestinal Maturation by Shifting the Ratios of Specialized Epithelial Cells in Chicks

The small intestine (SI) of chicks (Gallus gallus) matures rapidly during the initial post-hatch period and acquires digestive, absorptive, and secretive capabilities. The effects of the timing of first feeding on the quantities and distribution of specialized epithelial cells, which generate and maintain SI morphology and functionality, have not yet been examined. In this study, we identified specialized SI epithelial cell sub-types, including stem, progenitor, proliferating, and differentiated cells within crypts and villi of chicks during the first 10 days post-hatch, by in situ hybridization (ISH), immunofluorescence (IF), and histochemical staining. We then examined their quantities and ratios between day of hatch and d10 in chicks that were fed upon hatch [early feeding (EF)], compared to chicks that were fed 24 h post-hatch [delayed feeding (DF)]. Results showed that EF increased total cell quantities in the crypts and villi at days 1, 3, 7, and 10, compared to DF (p &lt; 0.0001). At d3, EF, in comparison to DF, decreased crypt stem cell proportions (p &lt; 0.0001), increased crypt proliferating (p &lt; 0.01) and differentiated (p &lt; 0.05) cell proportions, and increased villus enterocyte proportions (p &lt; 0.01). By d10, EF increased both the quantities and proportions of villus enterocytes and goblet cells, compared to DF. We conclude that feeding upon hatch, compared to 24 h-delayed feeding, enhanced SI maturation and functionality by increasing the quantities and proportions of proliferating and differentiated cells, thus expanding the digestive, absorptive, and secretive cell populations throughout the initial post-hatch period.

Perinatal environment shapes microbiota colonization and infant growth: impact on host response and intestinal function

Background Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods Gut microbiota profile of 180 healthy infants (n = 23 born at home and n = 157 born in hospital, 41.7% via cesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, 7 days, and 1 month of life. Breastfeeding habits and infant clinical data, including length, weight, and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function, and immune response. Results Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier, and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants. Trial registration NCT03552939.

Perinatal Environment Shapes Microbiota Colonization And Infant Growth: Impact On Host Response And Intestinal Function

Background: Early microbial colonization triggers processes that result in intestinal maturation and immune priming. Perinatal factors, especially those associated with birth, including both mode and place of delivery are critical to shaping the infant gut microbiota with potential health consequences. Methods: Gut microbiota profile of 180 healthy infants (n=23 born at home and n=157 born in hospital, 41.7% via caesarean section [CS]) was analyzed by 16S rRNA gene sequencing at birth, seven days and one month of life. Breastfeeding habits, infant clinical data, including length, weight and antibiotic exposure, were collected up to 18 months of life. Long-term personalized in vitro models of the intestinal epithelium and innate immune system were used to assess the link between gut microbiota composition, intestinal function and immune response. Results: Microbiota profiles were shaped by the place and mode of delivery, and they had a distinct biological impact on the immune response and intestinal function in epithelial/immune cell models. Bacteroidetes and Bifidobacterium genus were decreased in C-section infants, who showed higher z-scores BMI and W/L during the first 18 months of life. Intestinal simulated epithelium had a stronger epithelial barrier function and intestinal maturation, alongside a higher immunological response (TLR4 route activation and pro-inflammatory cytokine release), when exposed to home-birth fecal supernatants, compared with CS. Distinct host response could be associated with different microbiota profiles. Conclusions: Mode and place of birth influence the neonatal gut microbiota, likely shaping its interplay with the host through the maturation of the intestinal epithelium, regulation of the intestinal epithelial barrier and control of the innate immune system during early life, which can affect the phenotypic responses linked to metabolic processes in infants.