Maturation Of Gastrointestinal Tract Research Articles

Development of early life gut resistome and mobilome across gestational ages and microbiota-modifying treatments.

Gestational age (GA) and associated level of gastrointestinal tract maturation are major factors driving the initial gut microbiota composition in preterm infants. Besides, compared to term infants, premature infants often receive antibiotics to treat infections and probiotics to restore optimal gut microbiota. How GA, antibiotics, and probiotics modulate the microbiota's core characteristics, gut resistome and mobilome, remains nascent. We analysed metagenomic data from a longitudinal observational study in six Norwegian neonatal intensive care units to describe the bacterial microbiota of infants of varying GA and receiving different treatments. The cohort consisted of probiotic-supplemented and antibiotic-exposed extremely preterm infants (n=29), antibiotic-exposed very preterm (n=25), antibiotic-unexposed very preterm (n=8), and antibiotic-unexposed full-term (n=10) infants. The stool samples were collected on days of life 7, 28, 120, and 365, and DNA extraction was followed by shotgun metagenome sequencing and bioinformatical analysis. The top predictors of microbiota maturation were hospitalisation length and GA. Probiotic administration rendered the gut microbiota and resistome of extremely preterm infants more alike to term infants on day 7 and ameliorated GA-driven loss of microbiota interconnectivity and stability. GA, hospitalisation, and both microbiota-modifying treatments (antibiotics and probiotics) contributed to an elevated carriage of mobile genetic elements in preterm infants compared to term controls. Finally, Escherichia coli was associated with the highest number of antibiotic-resistance genes, followed by Klebsiella pneumoniae and Klebsiella aerogenes. Prolonged hospitalisation, antibiotics, and probiotic intervention contribute to dynamic alterations in resistome and mobilome, gut microbiota characteristics relevant to infection risk. Odd-Berg Group, Northern Norway Regional Health Authority.

Correlation of umbilical cord arterial blood pH with meconium stained liquor

Intrauterine passage of meconium may be due to fetal hypoxia, or it may simply indicate a normal gastrointestinal tract maturation. Umbilical cord blood pH is the best available criterion for detecting fetal hypoxia and making appropriate decisions about care after birth.To determine the correlation of umbilical cord arterial blood pH with meconium stained liquor and neonatal outcome. To determine whether the mode of delivery had any influence on the occurrence of acidemia in the neonate complicated with meconium stained liquor. A prospective observational study was conducted for a period of 6 months. Immediately following delivery in pregnancies complicated with meconium stained liquor, blood was drawn from the umbilical artery and sent for arterial blood gas (ABG) analysis. Neonatal outcome parameters and mode of delivery were then recorded in a pre-designed proforma. There was a statistically significant correlation between abnormal pH (acidosis) and thick meconium stained liquor. Neonatal outcome parameters like Apgar scores at 1 minute and 5 minutes, intravenous antibiotic administration, NICU admission and oxygen supplementation were statistically significant when correlated with the pH level.The degree of meconium thickness independently correlates with the composite adverse neonatal outcome. Cases with meconium stained liquor should be monitored vigorously with timely interventions and proper neonatal resuscitation, especially the ones with thick meconium stained liquor, in order to prevent adverse neonatal outcome.

Prediction of Perinatal Outcome with Meconium-stained Liquor

Background & objective: Passage of meconium in the amniotic fluid during labor has long been considered as fetal compromise resulting from fetal hypoxia or increased vagal activity from cord compression. It is also a sign of normal gastrointestinal tract maturation under neuronal control. However, presence of meconium in the amniotic fluid is traditionally viewed as unfavorable perinatal outcome. So, the present study was contemplated to find the association between grade of meconium during labor and perinatal outcome.
 Methods: The present prospective study was conducted in the North Bengal Medical College, Sirajganj between January 2016 – April 2017. Based on predefined criteria, 53 singleton pregnant women with meconium-stained liquor (MSL) on spontaneous or artificial rupture of membrane after 37 completed weeks of gestation were included in the study. Meconium-stained liquor was graded as “Thick” if the fluid was dark green in colour, viscous, tenacious, opalescent or opaque containing large amount of particulate materials and “Thin” if the fluid was translucent, light yellow green in colour without particulate material. The perinatal outcome was evaluated in terms of APGAR score of neonates at 1 and at 5 minutes of birth, NICU admission, resuscitation needed, jaundice and respiratory distress syndrome (RDS) due to meconium aspiration. Asphyxia neonatorum was diagnosed if APGAR at birth and/or at 5 minutes was < 7. All the outcomes were then compared between mothers forming ‘Thick’ and ‘Thin’ meconium cohort.
 Result: Of the 53 meconium-stained liquor, nearly half (49%) was with ‘Thick’ meconium and the half (51%) was with ‘Thin’ meconium. Approximately 85% of the neonates were delivered by lower uterine caesarean section (LUCS) and 80% of the neonates were asphyxiated at birth which reduced to 15.1% at 5 minutes. More than three-quarters (75.5%) of the neonates required resuscitation and 28.3% had respiratory distress syndrome (RDS). The incidences of asphyxia neonatorum, resuscitation needed and RDS were significantly higher in ‘Thick’ meconium cohort than those in ‘Thin’ meconium cohort with risks of having these conditions in the former cohort being 6(95% CI = 1.1–31.2), 4.5(95% CI = 1.1–18.9) and 4.2(95% CI = 1.1–15.7) times higher respectively than those in the latter cohort (p = 0.021, p = 0.031 and p = 0.026 respectively).
 Conclusion: Majority of the neonates born of mothers with thick meconium cohort are asphyxiated, need resuscitation and/or develop RDS. Asphyxia neonatorum, need for resuscitation and RDS are significantly higher in ‘Thick’ meconium cohort than those in ‘Thin’ meconium cohort with risks of having these conditions in the former cohort being several times higher than those in the latter cohort.
 Ibrahim Card Med J 2019; 9 (1&2): 67-73

Perinatal hormones favor CC17 group B Streptococcus intestinal translocation through M cells and hypervirulence in neonates.

Group B Streptococcus (GBS) is the leading cause of invasive bacterial neonatal infections. Late-onset diseases (LOD) occur between 7 and 89 days of life and are largely due to the CC17 GBS hypervirulent clone. We studied the impact of estradiol (E2) and progesterone (P4), which impregnate the fetus during pregnancy, on GBS neonatal infection in cellular and mouse models of hormonal exposure corresponding to concentrations found at birth (E2-P4 C0) and over 7 days old (E2-P4 C7). Using representative GBS isolates, we show that E2-P4 C7 concentrations specifically favor CC17 GBS meningitis following mice oral infection. CC17 GBS crosses the intestinal barrier through M cells. This process mediated by the CC17-specific surface protein Srr2 is enhanced by E2-P4 C7 concentrations which promote M cell differentiation and CC17 GBS invasiveness. Our findings provide an explanation for CC17 GBS responsibility in LOD in link with neonatal gastrointestinal tract maturation and hormonal imprint.

PROTOCOL: Efficacy and effectiveness of micronutrient supplementation and fortification interventions on the health and nutritional status of children under-five in low and middle-income countries: a systematic review.

PROTOCOL: Efficacy and effectiveness of micronutrient supplementation and fortification interventions on the health and nutritional status of children under-five in low and middle-income countries: a systematic review.

Amniotic fluid: Source of trophic factors for the developing intestine

The gastrointestinal tract (GIT) is a complex system, which changes in response to requirements of the body. GIT represents a barrier to the external environment. To achieve this, epithelial cells must renew rapidly. This renewal of epithelial cells starts in the fetal life under the influence of many GIT peptides by swallowing amniotic fluid (AF). Development and maturation of GIT is a very complex cascade that begins long before birth and continues during infancy and childhood by breast-feeding. Many factors like genetic preprogramming, local and systemic endocrine secretions and many trophic factors (TF) from swallowed AF contribute and modulate the development and growth of the GIT. GIT morphogenesis, differentiation and functional development depend on the activity of various TF in the AF. This manuscript will review the role of AF borne TF in the development of GIT.

Apelin's effects on young rat gastrointestinal tract maturation

Apelin is considered an important gut regulatory peptide with potential physiological roles in gastrointestinal cytoprotection and regulation of food intake and drinking behavior. The aim of this study was to determine the effects of intraperitoneal or intragastric apelin administration on gastric and intestinal epithelial apoptosis, mitosis and DNA repair enzyme 8-oxoguanine (OGG 1/2) expression in young Wistar rats (50±5gb.wt.). Apelin-13 was intraperitoneally or intragastrically administered twice a day for 10 days (100nmol/kgb.wt./2×day), and control groups received physiological saline as a placebo. The rats were sacrificed after treatment, and the gastric fundus, duodenum, middle jejunum and colon tissue samples were harvested for immunofluorescence studies. Intragastric administration of apelin-13 increased the apoptotic index in the stomach and colon tissues (P≤0.001) but decreased apoptosis in the duodenum and jejunum (P<0.001); this approach reduced the number of mitotic cells in the jejunum and colon but increased mitoses (P<0.001) in the duodenum. Finally, intragastric apelin-13 increased (P<0.001) OGG 1/2 enzyme expression in the stomach and jejunum and decreased its expression in the colon (P<0.01). However, intraperitoneal apelin-13 injection caused the opposite effect in the same regions of the gastrointestinal tract. In conclusion, apelin inhibits gastrointestinal tissue maturation in young rats, regardless of the administration route. However, further studies are required to clarify the mechanism of apelin action on gastrointestinal tract maturation in young rats.

Human Milk Oligosaccharides Influence Maturation of Human Intestinal Caco-2Bbe and HT-29 Cell Lines

Stimulation of gastrointestinal tract maturation is 1 of the many benefits of human milk. Human milk oligosaccharides (HMOs) are abundant in human milk and are reported to promote enterocyte differentiation in vitro. The objective of this study was to assess the impact of 3 predominant HMOs on multiple aspects of enterocyte maturation in vitro. Ranging from crypt-like to differentiated enterocytes, we used the well-characterized intestinal cell lines HT-29 and Caco-2Bbe to model early and late stages of differentiation, respectively. With this model of the crypt–villus axis made up of preconfluent HT-29, preconfluent Caco-2Bbe, and postconfluent Caco-2Bbe cultures, we characterized the impact of lacto-N-neotetraose (LNnT), 2′-fucosyllactose (2′FL), and 6′-sialyllactose on epithelial cell kinetics and function. All 3 HMOs dose-dependently inhibited cell proliferation in undifferentiated HT-29 and Caco-2Bbe cultures (P < 0.05). In contrast to previous reports, only treatment with 2′FL at concentrations similar to human milk increased alkaline phosphatase activity by 31% (P = 0.044) in HT-29 cultures and increased sucrase activity by 54% (P = 0.005) in well-differentiated Caco-2Bbe cultures. LNnT at concentrations similar to that reported for human milk increased transepithelial resistance by 21% (P = 0.002) in well-differentiated Caco-2Bbe cells. In summary, all 3 HMOs reduced cell proliferation in an epithelial cell model of the crypt–villus axis. However, effects on differentiation, digestive function, and epithelial barrier function differed between the HMOs tested. These results suggest differential roles for specific HMOs in maturation of the gastrointestinal tract.

The effect of desiccated ox bile supplementation on performance, fat digestibility, gut morphology and blood chemistry of broiler chickens fed tallow diets

An experiment was conducted to study the effects of different dietary levels of desiccated ox bile on the performance, fat digestibility, gut morphology and blood variables of broiler chickens fed tallow diet. One hundred and fifty one-day-old male broilers (Ross 308) were equally distributed into three treatments (with five replicates each) in a completely randomised design. Desiccated ox bile was added to the experimental diets during starter (7–21 day) and grower (22–42 day) periods (0.00, 0.25 and 0.50% of diet). During the experiment, the measured parameters were average body weight gain, average feed intake, average feed conversion ratio, gut morphology, serum cholesterol (Chol), triglyceride, high density lipoprotein and low density lipoprotein. During the grower and overall periods, ABWG and AFCR were significantly improved (p<0.05). Dietary supplementation of desiccated ox bile in the diet resulted in significant (p<0.05) linear increase in fat digestibility ranged from 51% (0.00% desiccated ox bile in the diet) to 84% (0.50% desiccated ox bile in the diet). Dietary desiccated ox bile supplementation increased (p<0.05) villus height, crypt depth, villus width and villus apparent surface area in the jejunum and ileum. The results of this study indicated that dietary desiccated ox bile can be used as a natural non-nutrient additive to improve broiler performance and tallow digestibility in broiler chickens at least by stimulation of morphological maturation of gastrointestinal tract.

Ingestion of Amniotic Fluid Before Birth: Does It Improve Intestinal Function?

The structure and function of the gastrointestinal tract (GIT) matures rapidly in the period immediately before and after birth, but inadequate intestinal maturation often lead to digestive problems during this critical period. Oral milk intake is known to induce a marked GIT maturation in newborns. It is not clear whether oral intake of amniotic fluid by fetuses has a corresponding role before birth. Amniotic fluid contains both protein (1%) and a large number of growth factors and hormones. In addition, this fetal fluid possesses positive immunological properties. If amniotic fluid is important for intestinal growth and function before birth, amniotic fluid may be used to improve digestive function under certain intestinal disease conditions just after birth. Hence, we investigated the growth and functional development of the GIT in control fetal pigs throughout the last 20% of gestation (term = 115 d), and at 91% gestation in fetal pigs prevented from swallowing amniotic fluid by experimental esophageal ligation from 80-91% gestation (n=10). After killing, the GIT was collected from all fetal and newborn pigs, and the activity of digestive enzymes and absorption of nutrients were measured in vitro. The results showed that during the last 20% of gestation, marked increases occurred in body weight (+200%) and relative weight (g/kg body weight) of the small intestine (+80%). GIT function also matured rapidly during this time as assessed by significant increases in the tissue-specific activities of some digestive enzymes (1.5-10 fold) and intestinal nutrient uptakes (3-fold for glucose). Ligated fetuses showed significantly reduced body weight (-20%) and an even greater reduction of intestinal weight (-43%, P<0.05), compared with sham-operated fetuses. This was not associated with notable changes in the tissue-specific activity (units per gram wet tissue) of 10 GIT enzymes measured (chymosin, amylase, trypsin, chymotrypsin, 3 disaccharidases, 3 peptidases) or in the absorption of 5 different nutrients (glucose, leucine, lysine, proline, glycine-sarcosine). We conclude that the oral intake of amniotic fluid by the fetus is important for body growth, and especially for the growth of the small intestine. However, the enzymatic development of the GIT does not depend on oral nutrients before birth. Nevertheless, it appears that amniotic fluid is important for intestinal development in the fetus, and therefore amniotic fluid should be tested as a dietary regimen for newborn farm animals suffering from intestinal disease.

Effect of age on the intestinal absorption of vitamin D3-palmitate and nonesterified vitamin D2 in the term human infant.

This study was undertaken to investigate the utility of vitamin D3-palmitate as a nutritional supplement and thus define the intestinal absorption profile of vitamin D2 and vitamin D3 liberated after its cleavage from vitamin D3-palmitate in the human infant at various postnatal ages. The subjects for study consisted of 48 normal infants that were simultaneously administered 0.07 and 0.08 micromol/kg BW vitamin D as vitamin D3-palmitate and nonesterified vitamin D2 respectively, by orogastric tube. Blood samples were obtained before and 6, 12, and 24 h postadministration and analyzed simultaneously for vitamins D2 and D3. For data analysis, the infants were divided into two groups based on postnatal age: group 1, 1 day of age; and group 2, more than 10 days of age. Data were analyzed using the integrated peak area under the absorption curve for each subject. All subjects demonstrated the ability to absorb vitamin D after oral administration, although postnatal age as well as vitamin form had a profound effect on the absorption of vitamin D2 and vitamin D3 liberated from vitamin D3-palmitate. Nonesterified vitamin D2 is well absorbed both in very young and older infants, although absorption efficiency increases with age, perhaps due to increased bile acid secretion. Liberation of vitamin D3 from vitamin D3-palmitate was shown to increase, perhaps due to gastrointestinal tract maturation, beyond 10 days of age, probably coinciding with the secretion of intestinal esterases. Our data indicate that both forms of the orally administered vitamin approach equivalency in their abilities to elevate circulating vitamin D levels in the human infant at a postnatal age of approximately 89 days. Thus, vitamin D3-palmitate would appear not to be dietarily equivalent to free vitamin D as a nutritional source of vitamin D in the human neonate.