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Intestinal Barrier Maturation in Very Low Birthweight Infants: Relationship to Feeding and Antibiotic Exposure.

ABSTRACT: OBJECTIVE:To test the hypothesis that feeding and antibiotic exposures affect intestinal barrier maturation in preterm infants, we serially measured intestinal permeability (IP) biomarkers in infants <33?weeks gestation (gestational age [GA]) during the first 2 weeks of life. STUDY DESIGN:Eligible infants <33?weeks GA were enrolled within 4 days of birth in a prospective study of IP biomarkers (NCT01756040). Study participants received the nonmetabolized sugars lactulose/rhamnose enterally on study days 1, 8, and 15 and lactulose/rhamnose were measured in urine by high-performance liquid chromatography. Serum zonulin and fecal alpha-1-anti-trypsin, 2 other IP markers, were measured by semiquantitative Western blot and ELISA, respectively. RESULTS:In a cohort of 43 subjects, the lactulose/rhamnose ratio was increased on day 1 and decreased over 2 weeks, but remained higher in infants born at ?28?weeks of gestation compared with IP in infants born at >28?weeks of gestation. Exclusive breastmilk feeding was associated with more rapid maturation in intestinal barrier function. A cluster analysis of 35 subjects who had urine samples from all time points revealed 3 IP patterns (cluster 1, normal maturation: n?=?20 [57%]); cluster 2, decreased IP during the first week and subsequent substantial increase: n?=?5 [14%]); and cluster 3, delayed maturation: n?=?10 [29%]). There were trends toward more prolonged antibiotic exposure (P?=?.092) and delayed initiation of feeding ?4 days (P?=?.064) in infants with abnormal IP patterns. CONCLUSIONS:Intestinal barrier maturation in preterm infants is GA and postnatal age dependent, and is influenced by feeding with a maturational effect of breastmilk feeding and possibly by antibiotic exposures. TRIAL REGISTRATION:ClinicalTrials.gov: NCT01756040.

SUBMITTER: Saleem B

PROVIDER: S-EPMC5367935 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Intestinal Barrier Maturation in Very Low Birthweight Infants: Relationship to Feeding and Antibiotic Exposure.

Saleem Bushra B Okogbule-Wonodi Adora C AC Fasano Alessio A Magder Laurence S LS Ravel Jacques J Kapoor Shiv S Viscardi Rose M RM

The Journal of pediatrics 20170131

<h4>Objective</h4>To test the hypothesis that feeding and antibiotic exposures affect intestinal barrier maturation in preterm infants, we serially measured intestinal permeability (IP) biomarkers in infants <33 weeks gestation (gestational age [GA]) during the first 2 weeks of life.<h4>Study design</h4>Eligible infants <33 weeks GA were enrolled within 4 days of birth in a prospective study of IP biomarkers (NCT01756040). Study participants received the nonmetabolized sugars lactulose/rhamnose ...[more]

PMID: 28159311

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Project description:BackgroundOptimal feeding of very low birthweight (VLBW <1500 g)/very preterm (gestation <32 weeks) infants in resource-limited settings in sub-Saharan Africa (sSA) is critical to reducing high mortality and poor outcomes.ObjectiveTo review evidence on feeding of VLBW/very preterm infants relevant to sSA.MethodsWe searched the Cochrane Database of Systematic Reviews, Embase, PubMed and Cumulative Index to Nursing and Allied Health Literature (CINAHL) from inception to July 2019 to identify reviews of randomised and quasi-randomised controlled trials of feeding VLBW/very preterm infants. We focused on interventions that are readily available in sSA. Primary outcomes were weight gain during hospital stay and time to achieve full enteral feeds (120 mL/kg/day). Secondary outcomes were growth, common morbidities, mortality, duration of hospital stay and cognitive development. Quality of evidence (QOE) was assessed using the Measurement Tool to Assess Systematic Reviews (AMSTAR2).ResultsEight systematic reviews were included. Higher feed volume of day 1 (80 mL/kg) reduced late-onset sepsis and time to full enteral feeds, and higher feed volume (up to 300 mL/kg/day) improved weight gain without adverse events (QOE: low-moderate). Rapid advancement of feeds (30-40 mL/kg/day) was not associated with harm. Breast milk fortification with energy and protein increased growth and with prebiotics increased growth and reduced duration of admission (QOE: low-very low) and did not result in harm. Evidence regarding feeding tube placement and continuous versus bolus feeds was insufficient to draw conclusions. We found no reviews meeting our selection criteria regarding when to start feeds, use of preterm formula, cup-and-spoon feeding or gravity versus push feeds and none of the reviews included trials from low-income countries of sSA.ConclusionsThe evidence base informing feeding of VLBW/very preterm babies in resource-limited settings in sSA is extremely limited. Pragmatic studies are needed to generate evidence to guide management and improve outcomes for these highly vulnerable infants.Prospero registration numberCRD42019140204.

Project description:"Leaky gut," or high intestinal barrier permeability, is common in preterm newborns. The role of the microbiota in this process remains largely uncharacterized. We employed both short- and long-read sequencing of the 16S rRNA gene and metagenomes to characterize the intestinal microbiome of a longitudinal cohort of 113 preterm infants born between 240/7 and 326/7 weeks of gestation. Enabled by enhanced taxonomic resolution, we found that a significantly increased abundance of Bifidobacterium breve and a diet rich in mother's breastmilk were associated with intestinal barrier maturation during the first week of life. We combined these factors using genome-resolved metagenomics and identified a highly specialized genetic capability of the Bifidobacterium strains to assimilate human milk oligosaccharides and host-derived glycoproteins. Our study proposes mechanistic roles of breastmilk feeding and intestinal microbial colonization in postnatal intestinal barrier maturation; these observations are critical toward advancing therapeutics to prevent and treat hyperpermeable gut-associated conditions, including necrotizing enterocolitis (NEC). IMPORTANCE Despite improvements in neonatal intensive care, necrotizing enterocolitis (NEC) remains a leading cause of morbidity and mortality. "Leaky gut," or intestinal barrier immaturity with elevated intestinal permeability, is the proximate cause of susceptibility to NEC. Early detection and intervention to prevent leaky gut in "at-risk" preterm neonates are critical for decreasing the risk of potentially life-threatening complications like NEC. However, the complex interactions between the developing gut microbial community, nutrition, and intestinal barrier function remain largely uncharacterized. In this study, we reveal the critical role of a sufficient breastmilk feeding volume and the specialized carbohydrate metabolism capability of Bifidobacterium in the coordinated postnatal improvement of the intestinal barrier. Determining the clinical and microbial biomarkers that drive the intestinal developmental disparity will inform early detection and novel therapeutic strategies to promote appropriate intestinal barrier maturation and prevent NEC and other adverse health conditions in preterm infants.

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Intestinal Barrier Maturation in Very Low Birthweight Infants: Relationship to Feeding and Antibiotic Exposure.

Publications

Intestinal Barrier Maturation in Very Low Birthweight Infants: Relationship to Feeding and Antibiotic Exposure.

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