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



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.



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.



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.



ClinicalTrials.gov: NCT01756040.
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD.
Bushra
B
Saleem
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD.
Adora C
AC
Okogbule-Wonodi
MassGeneral Hospital for Children, Center for Celiac Research and Treatment, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, MA.
Alessio
A
Fasano
Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD.
Laurence S
LS
Magder
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD; Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD.
Jacques
J
Ravel
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD.
Shiv
S
Kapoor
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD.
Rose M
RM
Viscardi
D000704:Analysis of Variance; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D002657:Child Development / Q000502:physiology; D005248:Feeding Methods; D005260:Female; D005500:Follow-Up Studies; D005865:Gestational Age; D006801:Humans; D007223:Infant; D041943:Infant Formula; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000378:metabolism*; D007408:Intestinal Absorption / Q000502:physiology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007785:Lactose / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008895:Milk, Human / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D011446:Prospective Studies; D012210:Rhamnose / Q000008:administration & dosage / Q000493:pharmacokinetics
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D007785:Lactose; D012210:Rhamnose
alpha-1-anti-trypsin; intestinal permeability; prematurity; zonulin