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

Saleem, Bushra; Okogbule-Wonodi, Adora C.; Fasano, Alessio; Magder, Laurence S.; Ravel, Jacques; Kapoor, Shiv S; Viscardi, Rose M.

doi:10.1016/j.jpeds.2017.01.013

Cited by 52 publications

(92 citation statements)

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“…The demographic, obstetric, and neonatal characteristics for all thirty-eight preterm infants enrolled in the study are summarized in Table 1 . As previously reported 16 , 20 infants (57%) experienced a rapid decrease in intestinal permeability (IP), 5 infants (14%) had a decreased IP during the first week and subsequent substantial increase and 10 infants (29%) showed a delayed IP decrease maintaining high IP throughout the study period. At each time point, infants were assigned to either high or low IP ( Supplemental File 3 ).…”

Section: Resultssupporting

confidence: 60%

“…In this study, we studied a cohort of 38 preterm infants born prior to 33 weeks of gestation. IP was measured by urinary detection of orally administered sugar probes lactulose and rhamnose using high pressure liquid chromatography 16 with coinciding measures of the composition and function of the fecal microbial communities were investigated. We sampled three time points, study day 1, 8, and 15, during the first two weeks of life, which is a critical period corresponding to the initiation of the intestinal microbiota development process 16-18 .…”

Section: Introductionmentioning

confidence: 99%

“…IP was measured by urinary detection of orally administered sugar probes lactulose and rhamnose using high pressure liquid chromatography 16 with coinciding measures of the composition and function of the fecal microbial communities were investigated. We sampled three time points, study day 1, 8, and 15, during the first two weeks of life, which is a critical period corresponding to the initiation of the intestinal microbiota development process 16-18 . A rapid decrease in IP was observed to correlate with increased fecal microbiota biodiversity, indicating intestinal barrier function maturation over the first two weeks of life with a shift in the composition and structure in intestinal microbial community.…”

Section: Introductionmentioning

confidence: 99%

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Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants

McComb

Gajer

et al. 2018

Preprint

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19Intestinal barrier immaturity, or "leaky gut," is the proximate cause of susceptibility to 20 necrotizing enterocolitis in preterm neonates. However, the impact of intestinal 21 microbiota development on intestinal mucosal barrier maturation has not been 22 evaluated in this population. In this study, we investigated a longitudinally sampled 23 cohort of 38 preterm infants monitored for intestinal permeability (IP) and fecal 24 microbiota during the first two weeks of life. Rapid decrease in IP indicating intestinal 25 barrier function maturation correlated with significant increase in community diversity. In 26 particular, members of the Clostridiales and Bifidobacterium were highly 27 transcriptionally active, and progressively increasing abundance in Clostridiales was 28 significantly associated with decreased gut permeability. Further, neonatal factors 29 previously identified to promote intestinal barrier maturation, including early exclusive 30 breastmilk feeding and low antibiotic exposure, favor the early colonization of the gut 31 microbiota by members of the Clostridiales, which altogether are associated with 32 improved intestinal barrier function in preterm infants. 33 affecting approximately 7-10% of preterm neonates with mortality as high as 30-50% 13 . 57In this condition, bacteria across the intestinal wall leading to local and systemic 58 infection and inflammation, and bowel wall necrosis and perforation. Intestinal barrier 59 immaturity, characterized as elevated intestinal permeability (IP), or "leaky gut", is the 60 proximate cause of susceptibility to NEC in preterm neonates 14,15 . It is critical to 61 characterize the preterm infant intestinal microbiota to identify dysbiotic states 62 associated with increased intestinal leakiness, as well as beneficial bacteria associated 63 with improved intestinal barrier function, for subsequent stratification of early diagnosis, 64 early intervention and primary prevention of leaky gut and its sequelae. 65 66Despite the critical role of the microbial community in intestinal barrier function, its effect 67 on newborn IP is unknown. In particular, the microbiota of preterm neonates with 68 measured elevated IP, a high-risk population for NEC, has not been studied previously. 69We hypothesize that the intestinal microbiota plays a pivotal role in modulating IP and 70 that the presence of "beneficial" bacteria will be associated with improved intestinal 71 barrier function in preterm infants. In this study, we studied a cohort of 38 preterm 72 infants born prior to 33 weeks of gestation. IP was measured by urinary detection of 73 orally administered sugar probes lactulose and rhamnose using high pressure liquid 74 chromatography 16 with coinciding measures of the composition and function of the fecal 75 microbial communities were investigated. We sampled three time points, study day 1, 8, 76and 15, during the first two weeks of life, which is a critical period corresponding to the 77 initiation of the intestinal microbiota development process [16][17]...

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Section: Resultssupporting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants

McComb

Gajer

et al. 2018

Preprint

Self Cite

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“…Last, studies have begun to investigate the effects of microbiota on the BBB, the interface between the circulation and brain. Preterm infants have an underdeveloped intestinal barrier (Rouwet et al, ; Saleem et al, ), and gut dysbiosis has been associated with altered intestinal barrier function in the disease models (Claud, ; Hamilton, Boudry, Lemay, & Raybould, ). The BBB is the vascular endothelium that tightly governs the interaction between the circulatory system and CNS through regulation of transport which allows for proper neuronal function and also protects the CNS from toxins, pathogens, and inflammation (Daneman & Prat, ).…”

Section: Emerging Pathways Connecting Microbiome and Brain Developmentmentioning

confidence: 99%

Connection between gut microbiome and brain development in preterm infants

Lü

Claud

2018

Developmental Psychobiology

101

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Dysbiosis of the gut microbiome in preterm infants predisposes the neonate to various major morbidities including neonatal necrotizing enterocolitis and sepsis in the neonatal intensive care unit, and adverse neurological outcomes later in life. There are parallel early developmental windows for the gut microbiota and the nervous system during prenatal to postnatal of life. Therefore, preterm infants represent a unique population in which optimization of initial colonization and microbiota development can affect brain development and enhance neurological outcomes. In this review, we will first discuss the factors affecting the assembly of neonatal gut microbiota and the contribution of dysbiosis in preterm infants to neuroinflammation and neurodevelopmental disorders. We then will discuss the emerging pathways connecting the gut microbiome and brain development. Further we will discuss the significance of current models for alteration of the gut microbiome (including humanized gnotobiotic models and exposure to antibiotics) to brain development and functions. Understanding the role of early optimization of the microbiome in brain development is of paramount importance for developing microbiome‐targeted therapies and protecting infants from prematurity‐related neurodevelopmental diseases.

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“…A mixture of lactulose and rhamnose disaccharides is currently recommended for this test, but evaluation of urine samples is technically demanding [21]. Clinically more important is the fact that prematures suspected for NEC or newborns in septic shock are not allowed to consume any enteral substances, especially when it comes to just about research and not proved medication.…”

Section: Discussionmentioning

confidence: 99%

Zonulin: A Potential Marker of Intestine Injury in Newborns

et al. 2017

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Introduction Zonulin (ZO), a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. Material and Methods Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns). ZO concentration was compared to C-reactive protein (CRP) and procalcitonin (PCT) values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS). Results Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0–43.2) and 20.3 (1-3Q: 17.7–28.2) ng/ml, resp.) versus controls (3.5 (1-3Q: 2.7–4.8) ng/ml). Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. Conclusions Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

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

Cited by 52 publications

References 43 publications

Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants

Microbial Biomarkers of Intestinal Barrier Maturation in Preterm Infants

Connection between gut microbiome and brain development in preterm infants

Zonulin: A Potential Marker of Intestine Injury in Newborns

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