Noninvasive measurement of intestinal epithelial damage at time of refeeding can predict clinical outcome after necrotizing enterocolitis

Reisinger, Kostan W.; Derikx, Joep P. M.; Thuijls, Geertje; Zee, David C. van der; Brouwers, H. A. A.; Bijnen, Annemarie A. van; Wolfs, Tim G. A. M.; Heurn, L. W. Ernest van; Buurman, Wim A.; Kramer, Boris W.

doi:10.1038/pr.2012.160

Cited by 30 publications

(17 citation statements)

References 25 publications

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“…This seems however unlikely as the current data do not show differences between GA groups in mucosal proliferation rates in the first days after birth. Second, the stimuli of bacterial colonization after birth may lead to an inflammatory response, leading to damage of immature enterocytes due to inadequate In a recent study, we have shown that differences in urinary I-FABP levels are not affected when corrected for creatinine even in severely ill neonates (24). The data in this study have important implications.…”

Section: Discussionmentioning

confidence: 45%

Intestinal fatty acid–binding protein: a possible marker for gut maturation

et al. 2014

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Background: Gut immaturity is linked with postnatal intestinal disorders. However, biomarkers to assess the intestinal developmental stage around birth are lacking. The aim of this study was to gain more insight on intestinal fatty acid-binding protein (I-FABP) as an indicator of gut maturity. Methods: Antenatal I-FABP distribution and release was investigated in extremely premature, moderately premature, and term lambs, and these findings were verified in human urinary samples. Ileal I-FABP distribution was confirmed in autopsy material within 24 h postnatally. results: Median (range) serum I-FABP levels were lower in extremely premature lambs compared with moderately premature lambs (156 (50.0-427) vs. 385 (100-1,387) pg/ml; P = 0.02). Contrarily, median early postnatal urine I-FABP levels in human infants were higher in extremely premature compared with moderately premature and term neonates (1,219 (203-15,044) vs. 256 (50-1,453) and 328 (96-1,749) pg/ml; P = 0.008 and P = 0.04, respectively). I-FABP expression was most prominent in nonvacuolated enterocytes and increased with rising gestational age (GA) in ovine and human tissue samples. The epithelial distribution pattern changed from a phenotype displaying I-FABP-positive enterocytes merely in the crypts early in gestation into a phenotype with I-FABP expressing cells exclusively present in the villus tips at term in ovine and human tissue. conclusion: In this ovine and human study, increasing GA is accompanied by an increase in I-FABP tissue content. Cord I-FABP levels correlate with gestation in ovine fetuses, identifying I-FABP as a marker for gut maturation. Raised postnatal urine I-FABP levels in preterm human infants may indicate intestinal injury and/or inflammation in utero.

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Section: Discussionmentioning

confidence: 45%

Intestinal fatty acid–binding protein: a possible marker for gut maturation

et al. 2014

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“…While our finding of improved enterocyte integrity with any early EN supports the role of early EN in gut protection, it may be that children who cannot be fed have a priori worse intestinal epithelial barrier function. Previous studies have shown that for infants with necrotizing enterocolitis (NEC), elevated plasma FABP2 concentrations after resumption of EN is a marker of poor outcome 26 , suggesting that biomarkers of intestinal epithelial barrier function could reflect readiness for EN. These biomarkers require further study as possible targets for EN readiness and tolerance.…”

Section: Resultsmentioning

confidence: 99%

Clinical Characteristics Associated With Postoperative Intestinal Epithelial Barrier Dysfunction in Children With Congenital Heart Disease*

Typpo

Larmonier

Deschenes

et al. 2015

Pediatric Critical Care Medicine

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Objective Children with congenital heart disease (CHD) have loss of intestinal epithelial barrier function (EBF), which increases their risk for post-operative sepsis and organ dysfunction. We do not understand how post-operative cardiopulmonary support or the inflammatory response to cardiopulmonary bypass (CPB) might alter intestinal EBF. We examined variation in a panel of plasma biomarkers to reflect intestinal EBF (cellular and paracellular structure and function) after CPB and in response to routine ICU care. Design Prospective cohort Setting University medical center cardiac intensive care unit Patients Twenty children aged newborn to 18 years undergoing repair or palliation of CHD with CPB. Interventions We measured baseline and repeated plasma FABP2, citrulline, claudin 3, and dual sugar permeability test (DSPT) to reflect intestinal epithelial integrity, epithelial function, paracellular integrity, and paracellular function, respectively. We measured baseline and repeated plasma pro-inflammatory (IL-6, TNF-α, IFN-γ) and anti-inflammatory (IL4, IL10) cytokines, known to modulate intestinal EBF in murine models of CPB. Measurements and Main Results All patients had abnormal baseline FABP2 concentrations (mean 3815.5 pg/mL), (normal 41–336 pg/mL). Cytokine response to CPB was associated with early, but not late changes in plasma concentrations of FABP2 and citrulline. Variation in biomarker concentrations over time were associated with aspects of ICU care indicating greater severity of illness: claudin 3, FABP2, and DSPT ratio were associated with symptoms of feeding intolerance (p<0.05) while FABP2 was positively associated with vasoactive-inotrope score (VIS) (p=0.04). Citrulline was associated with larger arteriovenous O2 saturation difference (p=0.04) and had a complex relationship with VIS. Conclusions Children undergoing CPB for repair or palliation of CHD are at risk for intestinal injury and often present with evidence for loss of intestinal epithelial integrity pre-operatively. Greater severity of illness requiring increased cardiopulmonary support rather than the inflammatory response to CPB seems to mediate late post-operative intestinal EBF.

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“…All protein markers can be measured in plasma and urine using ELISA. To date they have been used only in clinical studies; for example, in patients with celiac disease, intestinal ischemia, necrotizing colitis (3, 211, 212, 253, 273), and in patients who have undergone liver transplant in which their prognostic value was demonstrated (182). Alternative small-molecule markers of intestinal epithelial integrity include TJ proteins.…”

Section: Biomarkers Of Intestinal Epithelial Permeability and Integrimentioning

confidence: 99%

Homeostasis of the gut barrier and potential biomarkers

Wells

Brummer

Derrien

et al. 2017

American Journal of Physiology-Gastrointestinal and Liver Physi

478

377

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The gut barrier plays a crucial role by spatially compartmentalizing bacteria to the lumen through the production of secreted mucus and is fortified by the production of secretory IgA (sIgA) and antimicrobial peptides and proteins. With the exception of sIgA, expression of these protective barrier factors is largely controlled by innate immune recognition of microbial molecular ligands. Several specialized adaptations and checkpoints are operating in the mucosa to scale the immune response according to the threat and prevent overreaction to the trillions of symbionts inhabiting the human intestine. A healthy microbiota plays a key role influencing epithelial barrier functions through the production of short-chain fatty acids (SCFAs) and interactions with innate pattern recognition receptors in the mucosa, driving the steady-state expression of mucus and antimicrobial factors. However, perturbation of gut barrier homeostasis can lead to increased inflammatory signaling, increased epithelial permeability, and dysbiosis of the microbiota, which are recognized to play a role in the pathophysiology of a variety of gastrointestinal disorders. Additionally, gut-brain signaling may be affected by prolonged mucosal immune activation, leading to increased afferent sensory signaling and abdominal symptoms. In turn, neuronal mechanisms can affect the intestinal barrier partly by activation of the hypothalamus-pituitary-adrenal axis and both mast cell-dependent and mast cell-independent mechanisms. The modulation of gut barrier function through nutritional interventions, including strategies to manipulate the microbiota, is considered a relevant target for novel therapeutic and preventive treatments against a range of diseases. Several biomarkers have been used to measure gut permeability and loss of barrier integrity in intestinal diseases, but there remains a need to explore their use in assessing the effect of nutritional factors on gut barrier function. Future studies should aim to establish normal ranges of available biomarkers and their predictive value for gut health in human cohorts.

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Noninvasive measurement of intestinal epithelial damage at time of refeeding can predict clinical outcome after necrotizing enterocolitis

Cited by 30 publications

References 25 publications

Intestinal fatty acid–binding protein: a possible marker for gut maturation

Intestinal fatty acid–binding protein: a possible marker for gut maturation

Clinical Characteristics Associated With Postoperative Intestinal Epithelial Barrier Dysfunction in Children With Congenital Heart Disease*

Homeostasis of the gut barrier and potential biomarkers

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