New Concepts of Microbial Translocation in the Neonatal Intestine: Mechanisms and Prevention
Section snippets
General Principles
Healthy term infants stay with their mothers, breastfeed, and acquire intestinal microflora from the mother that is genetically compatible. This theory, espoused by Hooper and colleagues,8 holds that proper postnatal acquisition of genetically compatible gut microbiota improves nutrition and fortifies the gut's epithelial barrier. In contrast, VLBW infants are almost always separated from their mothers and are cared for in a neonatal ICU containing resistant and invasive pathogens. Although
Gut epithelia and protection against bacterial translocation
The mechanisms used by goblet cells, enterocytes, and Paneth cells to protect VLBW infants from BT are summarized in Table 1.46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66
General Principles
During the third trimester of pregnancy, the fetus swallows nutrient-, growth factor-, and antibiotic peptide–rich amniotic fluid.69 Human milk is even more complex than amniotic fluid, and it continues to enhance intestinal development after birth.70 In addition to its nutrient composition, human milk contains hormones, growth factors, cytokines, immunomodulators, natural peptide antibiotics, sIgA, and probiotic bacteria.70, 71, 72, 73, 74, 75, 76 sIgA in milk is the end result of crosstalk
Summary
Bacterial translocation from the GI tract is an important pathway initiating late-onset sepsis and necrotizing enterocolitis in very low-birth-weight infants. The emerging intestinal microbiota, nascent intestinal epithelia, naive immunity, and suboptimal nutrition (lack of breast milk) have roles in facilitating bacterial translocation. Feeding lactoferrin, probiotics, or prebiotics has presented exciting possibilities to prevent bacterial translocation in preterm infants, and clinical trials
References (114)
- et al.
Neonatal gut barrier and multiple organ failure: role of endotoxins and proinflammatory cytokines in sepsis and necrotizing enterocolitis
J Pediatr Surg
(2007) Symposium: bioactivity in milk and bacterial interactions in the developing immature intestine
J Nutr
(2000)- et al.
The intestinal bacterial colonization in preterm infants: a review of the literature
Clin Nutr
(2006) - et al.
Nosocomial colonization with Klebsiella, type 26, in a neonatal intensive-care unit associated with an outbreak of sepsis, meningitis, and necrotizing enterocolitis
J Pediatr
(1974) - et al.
Intestinal microbial ecology in premature infants assessed with non-culture-based techniques
J Pediatr
(2010) - et al.
Pathologic and physiologic interactions of bacteria with the gastrointestinal epithelium
Am J Clin Nutr
(2001) - et al.
The dyspeptic macrophage 30 years later: an update in the pathogenesis of Crohn's disease
Dig Liver Dis
(2009) - et al.
The role of enterocytes in the intestinal barrier function and antigen uptake
Microbes Infect
(2005) - et al.
Paneth cells, defensins, and the commensal microbiota: a hypothesis on intimate interplay at the intestinal mucosa
Semin Immunol
(2007) - et al.
Necrotizing enterocolitis of the neonate
Clin Perinatol
(1989)
Human enteric defensins. Gene structure and developmental expression
J Biol Chem
Prenatal and postnatal corticosteroid therapy to prevent neonatal necrotizing enterocolitis, a controlled trial
J Pediatr
Human milk is a source of lactic acid bacteria for the infant gut
J Pediatr
Novel lactoferrampin antimicrobial peptides derived from human lactoferrin
Biochimie
Effect of lactoferrin on enteric pathogens
Biochimie
Growth promotion and cell binding ability of bovine lactoferrin to Bifidobacterium longum
Anaerobe
Alarmins link neutrophils and dendritic cells
Trends Immunol
The probiotic century: historical and current perspectives
Trends Food Sci Technol
Prebiotics in human milk: a review
Dig Liver Dis
Probiotic bacterium prevents cytokine-induced apoptosis in intestinal epithelial cells
J Biol Chem
Late-onset sepsis in very low birth weight neonates: the experience of the NICHD Neonatal Research Network
Pediatrics
Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection
JAMA
Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in gnotobiotic mouse model
Infect Immun
Review article: bacterial translocation in the critically ill—evidence and methods of prevention
Aliment Pharmacol Ther
Understanding the susceptibility of the premature infant to necrotizing enterocolitis (NEC)
Pediatr Res
Molecular analysis of commensal host-microbial relationships in the intestine
Science
Late-onset septicemia in a Norwegian national cohort of extremely premature infants receiving early full human milk feeding
Pediatrics
Reduced enterobacterial and increased staphylococcal colonization of the infantile bowel: an effect of hygienic lifestyle?
Pediatr Res
A roadmap for understanding and preventing necrotizing enterocolitis
Curr Gastroenterol Rep
Intestinal flora in very-low birth weight infants
Acta Paediatr
Delta-like toxin produced by coagulase-negative staphylococci is associated with neonatal necrotizing enterocolitis
Infect Immun
Neonatal necrotizing enterocolitis associated with delta-toxin producing methicillin-resistant Staphylococcus aureus
Pediatr Infect Dis J
Gastrointestinal microbiology enters the metagenomics era
Curr Opin Gastroenterol
Tools for stools: the challenge of assessing human intestinal microbiota using molecular diagnostics
Expert Rev Mol Diagn
Redefining the role of intestinal microbes in the pathogenesis of necrotizing enterocolitis
Pediatrics
Early intestinal bacterial colonization and necrotizing enterocolitis in premature infants: the putative role of Clostridium
Pediatr Res
16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis
ISME J
Role of gut microbiota in Crohn's disease
Expert Rev Gastroenterol Hepatol
Shigellosis: innate mechanisms of inflammatory destruction of intestinal epithelium, adaptive immune response, and vaccine development
Crit Rev Immunol
The human microbiome project
Nature
Transcytosis of gastrointestinal epithelial cells by Escherichia coli K1
Pediatr Res
Structural microbiology at the pathogen–host interface
Cell Microbiol
Bacterial invasion: the paradigms of enteroinvasive pathogens
Science
Invasion of epithelial cells by locus of enterocytes effacement-negative enterohemorrhagic Escherichia coli
Infect Immun
Role of EHEC O157:H7 virulence factors in the activation of intestinal epithelial cell NF-kB and MAP kinase pathways and the upregulated expression of interleukin 8
Cell Immunol
Enteropathogenic Escherichia coli (EPEC) inactivate innate immune responses prior to compromising epithelial barrier function
Cell Immunol
The role of the intestinal barrier in the pathogenesis of necrotizing enterocolitis
Shock
Enterobacter sakazakii invasion in human intestinal Caco-2 cells requires the host cell cytoskeleton and is enhanced by disruption of tight junctions
Infect Immun
Epidemiology of invasive neonatal Cronobacter (Enterobacter sakazakii) infections
Eur J Clin Microbiol Infect Dis
Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier
J Immunol
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Link between gut microbiota and neonatal sepsis
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2022, Clinical TherapeuticsCitation Excerpt :Lactoferrin (LF), the second most abundant protein in breast milk,61 is a multifunctional bioactive glycoprotein. It is known to have antimicrobial, anti-inflammatory, immunomodulatory, and growth-promoting properties that may prevent bacterial translocation in the intestines of premature neonates.62 Higher concentrations of LF are found in colostrum and in milk from mothers who deliver preterm.63
Does probiotic bacteremia in premature infants impact clinically relevant outcomes? A case report and updated review of literature
2020, Clinical Nutrition ESPENCitation Excerpt :Intestinal permeability in preterm infants is crucial to maintain the delicate balance between absorption of nutrients and protection from pathogens [26]. Bacterial translocation from the intestinal tract is an important pathway initiating late-onset sepsis and necrotizing enterocolitis in VLBW infants [27]. Preterm infants are frequently exposed to antibiotics, which decreases gut microbial diversity and promotes a pathogen-predominant microbiota that is associated with sepsis [28].
Antecedents of Objectively Diagnosed Diffuse White Matter Abnormality in Very Preterm Infants
2020, Pediatric NeurologyAssessment of bioactivities of the human milk lactoferrin–osteopontin complex in vitro
2019, Journal of Nutritional Biochemistry
This research was supported by NIH grant R44 HD057744 and a Gerber Foundation grant.