Clostridia in Premature Neonates' Gut: Incidence, Antibiotic Susceptibility, and Perinatal Determinants Influencing Colonization

Although premature neonates (PN) gut microbiota has been studied, data about gut clostridial colonization in PN are scarce. Few studies have reported clostridia colonization in PN whereas Bacteroides and bifidobacteria have been seldom isolated. Such aberrant gut microbiota has been suggested to be a risk factor for the development of intestinal infections. Besides, PN are often treated by broad spectrum antibiotics, but little is known about how antibiotics can influence clostridial colonization based on their susceptibility patterns. The aim of this study was to report the distribution of Clostridium species isolated in feces from PN and to determine their antimicrobial susceptibility patterns. Additionally, clostridial colonization perinatal determinants were analyzed.Of the 76 PN followed until hospital discharge in three French neonatal intensive care units (NICUs), 79% were colonized by clostridia. Clostridium sp. colonization, with a high diversity of species, increased throughout the hospitalization. Antibiotic courses had no effect on the clostridial colonization incidence although strains were found susceptible (except C. difficile) to anti-anaerobe molecules tested. However, levels of colonization were decreased by either antenatal or neonatal (during more than 10 days) antibiotic courses (p = 0.006 and p = 0.001, respectively). Besides, incidence of colonization was depending on the NICU (p = 0.048).This study shows that clostridia are part of the PN gut microbiota. It provides for the first time information on the status of clostridia antimicrobial susceptibility in PN showing that strains were susceptible to most antibiotic molecules. Thus, the high prevalence of this genus is not linked to a high degree of resistance to antimicrobial agents or to the use of antibiotics in NICUs. The main perinatal determinant influencing PN clostridia colonization appears to be the NICU environment

Fecal Calprotectin Excretion in Preterm Infants during the Neonatal Period

Fecal calprotectin has been proposed as a non-invasive marker of intestinal inflammation in inflammatory bowel disease in adults and children. Fecal calprotectin levels have been reported to be much higher in both healthy full-term and preterm infants than in children and adults.To determine the time course of fecal calprotectin (f-calprotectin) excretion in preterm infants from birth until hospital discharge and to identify factors influencing f-calprotectin levels in the first weeks of life, including bacterial establishment in the gut.F-calprotectin was determined using an ELISA assay in 147 samples obtained prospectively from 47 preterm infants (gestational age, and birth-weight interquartiles 27–29 weeks, and 880–1320 g, respectively) at birth, and at 2-week intervals until hospital discharge. (p = 0.047).During the first weeks of life, the high f-calprotectin values observed in preterm infants could be linked to the gut bacterial establishment

Characterization of highly frequent epitope-specific CD45RA(+)/CCR7(+/- )T lymphocyte responses against p53-binding domains of the human polyomavirus BK large tumor antigen in HLA-A*0201+ BKV-seropositive donors

Human polyomavirus BK (BKV) has been implicated in oncogenic transformation. Its ability to replicate is determined by the binding of its large tumor antigen (LTag) to products of tumor-suppressor genes regulating cell cycle, as specifically p53. We investigated CD8+ T immune responses to BKV LTag portions involved in p53 binding in HLA-A*0201+ BKV LTag experienced individuals. Peptides selected from either p53-binding region (LTag(351–450 )and LTag(533–626)) by current algorithms and capacity to bind HLA-A*0201 molecule were used to stimulate CD8+ T responses, as assessed by IFN-γ gene expression ex vivo and detected by cytotoxicity assays following in vitro culture. We observed epitope-specific immune responses in all HLA-A*0201+ BKV LTag experienced individuals tested. At least one epitope, LTag(579–587); LLLIWFRPV, was naturally processed in non professional antigen presenting cells and induced cytotoxic responses with CTL precursor frequencies in the order of 1/20'000. Antigen specific CD8+ T cells were only detectable in the CD45RA+ subset, in both CCR7+ and CCR7- subpopulations. These data indicate that widespread cellular immune responses against epitopes within BKV LTag-p53 binding regions exist and question their roles in immunosurveillance against tumors possibly associated with BKV infection

Faecal Calprotectin in Term and Preterm Neonates: A Review

Objectives: This review aims to examine the characteristics of the faecal calprotectin assay in neonates and the evidence for its use as a noninvasive marker of intestinal illnesses during the neonatal period. Methods: Bibliographic searches were performed in MEDLINE electronic database up to February 2010 looking for the following words (all fields): (‘‘infants’’ or ‘‘neonates’’) and calprotectin. Twenty studies, in which 1180 neonates were enrolled, were selected. Results: During the neonatal period, calprotectin levels are characterized by significantly higher values in both healthy full-term and preterm infants during their first year of life compared with reference values established for children and adults. No difference was observed according to gestational age or birthweight, whereas a higher faecal calprotectin level was detected during intestinal distress in neonates with either inflammatory or patent digestive alterations. Despite high interindividual variations, cut-off levels are proposed to identify infants with high risk of intestinal illnesses. Conclusion: Compared with adults and children, healthy full-term and preterm neonates have high calprotectin levels. The measurement of calprotectin levels in faeces can be a promising noninvasive clinical screening test for intestinal distress in neonates

Fecal expression of human β-defensin-2 following birth.

Background: Newborns display high intestinal permeability and a naive adaptive immune system, but infections are rare, indicating strong innate defense mechanisms. Objective: To measure the kinetics of fecal -defensin-2 (HBD2), an induc- ible endogenous antimicrobial peptide produced by intesti- nal epithelial cells, in full-term and preterm infants. Meth- ods: As a first step of this bicentric study, we enrolled 30 healthy full-term infants and 20 healthy preterm infants, with fecal samples collected at days 3, 7 12 and 30 in full-term infants and at days 15, 30 and 60 in preterm infants. As a sec- ond step, we enrolled 10 preterm infants with intestinal dis- tress, either necrotizing enterocolitis (NEC) Bell’s stage III (n = 3) or isolated rectal bleeding (n = 7) and 20 controls, cross-matched for gestational age and age at sampling. Re- sults: HBD2 decreased significantly from day 3 to day 7 (227 ng/g; 14–440 vs. 117 ng/g; 30–470, p = 0.01) then moderate- ly until day 30 (84 ng/g; 10–500) in healthy full-term infants. Healthy preterm infants showed similar high levels between days 15 and 60 (82 ng/g; 30–154 and 85 ng/g; 26–390, respec- tively). No significant variation of fecal HBD2 levels was ob- served between infants with clinical features of intestinal distress (77 ng/g, 2–1,271) and cross-matched controls (56 ng/g, 31–164). However, 2/3 infants with NEC and 1/7 infants with isolated rectal bleeding had HBD2 levels above the maximal level observed in controls. Conclusions: The kinet- ics of fecal HBD2 in the neonatal period indicate that this inducible defensin can be detected at high level in the feces of full-term and preterm infants, independently of gesta- tional age or mode of feeding. The potential role of fecal HBD2 in detecting NEC is suggeste

Fecal calprotectin: cutoff values for identifying intestinal distress in preterm infants

ABSTRACT Objectives: This review aims to examine the characteristics of the faecal calprotectin assay in neonates and the evidence for its use as a noninvasive marker of intestinal illnesses during the neonatal period. Methods: Bibliographic searches were performed in MEDLINE electronic database up to February 2010 looking for the following words (all fields): (‘‘infants’’ or ‘‘neonates’’) and calprotectin. Twenty studies, in which 1180 neonates were enrolled, were selected. Results: During the neonatal period, calprotectin levels are characterized by significantly higher values in both healthy full-term and preterm infants during their first year of life compared with reference values established for children and adults. No difference was observed according to gestational age or birthweight, whereas a higher faecal calprotectin level was detected during intestinal distress in neonates with either inflammatory or patent digestive alterations. Despite high interindividual variations, cut-off levels are proposed to identify infants with high risk of intestinal illnesses. Conclusion: Compared with adults and children, healthy full-term and preterm neonates have high calprotectin levels. The measurement of calprotectin levels in faeces can be a promising noninvasive clinical screening test for intestinal distress in neonates

The role of the intestinal microbiota in the development of atopic disorders

The prevalence of atopic diseases, including eczema, allergic rhinoconjunctivitis and asthma, has increased worldwide, predominantly in westernized countries. Recent epidemiological studies and experimental research suggest that microbial stimulation of the immune system influences the development of tolerance to innocuous allergens. The gastrointestinal microbiota composition may be of particular interest, as it provides an early and major source of immune stimulation and seems to be a prerequisite for the development of oral tolerance. In this review the observational studies of the association between the gut microbiota and atopic diseases are discussed. Although most studies indicated an association between the gut microbiota composition and atopic sensitization or symptoms, no specific harmful or protective microbes can be identified yet. Some important methodological issues that have to be considered are the microbiological methods used (traditional culture vs molecular techniques), the timing of examining the gut microbiota, the definition of atopic outcomes, confounding and reverse causation. In conclusion, the microbiota hypothesis in atopic diseases is promising and deserves further attention. To gain more insight into the role of the gut microbiota in the etiology of atopy, large-scale prospective birth cohort studies using molecular methods to study the gut microbiota are needed