Birth gestational age seems to act as a major determinant of bifidobacterial colonization in the premature infant, suggesting the role of gut maturation, a finding that should probably be taken into account in manipulations of the gut flora aimed at reducing NEC.

Background: Calprotectin, a major component of soluble cytosolic proteins in human neutrophil granulocytes, is excreted in excess in stools during inflammatory bowel disease in adults and children. Faecal calprotectin concentrations are also higher during the first year of life than in adults. Objectives: To measure faecal calprotectin concentrations in the neonatal period and define reference values according to the mode of feeding: standard infant formula, prebiotic infant formula (Calisma, Blédina SA, France), or breast feeding. Patients and methods: A prospective study was carried out over three months in 69 full term, healthy newborns with a median gestational age of 39.8 weeks (range 37-41.5) and a birth weight of 3300 g (range 2600-4460). Three groups were formed depending on the mode of feeding: group 1 (n = 18) received a standard infant formula, group 2 (n = 19) the prebiotic infant formula, and group 3 (n = 32) was breast fed. One stool sample was taken from each newborn on day 4 (3-7), and faecal calprotectin analysed using a commercial enzyme linked immunoassay (Calprest, Eurospital, Italy). Results: Faecal calprotectin concentrations (median 167 mg/g) were higher than reference values in healthy adults. The concentration was below the upper reference limit for adults (50 mg/g) for three infants only, one fed the standard formula and two fed the prebiotic formula. Concentrations did not differ significantly according to method of feeding. Conclusions: Compared with healthy adults, newborns have high calprotectin concentrations in the first days of life. There is no obvious influence of the mode of feeding.

Congenital tufting enteropathy (CTE) is a rare and severe enteropathy recently ascribed to mutations in the epcam gene. Here we establish SPINT2, previously ascribed to congenital sodium diarrhea, as a second gene associated with CTE and report molecular and immunohistochemistry data in 57 CTE patients. Inclusion criteria were early onset diarrhea and intestinal insufficiency with the typical histological CTE abnormalities. The clinical phenotype was registered, the entire coding regions of epcam and SPINT2 sequenced, and immunostaining of EpCAM and SPINT2 performed on intestinal biopsies. An epcam mutation was involved in 41 patients (73 %) who mainly displayed isolated digestive symptoms. Mutations severely affected gene expression since the EpCAM signal on intestinal tissues was either undetectable or low and irregular. Twelve other patients (21 %) carried mutations in SPINT2, and were phenotypically characterized by systematic association with keratitis (p < 10(-4)) and, for half of them, with choanal atresia (p < 10(-4)). Dependency on parenteral nutrition (PN) was comparable in patients with epcam or SPINT2 mutations, but the frequent epcam mutation c.556-14A>G (abnormal splicing) was significantly associated with a better outcome (p = 0.032) with milder PN dependency to weaning in some cases. Finally, four patients (7 %) with isolated digestive symptoms had no detectable epcam or SPINT2 mutation. Two candidate genes, Elf3 and Claudin7, were excluded from this population. Our study allows us to separate CTE patients into at least three genetic classes, each with specific phenotypes. The genetics approach raises the question of the distinction between two congenital enteropathies. Our findings should help improve the diagnosis of CTE, guide toward strategies of long-term PN management, and limit indications for intestinal transplantation to life-threatening PN complications.