Early infancy dysbiosis in food protein-induced enterocolitis syndrome: A prospective cohort study.

BACKGROUND: The microbiome associations of food protein-induced enterocolitis syndrome (FPIES) are understudied. We sought to prospectively define the clinical features of FPIES in a birth cohort, and investigate for the evidence of gut dysbiosis. METHODS: We identified children diagnosed with FPIES in the Gastrointestinal Microbiome and Allergic Proctocolitis Study, a healthy infant cohort. Children were assessed and stools were collected at each well child visit. The clinical features of the children with FPIES were summarized. Stool microbiome was analyzed using 16S rRNA sequencing comparing children with and without FPIES. RESULTS: Of the 874 children followed up for 3 years, 8 FPIES cases (4 male) were identified, yielding a cumulative incidence of 0.92%. The most common triggers were oat and rice (n = 3, each) followed by milk (n = 2). The children with FPIES were more likely to have family history of food allergy (50% vs. 15.9% among unaffected, p = .03). The average age of disease presentation was 6 months old. During the first 6 months of life, stool from children with FPIES contained significantly less Bifidobacterium adolescentis, but more pathobionts, including Bacteroides spp. (especially Bacteroides fragilis), Holdemania spp., Lachnobacterium spp., and Acinetobacter lwoffii. The short-chain fatty acid (SCFA)-producing Bifidobacterium shunt was expressed significantly less in the stool from FPIES children. CONCLUSIONS: In this cohort, the cumulative incidence over the 3-year study period was 0.92%. During the first 6 months of life, children with FPIES had evidence of dysbiosis and SCFA production pathway was expressed less in their stool, which may play an important role in the pathogenesis of FPIES.

Prospective Assessment of Pediatrician-Diagnosed Food Protein-Induced Allergic Proctocolitis by Gross or Occult Blood.

BACKGROUND: Food protein-induced allergic proctocolitis (FPIAP) is an early and common manifestation of food allergy, yet its epidemiology and relationship to other allergic diseases remain unclear. OBJECTIVE: To prospectively define the incidence of FPIAP as it is being diagnosed clinically in the community and to identify factors associated with its development. METHODS: A total of 1003 of 1162 eligible serial healthy newborn infants recruited from a single suburban pediatrics practice were followed prospectively for the diagnosis of FPIAP. Investigators reviewed each case to confirm prespecified inclusion criteria, including documented gross or occult blood in the stool. RESULTS: A total of 903 infants were analyzed (46% females, 89% term, 32% caesarian-section, 9% neonatal antibiotics); 153 cases met inclusion criteria, a cumulative incidence of 17%, while 63 (7%) had gross blood. Infants initially fed both breast milk and formula were 61% less likely to develop FPIAP compared with those exclusively formula-fed (hazard ratio, 0.39; P = .005). Breast milk and formula at any point during the first 4 months were also associated with lower risk compared with exclusive formula or exclusive breast milk (hazard ratio, 0.44; P = .005; hazard ratio, 0.62; P = .0497). Eczema (odds ratio, 1.5; 95% confidence interval, 1.1- 2.2; P = .02) or a first-degree relative with food allergies (odds ratio, 1.9; 95% confidence interval, 1.2-2.8; P = .005) were among risk factors for FPIAP development. CONCLUSIONS: The prospectively defined incidence of FPIAP when diagnosed clinically by community pediatricians without challenge is markedly higher than published estimates. Combination feeding of formula and breast milk is associated with the lowest rate of FPIAP in this population.

The Bioavailability of Soluble Cigarette Smoke Extract Is Reduced through Interactions with Cells and Affects the Cellular Response to CSE Exposure.

Cellular exposure to cigarette smoke leads to an array of complex responses including apoptosis, cellular senescence, telomere dysfunction, cellular aging, and neoplastic transformation. To study the cellular response to cigarette smoke, a common in vitro model exposes cultured cells to a nominal concentration (i.e. initial concentration) of soluble cigarette smoke extract (CSE). However, we report that use of the nominal concentration of CSE as the only measure of cellular exposure is inadequate. Instead, we demonstrate that cellular response to CSE exposure is dependent not only on the nominal concentration of CSE, but also on specific experimental variables, including the total cell number, and the volume of CSE solution used. As found in other similar xenobiotic assays, our work suggests that the effective dose of CSE is more accurately related to the amount of bioavailable chemicals per cell. In particular, interactions of CSE components both with cells and other physical factors limit CSE bioavailability, as demonstrated by a quantifiably reduced cellular response to CSE that is first modified by such interactions. This has broad implications for the nature of cellular response to CSE exposure, and for the design of in vitro assays using CSE.