Decreased allergy incidence in children supplemented with E. coli O83:K24:H31 and its possible modes of action

Abstract

The growing knowledge of the key role of microbiota in the maturation of neonatal immune system suggests that manipulation of microbiota could be exploited in hampering allergy development. In this study, Escherichia coli O83:K24:H31 (EcO83) was administered to newborns that were followed prospectively. Several immunological characteristics (cytokines, specific IgE, total T regulatory cells (Treg) and subpopulation of natural Treg (nTreg) and induced Treg (iTreg)) were tested in peripheral blood of 8-year-old children. Incidence of allergic disease was decreased in EcO83 supplemented children and significantly elevated levels of IL-10 and IFN-ɣ were detected in serum of EcO83 supplemented children. Probiotic supplementation did not influence the numbers of the total Treg population but their functional capacity (intracellular expression of IL-10) was significantly increased in children supplemented with EcO83 in comparison to nonsupplemented children. Morover, decreased proportion of iTreg was present in peripheral blood of non-supplemented in comparison to EcO83 supplemented children. Finally, stimulation of cord blood cells with EcO83 promoted both gene expression and secretion of IL-10 and IFN-ɣ suggesting that beneficial effect of EcO83 in prevention of allergy development could be mediated by promotion of regulatory responses (by IL-10) and Th1 immune response (by IFN-ɣ). Keywords: allergy r cord blood r E. coli r probiotics r Treg Additional supporting information may be found online in the Supporting Information section at the end of the article. , L. et al., Guidelines for the use of flow cytometry and cell sorting in immunological studies. Eur. J. Immunol. 2017. 47: 1584-1797. Abbreviations: CBMC: cord blood mononuclear cells · CFU: colony forming units · EcO83: Escherichia coli O83:K24:H31 · IQR: interquartile range · nTreg: natural Treg · Treg: T regulatory cells · iTreg: induced Treg

Value of cord blood Treg population properties and function-associated characteristics for predicting allergy development in childhood

“…Several studies have correlated population characteristics and functional properties of Tregs with atopic diseases in small infants [16,[24][25][26][27]. In our own work published by Hrdý in 2012 [17], we reported lower presence of intracellular markers associated with Treg function (IL-10, TGF-β, MFI of FoxP3) in Tregs from cord blood of children at higher risk of allergy development (based on maternal allergy status).…”

“…presence of surface or intracellular markers, median of fluorescence intensity [MFI] of FoxP3 [14]) and systemically (e.g. levels of regulatory cytokines in serum measured by ELISA [15,16]).…”

“…Despite marked progress in understanding the early processes involved in sensitization and allergy development, there is still lack of definite consensus regarding reliable early predictors of an individual's increased risk of allergy. Numerous markers have been analysed in cord blood, including cord blood IgE levels [18], levels of cytokines including IL-10 and TGF-β in cord blood [15] and neonatal peripheral blood [19] plasma, as well as reactivity of cord blood cells to various stimuli, with limited conclusiveness when taken together [16,[20][21][22][23]. So far, the allergy status of the mother remains the strongest unambiguously accepted predictive factor [23].…”

Microbiota Signals during the Neonatal Period Forge Life-Long Immune Responses

“…This treatment also diminishes NF-κB cascade function and IL-8 levels, while increasing IL-10 concentration in the colon [ 168 ]. Neonatal therapy with E. coli O83:K24:H31 reduces allergy rates, augments T regulatory cells and elevates their IL-10 expression, as well as raising serum IL-10 and IFN-γ levels in children [ 169 ]. Treatment with Bifidobacterium bifidum TMC3115 during the neonatal period augments fecal bacterial variety, caecal SCFAs generation and Bacteroidetes prevalence.…”

Lower Functional and Proportional Characteristics of Cord Blood Treg of Male Newborns Compared with Female Newborns

“…Nevertheless, despite the progress in our understanding of the early etiopathology of allergy development, few reliable predictors of individual risk have been conclusively identified so far. Various factors have been studied without much success, including cord blood IgE [29,30], levels of IL-10, TGF-β and/or Th1-and Th2-related cytokines in cord blood [31,32] and neonatal peripheral blood plasma [33], as well as the reactivity of cord blood-derived cells to diverse stimuli under various conditions [34][35][36][37][38]. So far, parental allergy status, especially maternal or biparental allergy, seems to be the most reliable predictor of risk for allergy development at an individual level [38,39].…”