Hypoallergenic infant formula lacks transforming growth factor beta activity and has a lower anti-inflammatory activity than regular infant formula

Abstract

Hypoallergenic formulas are recommended for infants who are not breastfed and cannot tolerate cow milk formulas due to allergy. These formulas are hydrolyzed to break down larger protein chains into shorter, easy-to-digest, and potentially less allergenic proteins. Hydrolysis, however, possibly occurs at the expense of the transforming growth factor beta (TGF-β) and anti-inflammatory activity that is inherent in regular formula. Our objective was to determine the TGF-β and the anti-inflammatory activity of commercially available hypoallergenic and regular formulas. Human gingival fibroblasts were incubated with reconstituted formulas followed by detection of TGF-β target genes and activation of Smad2/3 signaling. Gingival fibroblasts and the oral squamous cell carcinoma cell line HSC-2 were also exposed to formulas before adding interleukin (IL)1β and tumor necrosis factor (TNF) α to provoke expression of pro-inflammatory cytokines. For murine bone marrow-derived macrophages, pro-inflammatory cytokine expression was stimulated with saliva. Changes in p65 nuclear translocation and phosphorylation of smad3 and p38 were analyzed by immunostaining. Our study demonstrated that regular formula, but not hypoallergenic formula, enhanced the expression of TGF-β target genes IL11, PRG4, and NOX4 in gingival fibroblasts. Hypoallergenic formulas also failed to initiate nuclear translocation of Smad2/3 and phosphorylation of Smad3. Moreover, regular formulas were more potent than hypoallergenic formulas in reducing the expression of pro-inflammatory cytokines in gingival fibroblasts, HSC-2 epithelial cells, and murine bone marrow macrophages. Hypoallergenic and regular formulas had a similar capacity to reduce p65 nuclear translocation and phosphorylation of p38 in fibroblasts. These findings suggest that hypoallergenic formulas lack in vitro TGF-β activity and have a lower anti-inflammatory activity compared with regular formulas.

Micellar Casein and Whey Powder Hold a TGF-β Activity and Regulate ID Genes In Vitro

“…Our data thus confirm the TGF-β activity of milk and dairy products including whey [11] and infant formula [12] based on the activation of TGF-β receptor I kinase expression of IL11 and NOX4 in oral fibroblasts, both genes that mediate the fibrotic activity of TGF-β in cardiovascular and liver fibrosis [8,9] and acute kidney injury and pulmonary fibrosis [10,30], respectively. PRG4 is involved in mediating TGF-β in osteoarthritis in mice [31].…”

“…The latter is an indirect evidence for the presence of lactoperoxidase, a heat stable milk enzyme, in casein and whey powder. We thus show that casein and whey maintain the basic in vitro properties of pasteurized milk we have recently reported [11,12,14].…”

“…In vitro, TGF-β activity is identified by its ability to regulate target genes, most notably interleukin11 (IL11), NADPH oxidase 4 (NOX4) and proteoglycan4 (PRG4) based on independent screening approaches [5][6][7], and some of TGF-β effects in vivo are mediated via IL11 [8,9] and NOX4 [10]. This in vitro bioassay was recently used to confirm that milk [11] but also regular infant formula has a potent TGF-β activity [12]. Nevertheless, casein and whey powder have not been tested for their TGF-β activity.…”

“…Thus, there is a demand to better understand the influence of casein and whey on oral cells. Considering that regular infant formula holds a potent TGF-β activity [12] that reduces allergic reactions in ovalbumin-tolerized mice [3], it is likely that this is also true for the main ingredient's casein and whey protein. If, however, casein and whey, similar to milk [14], activate cells of the epithelial cell lineage remains to be studied.…”

Aptamer-Based Fluorescent Biosensor for the Rapid and Sensitive Detection of Allergens in Food Matrices

“…Based on this, the aptamer assay with the range of 0.25-50 ng mL −1 and a LOD of 37 pg mL −1 has been successfully applied to the detection of trace β-lactoglobulin in HF. In the study of Qi et al, the binding mechanism of aptamer and β-lactoglobulin and the detection principle of fluorescent surface-enhanced Raman scattering (fluorescent-SERS) dual-mode aptamer sensor were thoroughly studied, which provides a theory basis and application potential for the development of aptamer sensors [166]. In Figure 4a, the circular dichroism of Lg-18, thermodynamic parameters analysis, secondary structure of Lg-18, and the result of molecular docking between aptamer Lg-18 and β-lactoglobulin were performed to illustrate the successful selection of aptamer.…”