Role of the High Affinity Immunoglobulin E Receptor in Bacterial Translocation and Intestinal Inflammation

A role for immunoglobulin E and its high affinity receptor (FcεRI) in the control of bacterial pathogenicity and intestinal inflammation has been suggested, but relevant animal models are lacking. Here we compare transgenic mice expressing a humanized FcεRI (hFcεRI), with a cell distribution similar to that in humans, to FcεRI-deficient animals. In hFcεRI transgenic mice, levels of colonic interleukin 4 were higher, the composition of fecal flora was greatly modified, and bacterial translocation towards mesenteric lymph nodes was increased. In hFcεRI transgenic mice, 2,4,6-tri-nitrobenzenesulfonic acid (TNBS)-induced colitis was also more pronounced, whereas FcεRI-deficient animals were protected from colitis, demonstrating that FcεRI can affect the onset of intestinal inflammation

Comparison of two oral probiotic preparations in a randomized crossover trial highlights a potentially beneficial effect of Lactobacillus paracasei NCC2461 in patients with allergic rhinitis.

BACKGROUND: There is promising but conflicting evidence to recommend the addition of probiotics to foods for prevention and treatment of allergy. Based on previous studies with fermented milk containing Lactobacillus paracasei NCC2461, we aimed to compare the effect of a powder form of the latter probiotic with the effect of a blend of Lactobacillus acidophilus ATCC SD5221 and Bifidobacterium lactis ATCC SD5219 in patients with allergic rhinitis. METHODS: A double-blind, randomized, cross-over study, involving 31 adults with allergic rhinitis to grass pollen, was performed outside the grass pollen season (registration number: NCT01233154). Subjects received each product for 4-weeks in two phases separated by a wash-out period of 6 to 8 weeks. A nasal provocation test was performed before and after each 4-week product intake period, and outcome parameters (objective and subjective clinical symptoms; immune parameters) were measured during and/or 24 hours after the test. RESULTS: Out of the 31 subject enrolled, 28 completed the study. While no effect was observed on nasal congestion (primary outcome), treatment with NCC2461 significantly decreased nasal pruritus (determined by VAS), and leukocytes in nasal fluid samples, enhanced IL-5, IL-13 and IL-10 production by peripheral blood mononuclear cells in an allergen specific manner and tended to decrease IL-5 secretion in nasal fluid, in contrast to treatment with the blend of L. acidophilus and B. lactis. CONCLUSIONS: Despite short-term consumption, NCC2461 was able to reduce subjective nasal pruritus while not affecting nasal congestion in adults suffering from grass pollen allergic rhinitis. The associated decrease in nasal fluid leukocytes and IL-5 secretion, and the enhanced IL-10 secretion in an allergen specific manner may partly explain the decrease in nasal pruritus. However, somewhat unexpected systemic immune changes were also noted. These data support the study of NCC2461 consumption in a seasonal clinical trial to further demonstrate its potentially beneficial effect

Partially Hydrolysed Whey-Based Infant Formula Improves Skin Barrier Function

Specific partially hydrolysed whey-based infant formulas (pHF-W) have been shown to decrease the risk of atopic dermatitis (AD) in infants. Historically, AD has been associated primarily with milk allergy; however, defective skin barrier function can be a primary cause of AD. We aimed to ascertain whether oral supplementation with pHF-W can improve skin barrier function. The effect of pHF-W was assessed on transepidermal water loss (TEWL) and antibody productions in mice epicutaneously exposed to Aspergillus fumigatus. Human primary keratinocytes were stimulated in vitro, and the expression of genes related to skin barrier function was measured. Supplementation with pHF-W in neonatal mice led to a significant decrease in TEWL and total IgE, but not in allergen-specific antibody levels. The whey hydrolysate was sufficient to decrease both TEWL and total IgE. Aquaporin-3 gene expression, linked with skin hydration, was modulated in the skin of mice and human primary keratinocytes following protein hydrolysate exposure. Skin barrier improvement may be an additional mechanism by which pHF-W may potentially reduce the risk of AD development in infants. Further human studies are warranted to confirm the clinical efficacy of these observations

Identification of epicatechin as one of the key bioactive constituents of polyphenol-enriched extracts that demonstrate an anti-allergic effect in a murine model of food allergy

Polyphenols are naturally derived bioactive compounds with numerous reported health benefits. We have previously reported on the beneficial effect of a polyphenol-enriched apple extract in a murine model of food allergy. The objectives of the present study were to elucidate the class of bioactive polyphenols that exhibit a beneficial anti-allergic effect and to assess whether the protective effect matches the in vivo bioavailable metabolite concentrations. Female BALB/c mice were sensitised to ovalbumin (OVA) following the protocol of a well-established murine model of food allergy. They were fed diets containing polyphenol-enriched extracts or purified epicatechin for 8d after the last sensitisation. The sensitised mice were orally challenged with OVA after the intervention. The allergy symptoms, in addition to allergen-specific serum Ig concentrations and gene expression profiles in the intestine, of the control and treated mice were compared. Plasma samples were collected to compare the concentrations of bioavailable epicatechin metabolites in the treatment groups. Polyphenol-enriched fruit extracts containing epicatechin exhibited a significant anti-allergic effect in vivo. This effect was unambiguously attributed to epicatechin, as oral administration of this purified polyphenol to sensitised mice by inclusion in their diet modulated allergy symptoms in a dose-dependent manner. Immune parameters were also affected by the administration of epicatechin. Bioavailability measurements in plasma indicated that the attenuation of allergy symptoms could be due to the higher concentrations of bioavailable epicatechin metabolites. In conclusion, epicatechin is a key bioactive polyphenol that has the ability to modulate allergy outcomes in sensitised mic

Back to the Future: Studying Cholera Pathogenesis Using Infant Rabbits

Cholera is a severe diarrheal disease, caused by Vibrio cholerae, for which there has been no reproducible, nonsurgical animal model. Here, we report that orogastric inoculation of V. cholerae into 3-day-old rabbits pretreated with cimetidine led to lethal, watery diarrhea in virtually all rabbits. The appearance and chemical composition of the rabbit diarrheal fluid were comparable to those of the “rice-water stool” produced by cholera patients. As in humans, V. cholerae mutants that do not produce cholera toxin (CT) and toxin-coregulated pilus (TCP) did not induce cholera-like disease in rabbits. CT induced extensive exocytosis of mucin from intestinal goblet cells, and wild-type V. cholerae was predominantly found in close association with mucin. Large aggregates of mucin-embedded V. cholerae were observed, both attached to the epithelium and floating within the diarrheal fluid. These findings suggest that CT-dependent mucin secretion significantly influences V. cholerae’s association with the host intestine and its exit from the intestinal tract. Our model should facilitate identification and analyses of factors that may govern V. cholerae infection, survival, and transmission, such as mucin. In addition, our results using nontoxigenic V. cholerae suggest that infant rabbits will be useful for study of the reactogenicity of live attenuated-V. cholerae vaccines

Extensively hydrolysed infant formulas: Need for aligned definition of peptide size characteristics and standardisation of analytical methods

Letter by Nutten et al. on article by Levin et al. (Levin ME, Blackhurst DM, Kirstein F, Kok D, van der Watt GF, Marais AD. Residual allergenicity of amino acid-based and extensively hydrolysed cow’s milk formulas. S Afr Med J 2017;107(9):763-767. S Afr Med J 2017;107(3):258-263. https://doi.org/10.7196/SAMJ.2017.v107i9.12137); and response by Levin et al

Attenuation of Colon Inflammation through Activators of the Retinoid X Receptor (Rxr)/Peroxisome Proliferator–Activated Receptor γ (Pparγ) Heterodimer: A Basis for New Therapeutic Strategies

The peroxisome proliferator–activated receptor γ (PPARγ) is highly expressed in the colon mucosa and its activation has been reported to protect against colitis. We studied the involvement of PPARγ and its heterodimeric partner, the retinoid X receptor (RXR) in intestinal inflammatory responses. PPARγ1/− and RXRα1/− mice both displayed a significantly enhanced susceptibility to 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis compared with their wild-type littermates. A role for the RXR/PPARγ heterodimer in the protection against colon inflammation was explored by the use of selective RXR and PPARγ agonists. TNBS-induced colitis was significantly reduced by the administration of both PPARγ and RXR agonists. This beneficial effect was reflected by increased survival rates, an improvement of macroscopic and histologic scores, a decrease in tumor necrosis factor α and interleukin 1β mRNA levels, a diminished myeloperoxidase concentration, and reduction of nuclear factor κB DNA binding activity, c-Jun NH2-terminal kinase, and p38 activities in the colon. When coadministered, a significant synergistic effect of PPARγ and RXR ligands was observed. In combination, these data demonstrate that activation of the RXR/PPARγ heterodimer protects against colon inflammation and suggest that combination therapy with both RXR and PPARγ ligands might hold promise in the clinic due to their synergistic effects