Childhood allergy susceptibility: The role of the immune system development in the in-utero period

Zainal, Nurul Hayati Mohamad; Nor, Nurul Huda Mohd; Saat, Azmah; Clifton, Vicki L.

doi:10.1016/j.humimm.2022.02.002

Cited by 6 publications

(3 citation statements)

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“…Children attending daycare are exposed to similar cross‐infection and have also been reported to have a lower risk of allergic rhinitis, 57–59 further indicating that microbial environment during early childhood influences immune development and subsequent risk of allergic diseases. It is also possible, however, that other types of exposures, behaviors, or even immunological in utero interactions associated with specific birth order positions may contribute or be the driving factor(s), 60,61 and to this date, none of the investigated underlying mechanistic factors have emerged as a robust explanation for the effect of sibship composition 62 …”

Section: Discussionmentioning

confidence: 99%

“…It is also possible, however, that other types of exposures, behaviors, or even immunological in utero interactions associated with specific birth order positions may contribute or be the driving factor(s), 60,61 and to this date, none of the investigated underlying mechanistic factors have emerged as a robust explanation for the effect of sibship composition. 62 The weaker association of birth order and sibship size with allergic rhinoconjunctivitis may be because of increased recall bias and misinterpretation, given the more specified symptom definition.…”

Section: Interpretation Of Findingsmentioning

confidence: 99%

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Siblings and risk of allergic rhinitis: A systematic review and meta‐analysis

Lisik

Ermis

Ioannidou

et al. 2023

Pediatric Allergy Immunology

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Following the “hygiene hypothesis” and the increase in the prevalence of atopic diseases such as allergic rhinitis, a plethora of studies have investigated the role of sibship composition as a protective factor, but findings are conflicting. The aim of this study was to synthesize the global literature linking birth order and sibship size (number of siblings) to the risk of allergic rhinitis. Fifteen databases were systematically searched, with no restrictions on publication date or language. Observational studies with defined sibship composition (birth order or sibship size) as exposure and allergic rhinitis or allergic rhinoconjunctivitis (self‐reported or clinically diagnosed) as outcome were eligible. Study selection, data extraction, and quality assessment were performed independently in pairs. Relevant data were summarized in tables. Comparable numerical data were analyzed using meta‐analysis with robust variance estimation (RVE). Seventy‐six reports with >2 million subjects were identified. Being second‐ or later‐born child was associated with protection against both current (pooled risk ratio [RR] 0.79, 95% CI 0.73–0.86) and ever (RR 0.77, 95% CI 0.68–0.88) allergic rhinitis. Having siblings, regardless of birth order, was associated with a decreased risk of current allergic rhinitis (RR 0.89, 95% CI 0.83–0.95) and allergic rhinoconjunctivitis (RR 0.92, 95% CI 0.86–0.98). These effects were unchanged across age, time period, and geographical regions. Our findings thus indicate that primarily, a higher birth order, and to a lesser extent the number of siblings, is associated with a lower risk of developing allergic rhinitis.

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Section: Discussionmentioning

confidence: 99%

Section: Interpretation Of Findingsmentioning

confidence: 99%

Siblings and risk of allergic rhinitis: A systematic review and meta‐analysis

Lisik

Ermis

Ioannidou

et al. 2023

Pediatric Allergy Immunology

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“…Early life has been identified as a window of opportunity for preventing food allergic diseases. During the first 1,000 days of life, the immune system matures and moves away from the pre- and neonatal-associated Th2-dominated immune status, while the microbiome develops into an adult-like steady state ( 12–14 ).…”

Section: Introductionmentioning

confidence: 99%

Butyrate interacts with the effects of 2’FL and 3FL to modulate in vitro ovalbumin-induced immune activation, and 2’FL lowers mucosal mast cell activation in a preclinical model for hen’s egg allergy

Zuurveld,

Diks,

Kiliaan

et al. 2023

Front. Nutr.

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BackgroundEarly life provides a window of opportunity to prevent allergic diseases. With a prevalence of 0.5–2% in infants, hen’s egg allergy is one of the most common food allergies. The immunomodulatory effects of human milk oligosaccharides (HMOs), 2′-fucosyllactose (2’FL), and 3-fucosyllactose (3FL) were studied in an in vitro mucosal immune model and an in vivo murine model for hen’s egg (ovalbumin) allergy.MethodsIntestinal epithelial cell (IEC)/dendritic cell (DC) and DC/T cell cocultures were used to expose IECs to ovalbumin (OVA) in an in vitro mucosal immune model. The effects of epithelial pre-incubation with 0.1% 2’FL or 3FL and/or 0.5 mM butyrate were studied. Three- to four-weeks-old female C3H/HeOuJ mice were fed AIN93G diets containing 0.1–0.5% 2’FL or 3FL 2 weeks before and during OVA sensitization and challenge. Allergic symptoms and systemic and local immune parameters were assessed.ResultsExposing IECs to butyrate in vitro left the IEC/DC/T cell cross-talk unaffected, while 2’FL and 3FL showed differential immunomodulatory effects. In 3FL exposed IEC-DC-T cells, the secretion of IFNγ and IL10 was enhanced. This was observed upon pre-incubation of IECs with 2’FL and butyrate as well, but not 2’FL alone. The presence of butyrate did not affect OVA activation, but when combined with 3FL, an increase in IL6 release from DCs was observed (p < 0.001). OVA allergic mice receiving 0.5% 3FL diet had a lower %Th2 cells in MLNs, but the humoral response was unaltered compared to control mice. OVA-allergic mice receiving 0.1 or 0.5% 2’FL diets had lower serum levels of OVA-IgG2a (p < 0.05) or the mast cell marker mMCP1, in association with increased concentration of cecal short-chain fatty acids (SCFAs) (p < 0.05).ConclusionIn vitro butyrate exposure promotes the development of a downstream type 1 and regulatory response observed after 2’FL exposure. 2’FL and 3FL differentially modulate ovalbumin-induced mucosal inflammation predominantly independent of butyrate. Mice receiving dietary 3FL during ovalbumin sensitization and challenge had lowered Th2 activation while the frequency of Treg cells was enhanced. By contrast, 2’FL improved the humoral immune response and suppressed mast cell activation in association with increased SCFAs production in the murine model for hen’s egg allergy.

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