Probiotic treatment during neonatal age provides optimal protection against experimental asthma through the modulation of microbiota and T cells

Abstract

The incidence of allergic diseases, which increased to epidemic proportions in developed countries over the last few decades, has been correlated with altered gut microbiota colonization. Although probiotics may play a critical role in the restoration of gut homeostasis, their efficiency in the control of allergy is controversial. Here, we aimed to investigate the effects of probiotic treatment initiated at neonatal or adult ages on the suppression of experimental ovalbumin (OVA)-induced asthma. Neonatal or adult mice were orally treated with probiotic bacteria and subjected to OVA-induced allergy. Asthma-like symptoms, microbiota composition and frequencies of the total CD4+ T lymphocytes and CD4+Foxp3+ regulatory T (Treg) cells were evaluated in both groups. Probiotic administration to neonates, but not to adults, was necessary and sufficient for the absolute prevention of experimental allergen-induced sensitization. The neonatally acquired tolerance, transferrable to probiotic-untreated adult recipients by splenic cells from tolerant donors, was associated with modulation of gut bacterial composition, augmented levels of cecum butyrate and selective accumulation of Treg cells in the airways. Our findings reveal that a cross-talk between a healthy microbiota and qualitative features inherent to neonatal T cells, especially in the Treg cell subset, might support the beneficial effect of perinatal exposure to probiotic bacteria on the development of long-term tolerance to allergens.

Dysbiosis of the gut and lung microbiome has a role in asthma

“…The offspring showed reduced expression of TNF-α, IFN-γ, IL-5, and IL-1 in splenocytes, and reduced allergic airway and peribronchial inflammation in the lung [146]. In a recent OVA-induced asthma mouse model, probiotic oral treatment with combined Lactobacilli casei/lactis/acidophilus plus Bifidobacteria bifidium/lactis reduced allergic airway disease when given perinatally [147]. In gut microbiota, higher Firmicutes and Actinobacteria appeared when probiotics were applied at neonatal age, accompanied by higher CD4+ Tregcell numbers in BALF and increased caecal butyrate, whereas only Actinobacteria were significantly higher compared to sham-treated mice when probiotics were applied to adult animals.…”

The crosstalk between microbiome and asthma: Exploring associations and challenges

“…Mice studies showed that administration of Bifidobacterium breve or adolescentis strains and Lactobacillus plantarum or rhamnosus strains significantly decreased allergic airway inflammation in OVA‐ or birch pollen‐induced asthma mice models . It is worthy to note that the effect of pro‐biotics in mice asthma models is more prominent in neonates than adults …”

Probiotics against airway allergy: host factors to consider

“…After sensitization, a challenge step induces allergic inflammation, which involves re-exposure of the animal to the allergen via the administration route typical for a given allergic disease. For instance, in allergic airway disease models, an inflammatory response is evoked in the airways by repeated exposures (or challenges) to the allergen, through either aerosol inhalation ( Mendes et al, 2017 ; Pellaton et al, 2012 ) or intranasally ( Nunes et al, 2018 ; Wu et al, 2016 ). We list examples of such models in Table 1 .…”

“…This release of pro-inflammatory mediators in the airways also leads to airway hyperreactivity (AHR; Box 1 ), hypersecretion of mucus, airway tissue remodelling and other manifestations reminiscent of asthma-associated chronic allergic airway inflammation in humans ( Nials and Uddin, 2008 ). As a result, allergic airway inflammation is typically assessed based on differential counts of inflammatory cells, such as eosinophils and neutrophils, in the bronchoalveolar lavage fluid (BALF; Box 1 ) ( Jan et al, 2012 ; Karimi et al, 2009 ; Nunes et al, 2018 ; Pellaton et al, 2012 ) ( Table 1 ). Airway function is assessed based on airway resistance measurements with invasive ( MacSharry et al, 2012 ) and noninvasive (e.g.…”

“…whole-body plethysmography; Box 1 ) ( Jan et al, 2012 ; Karimi et al, 2009 ; Wu et al, 2016 ) techniques to assess changes in AHR. In addition, histopathological evaluation of the airways is typically performed, with Haematoxylin and Eosin staining to examine the degree of inflammatory cell infiltration and periodic acid–Schiff (PAS) staining ( Box 1 ) to assess mucus production ( Karimi et al, 2009 ; Nunes et al, 2018 ).…”