Immunomodulatory Effects of Escherichia coli ATCC 25922 on Allergic Airway Inflammation in a Mouse Model

Abstract

BackgroundHygiene hypothesis demonstrates that the lack of microbial exposure would promote the development of allergic airway disease (AAD). Therefore, the gut microbiota, including Escherichia coli (E. coli), would probably offer a potential strategy for AAD.ObjectiveTo investigate whether E. coli infection is able to suppress the induction of AAD and to elucidate the underlying mechanisms.MethodsNonpathogenic E. coli ATCC 25922 was infected by gavage before AAD phase in three patterns: 108 or 106 CFU in neonates or 108 CFU in adults. Then mice were sensitized and challenged with ovalbumin (OVA) to induce allergic inflammation in both the upper and lower airways. Hallmarks of AAD, in terms of eosinophil infiltration and goblet cell metaplasia in subepithelial mucosa, Th2 skewing of the immune response, and levels of T regulate cells (Tregs), were examined by histological analysis, ELISA, and flow cytometry, respectively.Results E. coli, especially neonatally infected with an optimal dose, attenuated allergic responses, including a decrease in nasal rubbing and sneezing, a reduction in eosinophil inflammation and goblet cell metaplasia in subepithelial mucosa, decreased serum levels of OVA-specific IgE, and reduced Th2 (IL-4) cytokines. In contrast, this effect came with an increase of Th1 (IFN-r and IL-2) cytokines, and an enhancement of IL-10-secreting Tregs in paratracheal lymph nodes (PTLN).Conclusion E. coli suppresses allergic responses in mice, probably via a shift from Th1 to Th2 and/or induction of Tregs. Moreover, this infection is age- and dose-dependent, which may open up novel possibilities for new therapeutic interventions.

Dietary Fiber Intake Regulates Intestinal Microflora and Inhibits Ovalbumin-Induced Allergic Airway Inflammation in a Mouse Model

“…In addition, Lactobacillus and Bifidobacteriumare , as typical probiotic bacteria, enable the homeostasis of immune cells and decrease the susceptibility to allergic inflammation, well-supported by a mounting body of evidences [ 10 , 11 , 39 – 44 ]. Furthermore, the beneficial effect of E. coli against allergic diseases has also been confirmed in other animal studies [ 26 , 45 – 46 ]. As Maslowski [ 35 ] argued, if diet affects the composition of microbiota, and the microbiota regulates immune and inflammatory responses, then diet changes should have easily quantifiable effects on the immune response.…”

“…However, the regulatory mechanisms, as well as the level of impact of dietary fiber against AAD, were still unclear. Therefore, herein we developed a new mouse model with allergic rhinitis and asthma inducted by ovalbumin (OVA), based on the common pathologies and mechanisms shared in upper and lower airway [ 1 , 2 , 26 ]. The model exhibited frequent nasal rubbing and sneezing, abundant inflammatory cell infiltration into the nasal mucosa and the lung and excessive Th2 skewing of the immune responses.…”

Reduced airway microbiota diversity is associated with elevated allergic respiratory inflammation

“…21 Interestingly, the SPF rats, which had less bacterial diversity in the airway, showed significantly increased nasal symptoms after the OVA challenge compared with the control rats, suggesting that the decreased diversity of commensal bacteria in the airway increased sensitization to OVA. In addition, the SPF rats exhibited increased counts of lymphocytes in BALF and more abundant inflammation infiltration in the lung tissues.…”

The influence of the young microbiome on inflammatory diseases—Lessons from animal studies

“…Helicobacter pylori seems to be negatively correlated to ARD in humans and eradication of H. pylori with antibiotics, especially early in life, could in part explain the increasing prevalence of ARD in humans (Blaser and Reibman, ; Blaser, ). The protective effect of H. pylori , and also Escherichia coli , has been confirmed in animal studies—mice receiving a nonpathological infection with these species early in life were protected against ARD through activation of regulatory T cells (Hunt et al, ; Arnold et al, ; Pang et al, ).…”