Atractylodes Japonica Rhizome Extract Fermented with a Plant-Derived Lacticaseibacillus paracasei (Lactobacillus paracasei) IJH-SONE68 Improves the Wheat Gliadin-Induced Food Allergic Reaction in Mice

There are no significant progresses in grasping the role of LABs and other beneficial microbes in a wheat-induced imbalance in the mucosal ecosystem. In general, food-derived protein-induced allergic reactions are initiated in the intestinal mucosa, where the immune response is accompanied by mucosal disease, intestinal tissue damage, and cytokine production [39]. In addition to host gastrointestinal cells, imbalances in the gut microbiota of patients with allergic diseases have been widely reported, such as decreases in Lactobacillaceae, Synechococcus, and Clostridium, and changes in intestinal microbiota diversity . Overall, probiotics have been noted as potential alternative therapies. Current reports suggest that probiotics may contribute to intestinal barrier function repair, intestinal flora restoration, antigen modification, and systemic immune modulation. However, the exact anti-allergic mechanisms of probiotic therapy have not been fully understood, which limits their broader clinical applications. Therefore, further research is needed to identify specific beneficial microbes like probiotics for different types of allergies 

For understanding the mechanisms of sensitization and allergic symptom induction, relevant animal models may help us. Because the murine immunology has been well understood and well characterized, a mouse model has been widely used to study the immune responses to Th1, Th2, or Th17 phenotypes. Schematically, IL-4 and IL-13 secreted by Th2 cells induce IgE production in mice, whereas IFN-γ secreted by Th1 cells induces T cell–mediated immunity and down-regulates Th2 cells . Th17 cells have been described as being associated with autoimmune diseases . BALB/c mice, which are a Th2-biased strain with high IgE response, have been widely used for sensitization to food allergens to obtain specific IgE responses after intragastric and intraperitoneal administration. The administration of bovine β-lactoglobulin or ovalbumin into BALB/c mice induces IgE responses that are specific to the same epitopes involved in allergy patients . This strain has also been used to study the early and late stages of anaphylaxis after intraperitoneal sensitization. Relationships between the structural characteristics of the protein and the pathophysiology of allergic reactions have been clarified .

Although the spleen is the largest lymphoid organ, it plays multiple roles in interacting with various blood cells . The systemic blood in the body directly interacts with the spleen, where it is continuously monitored by immune cells. As a result, both innate and adaptive immune responses are initiated in the spleen. During an immune response, the activation of T and B cells cause the proliferation of splenic cells, resulting in the spleen enlargement [59]. The spleen enlargement was also often observed in not only mice suffered from inflammatory disorders but also food allergy model mice, indicating that an excess immune response may lead to abnormal spleen size. In the present study, gliadin-sensitized mice showed the increase in spleen size, however, the size was reduced in accordance with anaphylaxis score by administration of fermented-AJR extract. Therefore, the LAB-fermented AJR extract may modulate immune responses.

AJR, a herbal medicine traditionally used for digestive disorders and rheumatism, is composed of a few essential ingredients, including sesquiterpenes, phenolic acids, and polyethylene alkynes . For instance, atractylodin, which is a polyethylene alkyne component of A. japonica, has been found to improve intestinal inflammation by regulating mitogen-activated protein kinase (MAPK) and reduce acute lung injury by inhibiting nucleotide binding domain-like receptor protein 3 inflammasome and Toll-like receptor 4 activation [63,64,65,66,67,68]. Recent studies have shown that atractylodin ameliorates collagen-induced arthritis in mice by modulating the maturation of dendritic cells. Additionally, it has been reported that atractylodin suppresses the Th2 response by regulating dendritic cells, leading to a decrease in the concentration of IL-4. As a result, the Th1 response is promoted followed by increasing the concentration of IFN-γ . On the other hand, it has been reported that the oral administration of IJH-SONE68 strain–derived EPS inhibits the acceleration of IL-4 and serum IgE expression in model mice with delayed-type allergies.

The fermented AJR extract contains soluble components of IJH-SONE68 strain cells including those released after sterilization, thus there are possibilities that those components might influence the outcomes of the animal experiment. However, previous studies have confirmed that the observed anti-inflammatory effects and immunomodulatory activities of IJH-SONE68 strain are primarily attributed to the EPS. Therefore, to confirm whether the EPS is also produced in the fermented AJR extract, we have measured and compared the polysaccharides’ contents purified from the AJR extract before and after fermentation with the IJH-SONE68 strain (1.1 ± 0.2 and 1.0 ± 0.3 mg yields from 5 mL samples, respectively) . The result shows that the production of EPS was not satisfactory during the fermentation of the AJR extract, indicating that the ameliorative effects on gliadin-induced allergic model mice observed in the present study may be due to specific metabolites produced during fermentation rather than EPSs. In fact, unlike the fermented AJR extract, the EPS derived from the IJH-SONE68 strain exhibited its anti-inflammatory effect not through Th1 upregulation but through Th2 downregulation .