The probiotic activity of Lactobacillus murinus against food allergy
Introduction
Considerable evidence suggests that consumption of probiotic functional foods may induce beneficial effects to ameliorate allergic responses (Kang et al, 2016, Takeda et al, 2014). Probiotic lactic acid bacteria (LAB) are considered as one of the major bioactive ingredients contained in commonly consumed functional foods for this purpose (Parvez, Malik, Ah Kang, & Kim, 2006). LAB are found in various fermented foods and are an important group of enteric bacterial flora known to have a close interaction with the gut immune system (Björkstén, 2004, Böttcher et al, 2000). Previous studies reported different profiles of enteric bacteria between allergic patients and healthy individuals (Björkstén et al, 1999, Böttcher et al, 2000). Hence, modulation of enteric bacterial composition using functional probiotics has been proposed as a strategy for themanagement of some disorders, in particular atopic diseases (Björkstén et al, 1999, Pelto et al, 1998, Tripathi, Giri, 2014).
Food allergy is an immune disorder to dietary proteins, with symptoms ranging from mild gastrointestinal symptoms to severe anaphylactic shock (Sampson, 2004). The prevalence of food allergy is approximately 6–8% in children and 1–4% in adults (Sicherer & Sampson, 2006). To date, no effective therapy targeting the immunopathology of food allergy is available, and pharmacotherapy is used primarily for the relief of hypersensitivity symptoms. The current management of food allergy mainly relies on the avoidance of relevant allergens (Tiemessen et al., 2004). Hence, the development of effective preventive and therapeutic measures for managing food allergy is of importance (Skolnick et al., 2001).
Food protein-induced allergic responses are generally primed at intestinal mucosa and the hypersensitivity reactions are triggered by the degranulation of mast cells armed with allergen-specific immunoglobulin (Ig)E (Untersmayr & Jensen-Jarolim, 2006). The class switching of IgE from IgM is primarily dictated by T helper (Th) cell-derived cytokines, in which IFN-γ and IL-4 are pivotal Th1 and Th2 cytokines that down- and up-regulate, respectively, the production of IgE. Hence, shifting immune balance from the Th2 to Th1 direction has been proposed as a strategy to correct the aberrant T cell immunity associated with food allergy (Coffman, Savelkoul, & Lebman, 1989). Key cytokines governing the development of Th1 and Th2 cells are IL-12 and IL-4, respectively. IL-12 expressed by antigen-presenting cells up-regulates Th1 cell differentiation by enhancing T-bet expression (Lighvani et al., 2001). In contrast, IL-4 induces Th2 cell differentiation by inducing GATA3 expression (Finotto et al, 2001, Zhang et al, 1999). In addition to cytokine-dependent regulations, T cell differentiation is also influenced by co-stimulatory molecules expressed by dendritic cells (DC). For example, OX40 ligand (OX40L) has been linked to the development of Th2-related allergic responses (Blázquez, Berin, 2008, Chu et al, 2014, Gauvreau et al, 2014).
Several strains of enteric bacteria with probiotic activities are effective to ameliorate allergic responses via various immunological mechanisms, such as the enhancement of Th1 or regulatory T (Treg) cell functions depending on different bacterial strains (Ashraf et al, 2014, Frossard et al, 2007, Lyons et al, 2010, Shida et al, 1998, Yasuda et al, 2008). We previously reported that Lactobacillus murinus was one of the major enteric strains sensitive to the prebiotic effect of diosgenin, a plant-derived steroidal sapogenin exhibiting anti-allergic and immunomodulatory properties. (Huang et al, 2012, Huang et al, 2009, Huang et al, 2010). Interestingly, the underlying mechnism for diosgenin-mediated anti-allergic effects resembles that of certain probiotic LAB, in that the functionality of both Th1 and Treg cells is upregulated. Although L. murinus has been previously reported capable of colonizing in the gastrointestinal tract (Gardiner et al, 2004, Perelmuter et al, 2008), it is currently unclear if it possesses anti-allergic activity. Hence, the objective of the present study is to test our hypothesis that L. murinus may be a functional probiotic possessing anti-allergic and immunomodulatory activities.
Section snippets
Chemicals and reagents
Reagents, standards and antibodies used for ELISA were purchased from BD Biosciences (San Jose, CA, USA). All the buffer, broth, agar and anaerobe container system used for bacterial incubation were purchased from BD Biosciences (San Jose, CA, USA). Reagents and enzymes used for RT-PCR were purchased from Promega (Madison, WI, USA). Reagents and antibodies used for immunohistochemical staining were purchased from AbCam (Cambridge, MA, USA), BioGenex Laboratories (San Ramon, CA, USA) and
Effects of L. murinus on the density of enteric bacterial flora
We firstly examined if oral administration with L. murinus affected the profile of enteric bacteria in mice with food allergy. The density of faecal LAB and non-specific bacteria was examined before and after the 5th OVA challenge. Before OVA challenge, the density of LAB and non-specific bacteria is comparable between non-sensitized and OVA-sensitized mice (Fig. 2; NS vs. OVA). Administration with L. murinus increased the density of LAB, but not non-specific bacteria (Fig. 2; L. murinus vs.
Discussion
Results from the present study confirm our hypothesis that L. murinus is a functional probiotic possessing anti-allergic activities in vivo. Several lines of evidence substantiates this conclusion. First, oral administration with L. murinus restored the deteriorated profile of intestinal bacterial flora in allergic mice. Second, L. murinus administration attenuated allergic responses, including the occurrence of allergic diarrhoea, mast cell activation, and serum IgE production. Third, the
Conclusions
Our data confirm the hypothesis that L. murinus is a functional probiotic against food allergy. To the best of our knowledge, the present study provides the first evidence to demonstrate the anti-allergic effect of L. murinus in vivo. Mechanistic investigation revealed that the expression of both IL-12 and OX40L by intestinal DC was modulated by L. murinus to promote intestinal Th1 immunity and attenuate allergic responses. These findings suggest that L. murinus may be used as a functional
Conflict of interest
The authors declare no conflicts of interest relevant to this work.
Acknowledgement
This work was supported by Grant 104-2320-B-002-024-MY3 from the Ministry of Science and Technology, Taiwan.
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