The Mucosal Barrier. Part 4
It was postulated that supplementation with these specific Lactobacillus strains could benefit patients with allergic diseases by reducing Th2 cytokine production. Other studies have shown that L. rhamnosus GG can reduce allergic disease symptoms in humans. Ingestion of therapeutic levels of L. rhamnosus GG by breast-feeding mothers and newborn babies resulted in a 50% inhibition of the risk of developing atopic eczema in babies. These studies provide an example of how administration of strainspecific probiotics can modulate the immune response and down-regulate the Th2 dominance associated with the development of allergies.
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Regulatory T cells
There are other subsets of T cells, termed type 1 T regulatory cells (Treg) or Type 3 T regulatory cells (Th3) that help regulate T-helper cell functions and maintain intestinal homeostasis. For example, Treg cells predominantly secret IL-10, a cytokine that down-regulates Th1 activity and, therefore, reduces Th1-associated inflammation. Adequately primed Th3 cells primarily secrete TGF-β, which helps modulate both Th1 and Th2 activity7 (see figure 1). There is increased understanding that Treg and Th3 cells are influential in the maintenance of mucosal immunity and, therefore, the prevention of pathology. Furthermore, certain probiotic strains can moderate these regulatory responses. For example, L. paracasei (NCC2461) stimulates in vitro regulatory T cells to produce TGF-beta and IL-10, cytokines implicated in the oral tolerance response to bovine betalactoglobulin in mice.14,15 Artificial induction of the oral tolerance response, via the administration of strain-specific probiotics, would help modulate hypersensitivity reactions.
Conclusions and future directions
There are convincing initial studies with animal models and humans to demonstrate that probiotics can reduce Th1 or Th2 skewed disorders, like gastrointestinal inflammation and allergic diseases. These initial studies are encouraging but future studies must be conducted to more clearly determine the impact that specific probiotic strains have on T cells and immunopathology. Further studies also are needed to determine the therapeutic dose and timing of probiotic administration needed to produce these immune responses in humans. This increased knowledge of the effect of specific strains of probiotics on immune-system modulation has widespread medical implications. For example, when a patient has a Th1-cell dominant disorder, such as Crohn’s disease, then administration of specific probiotic strains can be given to promote secretion of IL-10 and TGF-β cytokines and, therefore, down-regulate chronic Th1 cell-associated inflammation and promote a return to balanced immunity.
An increased understanding of the unique effects of strain-specific probiotics on the immune system will help healthcare professionals be more specific with their therapeutic intent and select certain probiotic supplements based on the diagnosed condition and the desired direction needed to positively influence the immune system. Nutraceutical companies also can formulate safe, effective probiotic supplements with unique effects on the immune system that can be more effectively used to reduce pathogenesis and maintain intestinal homeostasis. Currently, there are some multistrain probiotics that are known to affect Th1- or Th2-cell associated immunity. For example, NFH ProBio SAP-90 contains a blend of probiotic strains that will cause a more balanced Th1:Th2 response, whereas HMF forte more specifically activates the Th1 pathway and thus down-regulates overactive Th2 disorders. Conversely, the probiotic mixture VSL#3 promotes secretion of cytokines that drive a Th2 response and, therefore, will prevent and treat diseases associated with Th1 cell rigidity. With future clinical trials, there will be an increased understanding of how probiotic strains can regulate the production of T cell cytokines to produce a balanced T helper cell response (Th1=Th2=Th3/Tr1) and prevent imbalance (Th1>Th2 or Th2>Th1). Ideally, a more selective choice of probiotics by healthcare professionals can be used to prevent and treat certain immunopathologies and, therefore, maintain optimal health.