Probiotic and prebiotic MegaEl-Dena for immune system support

BENEFITS OF TAKING MEGAEL-DENA AS AN IMMUNOMODULATOR

Beneficial microorganisms, predominantly bacteria, which inhabit the gastrointestinal tract (collectively called commensal microbiota, or commensal microflora), protect our bodies from invasion by pathogenic microorganisms, either by direct competition with pathogens or via immunomodulation [1,2]. The latter mechanism may be particularly important because approximately 70% of immune system cells are located in the gastrointestinal tract [3]. Beneficial bacteria are also thought to enhance the epithelial barrier, which separates the content of the gastrointestinal tract with a multitude of microorganisms from the cells of the immune system located underneath the intestinal epithelium [4].

Disturbances in the composition of the intestinal microbiota that lead to an imbalance between beneficial and harmful bacteria, which are called dysbiosis (or dysbacteriosis), are associated with several immunological disorders, including inflammatory bowel disease, a group of inflammatory conditions mainly affecting the colon and small intestine [5-7]. One of the major types of inflammatory bowel disease is ulcerative colitis, continuous mucosal inflammation limited to the colon with common symptoms such as bloody diarrhea and abdominal pain [8,9].

Multiple regulatory mechanisms mediate the communication between the commensal microbiota and host. Bacteria may directly interact with intestinal epithelial or immune cells through specific receptors and can also produce bioactive compounds that act as immune modulators [1,2,10]. One of the mechanisms of immunomodulatory activities of beneficial bacteria appears to involve Toll-like receptors, the same receptors that are involved in recognition of danger signals from potential pathogens and initiating the inflammatory response [11]. The mechanism of action of bioactive compounds produced by the commensal microbiota may involve regulation of cytokine secretion through the NFκB and MAPK signaling pathways, which in its turn regulates proliferation and differentiation of immune cells. The ability of the microbiota to regulate human immunity is illustrated by a study that involved healthy volunteers, which found that supplementation with lactic bacteria (Lactobacillus acidophilus, L. casei, and L. rhamnosus) for 7 weeks resulted in changes in the expression of genes involved in regulatory networks that control immunity and mucosal homeostasis [12]. Host epithelial cells, in their turn, produce compounds and signals (such as fucosylated cell surface proteins) that are recognized and metabolized by commensal bacteria [13]. Normally, the commensal microbiota is tolerated by the host and does not provoke an immune response. Altered microbiota composition and function is thought to provoke increased immune stimulation, and abnormal immune responses to the commensal microbiota may be one of the mechanisms that underlie the development of inflammatory bowel disease [14].

One way to help correct disturbances in the intestinal microbiota is to use supplements containing probiotics, defined as “microorganisms that have a favorable influence on the host by improving the indigenous microflora” [15]. Another way to modulate the intestinal microbiota is supplementation with so-called prebiotics, i.e. food ingredients that are non-digestible for humans but stimulate the growth of beneficial bacteria [16]. Formulations that contain both probiotics and prebiotics are called synbiotics. MegaEl-Dena is a synbiotic: it contains prebiotics (FOS) and probiotics, i.e. 8 species of viable beneficial bacteria, including 4 species of Bifidobacterium (B. bifidum, B. breve, B. lactis, and B. longum), 3 species of Lactobacillus (L. acidophilus, L. casei, and L. rhamnosus), and Streptococcus thermophilus. Probiotics are known to have beneficial effects on immunity, both at the molecular and cellular levels. Thus, they can be used to help correct immunological disorders such as ulcerative colitis. These aspects are described below.

Effect of probiotics on cytokine and immunoglobulin production

A Japanese study that used 60 healthy volunteers found that administration of a Lactobacillus species resulted in a statistically significant increase in interferon-α in 2–4 weeks depending on the dose [17]. The authors also compared viable and heat-killed bacteria and found that this effect required viable bacteria [17]. Similarly, a later study by Arunachalam and colleagues [18] conducted in Canada used B. lactis administration in elderly healthy volunteers and found a significant increase (in comparison with the placebo group) in the levels of interferon-α after 6 weeks of taking the probiotic. Intake of L. rhamnosus was reported to reduce the production of intestinal tumor necrosis factor (TNF)-α, which is a proinflammatory cytokine [19].

A number of studies have documented the ability of probiotics to stimulate the production of immunoglobulin A (IgA), which plays a critical role in mucosal immunity [20,21]. Intake of B. bifidum and L. acidophilus was reported to increase the IgA levels in subjects receiving attenuated Salmonella typhi to mimic an enteropathogenic infection; the increase was observed both in IgA specific to the pathogen and in total serum IgA [22]. Similarly, in children, the intake of L. caseiin parallel with rotavirus vaccination [23] or intake of L. rhamnosus or L. casei during rotavirus-induced diarrhea [24,25] stimulated IgA production. Similar observations have been reported for bifidobacteria: Fukushima and coworkers found that the intake of B. lactis increased the levels of both total and pathogen-specific IgA upon anti-poliovirus vaccination in healthy children [26]. In a more recent study, consumption of Bifidobacterium-containing yogurt was found to be associated with an increase in the levels of serum IgA and reduction of those of the pro-inflammatory cytokine interleukin (IL)-6, suggesting immunostimulatory and anti-inflammatory effects [27]. An anti-inflammatory effect of probiotics was also documented by Pessi and coworkers [28], who found that L. rhamnosusadministration in children with atopic allergy increased the serum level of the anti-inflammatory cytokine IL-10 but did not affect the levels of several pro-inflammatory cytokines, and by Hart and coworkers who found that bifidobacteria inhibit production of interferon-γ [29]. Thus, these studies indicate that different combinations of probiotic species may stimulate immune responses and/or suppress inflammation.

Effect of probiotics on immune cells

An enhanced ex vivo phagocytosis-mediated bactericidal activity of polymorphonuclear leukocytes was observed in healthy elderly volunteers after 6 weeks of supplementation with B. lactis in a Canadian study [18]. A similar study conducted in New Zealand, which also used B. lactis supplementation in healthy elderly volunteers, confirmed this finding for polymorphonuclear leukocytes and extended it to monocytes [30]. Furthermore, the authors noted an increase in the total, helper (CD4+), and activated (CD25+) T lymphocytes and natural killer cells in the probiotic group in comparison with the placebo group as well as increased ex vivo tumoricidal activity of natural killer cells [30]. To what extent these ex vivo findings reflect the in vivo situation remains unclear [31].

The effects of probiotics on T helper cells, in particular on the balance between Th1 and Th2 cells, are well documented (reviewed by Delcenserie and colleagues [31]). Th1 cells produce pro-inflammatory cytokines (including interferon-γ and TNFα mentioned above) involved in responses to bacterial and protozoan pathogens, and are also involved in inflammatory autoimmune disorders, whereas Th2 cells stimulate production of antibodies against parasites such as worms, and are also involved in allergies [32]. The balance between Th1 and Th2 cells is influenced by dendritic cells. Using an ex vivo approach, Hart and colleagues found that exposure of human dendritic cells to a probiotic containing a mixture of several species (similar to MegaEl-Dena) reduced LPS-induced production of the pro-inflammatory cytokine IL-12, whereas production of anti-inflammatory IL-10 remained unaffected, suggesting that probiotics would shift the Th1/Th2 balance towards Th2 [29]. However, Mohamadzadeh and coworkers [33] found that exposure of LPS-challenged human dendritic cells to a mixture of several Lactobacillus strains induced high level of secretion of IL-12 and IL-18, but not IL-10, indicating a shift towards Th1. These contrasting results suggest that the effects of probiotics on fine tuning of the Th1/Th2 balance is likely to be species-specific. In some cases, probiotic stimulate both Th1 and Th2 responses [31].

Ulcerative colitis

Several studies that used either probiotics or synbiotics (some similar in composition to MegaEl-Dena) found that the intake of these supplements was associated with positive effects on the induction and/or maintenance of remission in ulcerative colitis (reviewed by Isaacs and Herfarth [34] and Haller and colleagues [35]). A more recent review of the published studies concluded that probiotics have beneficial effects in patients with mild to moderate ulcerative colitis and help to induce and maintain remission and to prevent pouchitis [36].

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