Dysbacteriosis, Dysbiosis, The Gut Problems: Nutritional Products and Dietary Supplements. MegaEl-Dena

BENEFITS OF TAKING MEGAEL-DENA FOR PATIENTS WITH DYSBIOSIS

The human body is inhabited by a variety of microorganisms, mainly bacteria, most of which reside in the gastrointestinal tract; these microorganisms are referred to as the commensal microbiota (or commensal microflora). It has been estimated that the number of bacterial cells in the human body exceeds the number of our own cells by one order of magnitude [1]. Because of the complex interactions among different bacterial species and between the host and the intestinal microbiota, our digestive tract can be considered as an ecosystem [2]. Many of these microorganisms can be considered as our symbionts; their important function is to protect the host from invasion by pathogenic microorganisms, either by direct competition or via immunomodulation [3, 4].

 

Dysbiosis (dysbacteriosis) is a collective name for disturbances in the composition of the intestinal microbiota that lead to an imbalance between beneficial and harmful bacteria [5]. Potential causes of dysbiosis include the use of antibiotics, vaccinations, general antimicrobial strategies, exposure of newborns to “incorrect” sets of microorganisms in hospitals, psychological stress, and diet components; in particular, the microbiota composition is affected by the content of sulfates, sugars, proteins, and the ratio between dietary intake of proteins and fibers/indigestible starch [4, 6]. Smoking has been recently shown to be also associated with dysbiosis [7].

 

Chronic dysbiosis is associated with a number of pathological conditions, such as gastrointestinal disturbances [8], Helicobacter pylori infection [9], inflammatory bowel disease [5, 10, 11], ankylosing spondylitis [12], colorectal cancer [13, 14, 15], chronic fatigue syndrome [16], non-alcoholic fatty liver disease [17, 18], and obesity [17]. Chronic dysbiosis caused by diseases can be exacerbated by external factors. For example, smoking both causes dysbiosis in healthy subjects and exacerbates it in patients with Crohn's disease (a form of inflammatory bowel disease) [7]. Finally, genetic predisposition may also play a role in the development of dysbiosis. For example, variations in the genes related to immunity and inflammation (NOD2, IRGM, and IL23R) and autophagy (ATG16L) have been found to influence the microbiota composition [4], and gastrointestinal dysfunction in patients with cystic fibrosis (which is a genetic disease) has been found to be associated with excessive growth of Escherichia coli [19].

 

In many cases, dysbiosis is asymptomatic, or its consequences may be difficult to detect without dedicated studies. For example, a retrospective study conducted in the Netherlands examined a hypothesis about a link between dysbiosis and cervical cancer [20]. This study involved 100,605 women, including 1,439 with a fungus Candida vaginalis and 5,302 with dysbacteriosis (the rest had normal cervical smears). The authors found that dysbacteriosis but not the presence of C. vaginalis was significantly increased the risk of developing (pre)neoplastic changes.

 

One way to help correct dysbiosis is to use supplements containing probiotics, defined as “microorganisms that have a favorable influence on the host by improving the indigenous microflora” [21]. The beneficial effects of Bifidobacterium (from the phylum Actinobacteria) and Lactobacillus (from the phylum Firmicutes) are best documented and species from these two genera are most often used in probiotic formulations [22]. However, the improvement of gut microbiota by taking probiotics may be transient. 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 [23]. Since these bacteria are already present in the intestines (even if their numbers may be reduced in the case of dysbiosis), the concept of prebiotics postulates that taking these compounds would stimulate the growth of these bacteria and help normalize the microbiota. The most widely known prebiotics are non-digestible oligosaccharides, in particular fructooligosaccharides(FOS) [23].

 

The two approaches are not mutually exclusive; moreover, they can be used as complementary, leading to the concept of synbiotics, i.e. supplements containing both probiotics and prebiotics that synergistically stimulate the growth of beneficial bacteria, both endogenous and those introduced with the supplement [23, 24]. MegaEl-Dena is a synbiotic containing FOS and as many as 8 species of viable beneficial bacteria: 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.

 

Dysbiosis may also lead to serious, clinically obvious consequences. One example is neonatal necrotizing enterocolitis (NEC) in very-low-birth-weight preterm infants. NEC is an inflammatory condition characterized by necrosis of bowel tissues and is a major cause of morbidity and mortality in premature infants [25]. Although the exact causes of NEC are still a matter of debate, dysbiosis is thought to play a role. In particular, recent evidence indicates that prediagnosis fecal samples from NEC infants contain abundant Clostridium perfringens or Klebsiella sp. [26]. A recent meta-analysis of 24 studies showed that in most studies supplementation with probiotics significantly reduced the incidence of severe NEC (this effect was observed in 20 studies) and mortality (17 studies) [27]. Formulations containing either Lactobacillus species only or Lactobacillus in combination with Bifidobacterium (i.e. similar to MegaEl-Dena) were found to be most effective. No systemic infections with the probiotic species were noted in any of the analyzed studies.

 

Another pathological condition encountered in preterm newborns is systemic fungal infections, including those with Candida species (candidemia, or invasive candidiasis), the incidence of which is increased because of Candida overgrowth owing to the deficiency in the intestinal bacterial microbiota. A study conducted in Italy found that supplementation with two Lactobacillus species (used separately) significantly reduced the presence of Candida sp. in the stool as well as the incidence of late-onset sepsis and abnormal neurological outcomes [28]. Likewise, a randomized, double-blind, placebo-controlled study conducted in Finland found that consuming cheese containing probiotic bacteria suppressed oral Candida overgrowth in the elderly [29], and Lactobacillus supplementation has long been known to suppress Candida overgrowth in the vagina [30].

 

Irritable bowel syndrome and chronic idiopathic constipation have no firmly established causes (as the name of the latter condition indicates), but dysbiosis may be involved at least in some cases [31, 32, 33]. Therefore, a number of studies have attempted to use probiotics, prebiotics or synbiotics in patients with these conditions. A recent meta-analysis of 43 such randomized controlled trials found that probiotics have beneficial effects in patients with irritable bowel syndrome, including such symptoms as abdominal pain, bloating, and flatulence scores [34]. Whether prebiotics are effective alone or in combination with probiotics could not be unequivocally established because of scarcity of the data. Both probiotics and synbiotics appeared to have beneficial effects in patients with chronic idiopathic constipation, however this conclusion needs further confirmation because of a limited number of such studies [34].

 

According to the analysis by McFarland [22], probiotics are generally more efficient in patients who initially have normal intestinal microbiota but had to be subjected to a microbiota-disrupting treatment (such as antibiotic therapy) that results in dysbiosis than in patients with pre-existing chronic dysbiosis. Clinical efficacy of probiotics is associated with strains capable of correcting dysbiosis, i.e. restoring the normal microbiota [22], which confirms that beneficial effects of such supplements on the microbiota are linked to its normalization.

 

The current challenge is that in many cases the best combinations of probiotics and prebiotics for patients with particular kinds of dysbiosis are not yet defined; moreover, only a limited proportion of intestinal microorganisms can be identified by traditional culturing. In this respect, the introduction of next-generation sequencing and metagenomics [35] can be expected to yield a much more complete picture of the effects of probiotics and prebiotics on the commensal microbiota in the near future. Since precise information about the deficiencies in particular bacterial species remains unavailable in many cases of dysbiosis, the most promising option for dysbiosis correction in such cases may be using synbiotics, such as MegaEl-Dena, that contain several bacterial species.

 

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