Probiotics for patients Undergoing Chemotherapy, Radiotherapy. Probiotics and prebiotics for patients taking antibiotics. MegaEl-Dena

BENEFITS OF TAKING MEGAEL-DENA FOR PATIENTS UNDERGOING ANTIBIOTIC THERAPY, CHEMOTHERAPY, AND RADIOTHERAPY

Some types of therapy, especially antibiotic therapy as well as chemotherapy and radiotherapy in cancer patients, can directly or indirectly damage the intestinal microbiota. Although antibiotics are intended to kill pathogenic bacteria, they reduce the total number of bacteria and cause changes in microbiota composition (dysbiosis); these changes are transient in most cases but may occasionally last for several months [1]. In particular, in babies and infants, antibiotic therapy has been reported to cause dramatic shifts in both the total numbers and composition of intestinal microbiota [2]. Antibiotic treatment can reduce bacterial abundance in babies’ feces (used as a proxy for the abundance of intestinal microbiota) by as much as six orders of magnitude, but the dynamics of the microbial species composition differs in different babies [2].

The intestinal microbiota protects the human body from pathogenic microorganisms by direct competition with them and by immunomodulation [3, 4]. The latter mechanism may be particularly important because approximately 70% of immune system cells are located in the gastrointestinal tract [5]. Beneficial bacteria may directly interact with intestinal epithelial or immune cells of the host through specific receptors and produce bioactive compounds that act as immune modulators [3, 4, 6]. Disruption of the normal intestinal microbiota may allow propagation of harmful microorganisms such as pathogenic bacteria (like Clostridium difficile) or fungi (Candida species); these complications are considered in detail below.

One way to help correct disturbances in the intestinal microbiota is to take probiotics and/or prebiotics. Probiotics are defined as “microorganisms that have a favorable influence on the host by improving the indigenous microflora” [7], whereas prebiotics are substances that are non-digestible for humans but stimulate the growth of beneficial bacteria [8]. MegaEl-Dena contains both prebiotics (fructooligosaccharides FOS) and probiotics and therefore is called a synbiotic. MegaEl-Dena contains 8 species of viable beneficial bacteria, including four species of Bifidobacterium (B. bifidum, B. breve, B. lactis, and B. longum), three species of Lactobacillus (L. acidophilus, L. casei, and L. rhamnosus), and Streptococcus thermophilus.

In particular, the ability of probiotics to regulate human immunity is illustrated by a study that involved healthy volunteers, which found that supplementation with lactic bacteria (L. acidophilus, L. casei, and L. rhamnosus) for seven weeks resulted in changes in the expression of genes involved in regulatory networks that control immunity and mucosal homeostasis [9]. Multiple clinical studies have documented the beneficial effects of probiotics and/or prebiotics for patients undergoing antibiotic therapy, chemotherapy, or radiotherapy.

Fungal infections

Disruption in the intestinal microflora caused by the use of broad-spectrum antibiotics may promote, by an as yet poorly understood mechanism, excessive colonization of intestinal mucosa by fungi, in particular Candida species [10]. This colonization is a risk factor for invasive candidiasis, a systemic life-threatening infection, which is most frequent in immunocompromised, severely ill, and pediatric patients [10, 11,12]. Since probiotics help to restore endogenous microflora, they can be expected to be beneficial for the prevention of Candida infections. Indeed, supplementation with Lactobacillus, in particular L. acidophilus (one of the components of MegaEl-Dena), has long been known to prevent and suppress Candida overgrowth in the vagina [13, 14].

More recently, Kumar and colleagues [15] investigated the effect of a synbiotic similar in composition to MegaEl-Dena (but also containing yeast) in children treated with broad-spectrum antibiotics. The authors found that the prevalence of Candida colonization was reduced by 34–37% in the group that received the synbiotic in comparison with the placebo group, and concluded that probiotics could be useful to reduce gastrointestinal Candida colonization [15].

Antibiotic-associated diarrhea

Diarrhea is a serious symptom of microbiota damage, as it may lead to dehydration and malnutrition, and in severe cases to cardiovascular compromise and death [6]. Sometimes the use of antibiotics leads to the prevalence of the harmful bacterium C. difficile, which may cause antibiotic-induced diarrhea (AAD). Antibiotic therapy is one of the three major risk factors for C. difficile infections (the other two being immunosuppression and old age) [17], which are often considered together with AAD.

An analysis of 16 studies (3,432 participants in total) concluded that, of several probiotic species tested, administration of L. rhamnosus (a component of MegaEl-Dena) or Saccharomyces Boulardii, simultaneously with antibiotics, was associated with a reduced risk of AAD onset [18]; other combinations, such as B. lactisand S. thermophilus (both are components of MegaEl-Dena), may be also beneficial [19]. A randomized double-blind placebo-controlled trial that involved elderly hospital patients taking antibiotics found that consumption of a drink containing S. thermophilus, L. casei, and another lactobacterium during and after antibiotic therapy was associated with a reduced incidence of AAD and C. difficile-associated diarrhea [20]. No serious adverse effects of probiotics have been reported in AAD patients.

There is also some evidence for beneficial effects of prebiotics and synbiotics in patients with AAD/C. difficile-induced diarrhea. A randomized clinical trial of treatment of C. difficile infection with specific antibiotics conducted in the UK found that taking FOS was associated with increased counts of bifidobacteria and significantly fewer relapses [21]. A placebo-controlled study conducted in Sweden compared the effects of probiotics (L. acidophilus and B. longum) and a corresponding synbiotic (the above bacterial species supplemented with FOS) on healthy volunteers subjected to antibiotic treatment. The authors found that C. difficile could be isolated after antibiotic treatment at a similar rate from the stool of patients who received placebo and probiotics, but at a much lower rate from that of patients who received the synbiotic [22]. The authors also found that L. acidophilus (but not B. longum) efficiently colonized the intestines.

A recent meta-analysis of 82 clinical trials, which included 11,811 participants, concluded that there is a statistically significant association between the intake of probiotics and reduction in AAD, although the effects of combinations of particular probiotics and antibiotics need further investigation [23]. An independent meta-analysis of 34 randomized double-blinded placebo-controlled trials (4,138 patients in total) found that the pooled relative risk of AAD was reduced by ~50% by probiotic supplementation [24]. These studies also did not report any adverse effects of probiotics.

Diarrhea induced by chemotherapy and radiotherapy

According to the Physician Data Query database of the NIH National Cancer Institute [25], on average 14% of cancer patients undergoing chemotherapy experience moderate-to-severe diarrhea. According to other estimates, the overall incidence of chemotherapy-induced diarrhea (CID) in cancer patients is 20%–40% [26]. The incidence of diarrhea can be as high as 50%–80% with some chemotherapeutic regimens, in particular those containing fluoropyrimidines or irinotecan [25, 26]. Diarrhea occurs in 60% of patients (with 10% having severe diarrhea) undergoing chemotherapy with tyrosine kinase inhibitors and antibodies and may interfere with the efficiency of chemotherapy [16]. Pathophysiology of CID is far from clear but is thought to involve the loss of intestinal epithelium, impaired water absorption in the colon and changes to the intestinal microbiota [26].

Taking probiotics is recommended as one of several measures to help prevent CID [16], although the evidence for their efficiency is mainly preclinical with so far only one randomized clinical study conducted in Finland, which involved 150 colorectal cancer patients who received two different regimens of 5-fluorouracil (fluoropyrimidine-based chemotherapy) following surgery; some patients received L. rhamnosus supplementation and fiber during chemotherapy [27]. The study found that L. rhamnosus supplementation did not affect the overall toxicity of chemotherapy but was associated with a reduced frequency of grade 3 or 4 diarrhea and less abdominal discomfort. No toxicity associated with the supplement was noted. Limitations of this study were that it was neither placebo-controlled nor blinded. The same authors are now conducting a prospective, multicenter, randomized, double-blind, placebo-controlled study (ClinicalTrials.gov identifier: NCT00197873), the results of which should be available soon.

Radiotherapy-induced diarrhea occurs in 50% of cancer patients undergoing pelvic or abdominal radiotherapy [28]. An early small-scale study (24 patients) conducted in Finland found that L. acidophilus supplementation in patients with gynecological malignancies undergoing pelvic or abdominal radiotherapy was associated with a significant reduction in radiotherapy-associated diarrhea [29]. These early findings have been more recently supported by other studies; in particular, the beneficial effect of probiotics may be more pronounced when they are administered simultaneously with radiotherapy as opposed to administration after radiotherapy [25, 30].

Thus, several components of MegaEl-Dena are expected to have beneficial effects for patients undergoing antibiotic therapy - L. rhamnosus, B. lactis, and S. thermophilus, as well as FOS, chemotherapy - L. rhamnosus, and radiotherapy - L. acidophilus.

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