13 februari 2012: Klik hier voor veel meer informatie over probiotica - melkzuurbacteriën en synbiotica

14 juni 2011: ik ben kanker-actueel aan het herzien en kwam dit artikel tegen over effect van preventief gebruik van probiotica vooraf aan bestralen. De uitkomsten van deze gerandomiseerde studie, al uit 2002, zijn dermate positief en goed onderbouwd in een gerandomiseerde studie dat ik dit artikel laat staan.

Mei 2002:

Een gerandomiseerde studie onder 190 mensen heeft aangetoond dat bepaalde probiotica, (melkzuurbacteriën) in veel gevallen diarree en andere darmklachten voorkomt indien dagelijks als aanvulling gegeven aan patiënten die een bestraling ondergaan. Daardoor heeft zelfs geen enkele van de patiënten die de probiotica nam zijn/haar bestralingskuur moeten onderbreken en kregen in vergelijking met de controlegroep die een placebo kregen veel en veel minder diarree en andere darmklachten voor. Ik heb nu geen tijd dit artikel te vertalen, maar hoop snel iemand te vinden die dat wel wil doen. Maar dat probiotica een hulp is bij het herstel van de darmflora wordt ook in deze studie weer bewezen. Zie voor meer informatie over probiotica, bv. wat het precies is en waar te bestellen op informatie over probiotica. Of lees eens het verhaal van Ed die genezen is van de ziekte van Crohn door dieet en suppletie en waar probiotica een grote rol in speelde.

Ik moet er wel bij aantekenen dat de onderstaande studie en publicatie is gedaan door een bedrijf dat o.a. deze probiotica zelf produceert. Wat niet wegneemt dat de studieresultaten overeenkomen met eerdere studies die zijn gedaan naar het effect van probiotica en als literatuur zijn toegevoegd. 

Prevention of Radiation-Induced Diarrhea With the Use of VSL#3, a New High-Potency Probiotic Preparation

TO THE EDITOR: Acute radiation-induced diarrhea is a common and potentially severe complication in cancer patients treated with radiotherapy. Attempts to treat this complication with antibiotics, anti-inflammatory drugs, and hyperbaric oxygen had inconclusive results, and failure of treatment occurred in a substantial proportion of patients (1).
Previous studies have shown that VSL#3, a new high-potency preparation of probiotic lactobacilli, may effectively modulate intestinal inflammation through altering the composition and the metabolic and functional properties of enteric flora (2). We hypothesized that pre-emptive treatment with VSL#3 may decrease the rate and severity of radiation-induced diarrhea during adjuvant radiotherapy after surgery for abdominal and pelvic cancer.
One hundred ninety consecutive patients attending the outpatient clinics of the Cancer X-Ray Unit of the University of Messina, Italy, who had adjuvant postoperative radiotherapy
after surgery for sigmoid, rectal, or cervical cancer were randomly assigned treatment with VSL#3 (VSL Pharmaceuticals, Fort Lauderdale, MD), one sachet t.i.d.,or placebo starting from the first day of radiation therapy. The design of the study was approved by the Ethics Committee at our hospital, and all patients gave written and informed consent to participate. The study was performed in accordance with the Declaration of Helsinki and with standards of good clinical practice.
Each sachet of VSL#3 contained 450 billions/g of viable lyophilized bacteria, including four strains of lactobacilli (L.casei, L. plantarum, L. acidophilus, and L. delbruekii subsp.
bulgaricus), three strains of bifidobacteria (B. longum, B. breve, and B. infantis), and one strain of Streptococcus salivarius subsp. thermophilus. Patients were eligible for inclusion if they had no contraindication to probiotic or antibiotic therapy or radiation therapy. We excluded from randomization patients with a Karnofsky performance score 70, a life expectancy 1 yr, persistent vomiting or diarrhea, fistulizing disease, known
Crohn’s disease or ulcerative colitis, intra-abdominal abscesses or fever (more than 37.5°C) at the time of enrollment, or clinical, microbiological, or imaging evidence ofsepsis syndrome, and requirement for continuous antibiotic treatment or use of antibiotics in the last 2 wk before initiation of VSL#3 therapy.
At baseline, patients provided a medical history and had a physical examination (consisting of vital signs, 12-lead electrocardiogram, neurological examination, and laboratory
testing). Study subjects were followed-up weekly during the scheduled cycle of radiation therapy and then 1 month after completion of radiation therapy. At each visit, clinical disease symptoms, concomitant medications, andany adverse events were reviewed, and a physical examination and laboratory studies performed.
Efficacy endpoints were incidence and severity of radiation-induced diarrhea, number of patients who discontinued radiotherapy because of diarrhea, daily number of bowel movements, and the time from the start of the study to the use of loperamide as rescue medication for diarrhea.
The randomization was balanced between treatment groups in terms of sex, age, nodal involvement, tumor grade and size, local invasion at operation, invasion of contiguous structures at histology, and postoperative complications.
More patients in the placebo group had radiation-induced diarrhea compared with the VSL#3 group (52 of 95 and 36 of 95, respectively, p < 0.001), and patients treated with placebo also had more severe disease compared with VSL#3 recipients. Grade 3 or 4 diarrhea was documented in 28 of 95 placebo-treated patients and seven of 95 VSL#3-treated patients (p < 0.001), whereas 20 of 95 of placebo-treated patients had grade 1 or 2 diarrhea compared with 29 of 95 VSL#3 recipients (ns). The mean daily number of bowel movements for patients with radiation-induced diarrhea was 12.3 - 4 and 4.6 - 2 among placebo and VSL#3 recipients, respectively (p < 0.05), and the mean time to the use of loperamide as rescue medication for diarrhea was 97 - 4 h for patients receiving placebo versus 118 - 6 h for patients receiving VSL#3 (p  0.001). Two patients in the placebo group had to discontinue treatment because of gastrointestinal toxicity, and none of the VSL#3 recipients discontinued treatment for this reason. No tumor- or treatment-related deaths or deaths from other causes were recorded in either group during the study period, and no treatment-related toxicity was reported among the VSL#3 recipients.
Gastrointestinal tract damage by radiation limits the efficacy of abdominal radiotherapy in cancer treatment. The results of our pilot clinical study indicate that bacterio-therapy with the use of probiotic lactobacilli may protect patients against the risk of radiation-induced diarrhea. This could have an additional clinical fallout as fewer patients treated with probiotic lactobacilli should be expected to discontinue radiotherapy or require a reduction in the radiation dose because of severe gastrointestinal toxicity. This might ultimately allow patients treated with probiotic lactobacilli to receive a greater cumulative radiation tumor dose with a potentially important benefit in terms of efficacy of radiotherapy. We have not specifically addressed this issue in our study; however, no subject in the VSL#3 group discontinued radiotherapy because of gastrointestinal toxicity
as compared with two patients in the placebo group. This finding appears to be in line with the above hypothesis.
Although a recent study has reported favorable results with Lactobacillus GG bacteriotherapy for radiation-in-duced colitis (3), we designed to use VSL#3 rather than Lactobacillus GG or other traditional preparations of pro-biotic lactobacilli for several reasons.

The clinical potential of VSL#3 in the treatment of inflammatory bowel disease has been validated by several studies (4, 5), whereas reports of Lactobacillus GG have been somewhat conflicting (6, 7).
VSL#3 is a high-potency preparation with innovative characteristics compared with traditional probiotics, in particular the enormously high bacterial concentration and the presence of a consortium of different bacterial species with potential synergistic relations between different strains enhance suppression of potential pathogens (2). The composite
mixture of this preparation with a large number of probiotic strains possessing very different and specialized metabolic and immunoregulatory activities is a unique feature of
VSL#3, and may explain its wide spectrum of biological activities (2). This is most important as the different species of probiotic lactobacilli may exert very different biological and immunomodulatory effects (8), and the health benefits ultimately resulting from probiotic bacteriotherapy strictly depend upon the metabolic and biologic diversity of the ingested lactobacilli (2, 9). In this view, the widely different biological, immunoregulatory, and metabolic characteristics contained within the probiotic lactobacilli and bifidobacteria of VSL#3 greatly enhance its therapeutic potential, compared
with traditional probiotic preparations.
We have not analyzed the bacterial content of stool samples from patients treated with VSL#3. However, previous experience with this probiotic preparation has shown that
colonization of intestinal niches with protective lactobacilli and bifidobacteria and reconditioning of the endogenous digestive microflora occurs in almost all the subjects treated with VSL#3 (4, 5).
In vitro experiments with VSL#3 have demonstrated the ability of the bacterial strains contained in this probiotic preparation to regulate the process of apoptosis (10, 11). This
property of VSL#3 may be crucial for explaining the protective effect against radiation-induced colitis in patients treated with radiotherapy. Recent studies in experimental models have indeed demonstrated that an unregulated process of apoptosis is
the primary mechanism of radiation-induced intestinal damage
(12). Furthermore, VSL#3 lowers the production of proinflammatory cytokines and several other effectors of inflammation and tissue injury, such as nitric oxide and metalloproteinases (13). Taken together, these mechanisms ultimately account for the significant protection exerted by VSL#3 upon the integrity of the gastrointestinal intestinal epithelial barrier (14). Although we have not a direct proof, it is conceivable that VSL#3 is operating through these same mechanisms in patients at risk for radiation-induced colitis.
In our study, none among the patients given VSL#3 experienced treatment-related toxicity. Previous clinical experience with this probiotic preparation has indeed demonstrated
the remarkable safety of VSL#3 bacteriotherapy even with dosages significantly greater than those we used in this trial. Therefore, it is our opinion that VSL#3 is a safe treatment even for cancer patients receiving radiotherapy. Our preliminary observation, of course, needs to be independently confirmed in a larger number of patients. However, our data suggest that treatment with probiotic bacteriotherapy has the potential to protect the gastrointestinaltract against radiation injury. Furthermore, this study indirectly
lends support to the view that the severe and potentially lethal gastrointestinal syndrome caused by abdominal radiotherapy is related to a quantitative and/or qualitative alteration in the microecology of resident intestinal bacteria.
If confirmed, the results of this study could pave the way to pre-emptive treatment with probiotic preparations for subjects at risk for radiation-induced diarrhea to reduce both the incidence and severity of this complication.
We thank Prof. Fabio Cominelli for the helpful criticism of the manuscript.
Pietro Delia, M.D.
Giuseppe Sansotta, M.D.
Valentino Donato, M.D.
Giovanna Messina, M.D.
Pasquale Frosina, M.D.
Stefano Pergolizzi, M.D.
Costantino De Renzis, M.D.
Institute of Radiology
Oncologic Radiotherapy Unit
Azienda Ospedaliera Universitaria
Messina, Italy
Giuseppe Famularo, M.D., Ph.D.
Department of Internal Medicine
San Camillo Hospital
Rome, Italy
1. Donner CS. Pathophysiology and therapy of chronic radiation-induced injury to the colon. Dig Dis 1998;16:253–61.
2. Famularo G, De Simone C, Matteuzzi D, Pirovano F. Traditional and high-potency probiotic preparations: Advances, perspectives and safety of oral bacteriotherapy. Biodrugs 1999;
3. Urbancsek H, Kazar T, Mezes I, Neumann K. Results of a double-blind, randomized study to evaluate the efficacy and safety of Antibiophilus in patients with radiation-induced diarrhoea. Eur J Gastroenterol Hepatol 2001;13:391–5.
4. Venturi A, Gionchetti P, Rizzello F, et al. Impact on the composition of the faecal flora by a new probiotic preparation: Preliminary data on maintenance treatment of patients with
ulcerative colitis. Aliment Pharmacol Ther 1999;13:1103–8.
5. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: A double-blind, placebo-controlled trial. Gastroenterology 2000; 119:305–9.
6. Malin M, Suomalainen H, Saxelin M, et al. Promotion of IgA immune response in patients with Crohn’s disease by oral bacteriotherapy with Lactobacillus GG. Ann Nutr Metab
7. Prantera C, Scribano ML, Falasco G, et al. Inefficacy of probiotic in preventing recurrence after curative resection for Crohn’s disease: A randomised controlled trial with Lactobacillus GG. Gut (in press).
8. Christensen HR, Frokiaer H, Pestka JJ. Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J Immunol 2002;168:171-8.
9. Campieri M, Gionchetti P. Probiotics in inflammatory bowel disease: New insight to pathogenesis or a possible therapeutic alternative? Gastroenterology 1999;116:1246 -9.
10. Di Marzio L, Russo FP, D’Alo` S, et al. Apoptotic effects of selected strains of lactic acid bacteria on human T leukemia cell line are associated with bacterial arginine deiminase
and/or sphingomyelinase activities. Nutr Cancer 2001;40:185-96.
11. Di Marzio L, Cinque B, De Simone C, Cifone MG. Effect of the lactic acid bacterium Streptococcus thermophilus on ceramide levels in human keratinocytes in vitro and stratum
corneum in vivo. J Invest Dermatol 1999;113:98 -106.
12. Paris F, Fuks Z, Kang A, et al. Endothelial apoptosis as the primary lesion initiating intestinal radiation damage in mice. Science 2001;293:293–7.
13. Ulisse S, Gionchetti P, D’Alo` S, et al. Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis: Effect of probiotic treatment. Am J Gastroenterol 2001;96:2691-9.
14. Madsen K, Cornish A, Soper P, et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 2001;121:580 -91. Reprint requests and correspondence: Giuseppe Famularo, M.D., Ph.D., Department of Internal Medicine, Ospedale San Ca-millo, Circonvallazione Gianicolense, 00152, Rome, Italy.
Received Mar. 7, 2002; accepted Mar. 14, 2002.

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