Manfred Lamprecht, PhD, PhD
Adj. Professor
Centre for Physiological Medicine
Medical University of Graz
Harrachgasse 21/II
8010 Graz, AUSTRIA
+436641555528 / +433163809610 (FAX)
manfred.lamprecht@medunigraz.at / www.medunigraz.at
“Probiotic Supplementation Affects Markers of Intestinal Barrier, Oxidation, and Inflammation in Trained Men; A Randomized, Double-Blinded, Placebo-Controlled Trial,” J Int Soc Sports Nutr, 2012 Sep 20; 9(1):45. 49368 (11/2012)
Kirk Hamilton: Can you please share with us your educational background and current position?
Manfred Lamprecht: I have a PhD in Sport and Movement Sciences and PhD in Medical Sciences. I am currently the Director of Green Beat – Institute of Nutrient Research and Sport Nutrition, Graz, Austria. As researcher and teacher I´m also affiliated with the Institute of Physiological Chemistry, Center for Physiological Medicine, Medical University of Graz, Graz, Austria.
KH: What got you interested in studying the role of probiotics on intestinal permeability in trained athletes (triathletes, runners, cyclists)?
ML: Our practical work reveals that many endurance athletes report gastrointestinal complaints, bloating, intestinal cramps, diarrhea etc. We hypothesize that the reduced intestinal barrier function is involved in these outcomes. Several clinical studies with patients of e.g. IBS or Morbus Crohn report that probiotics could improve intestinal barrier integrity. Why not in athletes as well?
KH: What is the biochemistry of a probiotic that might alter the pathophysiology of gut permeability?
ML: Several Bifidobacteria or Lactobacteria might communicate directly – or their metabolites – with certain receptors, e.g. TLR2 and TLR4 on epithelial cells in the gut wall. This communication leads to increased expression of tight junction proteins by the cell which in turn promotes rebuilding of tight junctions and intestinal barrier integrity.
KH: Where did you come up with a probiotic supplement with a minimum concentration of 2.5 × 109 colony forming units (CFU) per gram, at a dose of 2 sachets per day at 2 g each (4 g/day), equivalent to1010 CFU/day taken in 100–125 mL of plain water with one sachet taken one hour prior to meals for 14 weeks?
ML: Current evidence shows that 1010 CFU/day is an appropriate dosage to be effective. Water is important to rehydrate the bacteria that activates them before intake. Intake away from meals is more effective because food intake increases the production of acids which in turn reduces bacteria efficacy.
KH: Why did you choose the six strains of probiotics that you did: Bifidobacterium bifidum W23, Bifidobacterium lactis W51, Enterococcus faecium W54, Lactobacillus acidophilus W22, Lactobacillus brevis W63, and Lactococcus lactis W58?
ML: Pre-investigations in vitro and ex-vivo showed better efficacy regarding anti-inflammatory and antioxidant actions when we used multi-strain prototypes. The mentioned combination was the most effective.
KH: Were blood or stool levels of inflammatory or other biochemical markers taken before, during or after the intervention? If so did they correlate with symptoms and supplementation with the probiotic?
ML: We measured carbonyl proteins (CP) and malondialdehyde (MDA) as well as TNF-alpha and IL-6 from serum pre- and post exercise. CP, as a marker of protein oxidation, was reduced with probiotics, pre and post exercise. The same goes to TNF-alpha, a low-grade inflammation marker which is also associated with a “leaky gut”. IL-6 was increased post exercise, indicating that these were intense exercise bouts. MDA, as a marker of lipid peroxidation, did not change, neither with supplementation nor with exercise. At rest, these trained men usually have no or less GI complaints, but under longer lasting exercise conditions they often suffer with problems. They reported that the probiotic treatment did reduce these symptoms. As our N was too small (N=23) these observations and comments were not reported in the paper.
KH: Can you tell us about your study and the basic results?
ML: In a randomized, double-blinded, placebo controlled trial twenty-three trained men received multi-species probiotics (1010 CFU/day, Ecologic®Performance or OMNi-BiOTiC®POWER, n = 11) or placebo (n = 12) for 14 weeks and performed an intense cycle ergometry over 90 minutes at baseline and after 14 weeks. The most important result was the reduction of zonulin in the stool, a marker of gut barrier integrity. Zonulin was slightly increased at the beginning of the study, indicating already a mild leaky gut problem due to chronic and intense exercise training or lack of recovery. However, after 14 weeks with multi-species probiotics zonulin was decrease by about 20% into a physiological range below cut off. For the rest, please see answer to the question before.
KH: A definition from Wikipedia of zonulin is “a protein that modulates the permeability of tight junctions between cells of the wall of the digestive tract…it has been implicated in the pathogenesis of coeliac disease and diabetes mellitus type 1…Gliadin (glycoprotein present in wheat) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.” Is this a reasonable definition? Where exactly does zonulin come from? Are there nutraceuticals that lower zonulin? Dietary factors that increase its secretion?
ML: Your description on zonulin is absolutely correct. Zonulin is a protein that acts as an enterotoxin and it is allocated to the haptoglobin family. It is released from liver and intestinal epithelial cells after a stimulus
e.g. via gliadin or metabolites of gram-negative bacteria. Hypothetically, also other nutrients and nutraceuticals – besides probiotics – may affect zonulin concentrations, e.g. tea and black, green or sweet pepper, or their extracts. Also amino acids or proteins like arginine, alanine or casein interact with the intestinal barrier. However, I don´t know studies which investigated the influence of these food components on zonulin concentrations directly.
KH: Regarding those nutrients and foods you just mentioned above since they are commonly consumed; Can you just list if they INCREASE or DECREASE intestinal permeability? In other words are they
beneficial to improving gut permeability or do they aggravate gut permeability?
ML: There are several studies which investigated the transepithelial electrical resistance (TEER) – an in vitro test model to evaluate permeability of polarized cell monolayers – in response to plant extracts. These studies revealed that sweet pepper extract, cayenne pepper, paprika, or w-3s like DHA and EPA caused a decrease in TEER. In opposite, black and green pepper, black tea extract, arginine, glutamine or quercetin increased TEER, this would be beneficial. But such results do not allow to draw conclusions or recommendations to avoid or prefer certain food components. With whole food intake in vivo we have a new situation.
KH: Were there any side effects with this probiotic therapy? How was the patient compliance?
ML: No, there were no side-effects reported. Compliance was >90%.
KH: Who is a candidate for probiotic therapy? Elite athletes? Do they have an increase in intestinal permeability? Those with chronic inflammatory bowel disease? Immune compromised patients? Critically
ill patients? Who is this therapy for?
ML: Top endurance athletes should undergo a screening to check intestinal barrier integrity as they are susceptible to suffer from disturbed gut wall function. The same goes to patients with chronic inflammatory bowel disease. Athletes with more than 3 common colds a year or allergies are also candidates to undergo a screening. The problem might ‘slumber’ in the gut wall. For critically ill patients I´m not competent enough to answer. For basically healthy and sporty people, duration of intake should last at least 3 months.
KH: When you say “screening” you are referring to checking zonulin levels? Zonulin was accessed in the stool in this study. Can you assess zonulin levels from the serum? What is the best way for the busy clinician
test for intestinal permeability?
ML: Yes, you can measure zonulin from serum but we believe that this is less meaningful than from stool. We believe that stool zonulin determination is one of the most appropriate and easiest ways to estimate
intestinal permeability. We used a commercially available ELISA which performed well.
KH: How can the public or health professionals use this information?
ML: See answer to the question above.
KH: Do you have any further comments on this very interesting subject?
ML: There is a lot of work to do: to identify the exact mechanisms of action of zonulin on tight junction integrity; to identify the mechanism of tight junction rebuilding; which strains or nutrients perform best to
support this; don´t forget the matrix (prebiotics) which feeds the probiotics etc. A follow up study in regard of exercise-induced intestinal barrier dysfunction is already planned.
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