Scientific Opinion on the substantiation of health claims related to a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722 and defence against pathogenic gastro-intestinal microorganisms (ID 939, further assessment) pursuant to Article 13(1) of
Regulation (EC) No 1924/2006[sup]1[/sup]
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3
European Food Safety Authority (EFSA), Parma, Italy
ABSTRACT
Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a health claim related to a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722 and defence against pathogenic gastro-intestinal microorganisms. The food constituent that is the subject of the health claim, a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722, is sufficiently characterised. The claimed effect, defence against pathogenic gastro-intestinal microorganisms, is a beneficial physiological effect. The proposed target population is the general population. No human intervention studies were provided from which conclusions could be drawn for the scientific substantiation of the claim. On the basis of the data provided, the Panel concludes that a cause and effect relationship has not been established between the consumption of a combination of Lactobacillus rhamnosus CNCM I-1720 and Lactobacillus helveticus CNCM I-1722 and defence against pathogenic gastro-intestinal microorganisms.
© European Food Safety Authority, 2012
Słowa kluczowe:
CNCM I-1720
CNCM I-1722
Lactobacillus helveticus
Lactobacillus rhamnosus
gastro-intestinal pathogens
health claims
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claims is a combination of Lactobacillus rhamnosus CNCM I-1720 (hereafter L. rhamnosus CNCM I-1720) and Lactobacillus helveticus CNCM I-1722 (hereafter L. helveticus CNCM I-1722).
The strain L. rhamnosus CNCM I-1720 is also known as L. rhamnosus R0011. A culture collection number from the Collection Nationale de Cultures de Microorganismes (CNCM), I-1720, was provided. The CNCM is a restricted-access non-public collection, which has the status of an International Depositary Authority under the Budapest Treaty. Data on the identification and characterisation of L. rhamnosus CNCM I-1720 at species and strain level using both phenotypic (cell morphology, colony morphology, carbohydrate fermentation pattern and enzymatic activity profile) and genotypic (DNA-DNA hybridisation, 16S rRNA gene sequence analysis, 16S/23S intergenic spacer region sequence analysis, RAPD and PFGE) methods were provided in the application and accompanying references (Provencher et al., 2003; Roy and Ward, 2004; Yeung et al., 2002) .
The strain L. helveticus CNCM I-1722 is also known as L. helveticus R0052. A culture collection number from the CNCM, I-1722, was provided. Data on the identification and characterisation of L. helveticus CNCM I-1722 at species and strain level using both phenotypic (cell morphology, colony morphology, carbohydrate fermentation pattern, enzymatic activity profile, antimicrobials resistance pattern and PAGE) and genotypic (DNA-DNA hybridisation, 16S rRNA gene sequence analysis, 16S/23S intergenic spacer region sequence analysis, species-specific PCR, AFLP, MLST, RAPD and PFGE) methods were provided in the application and accompanying references (Naser et al., 2006; Yeung et al., 2002).
The formulation which is the subject of the claim is a combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 in a 95:5 ratio.
The Panel considers that the food constituent, a combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722, which is the subject of the health claim, is sufficiently characterised.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka - Obrona przed patogenami przewodu pokarmowego
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Obrona przed patogenami przewodu pokarmowego
Of the references provided in relation to the claim, nine were human studies (five studies were on antibiotic-associated diarrhoea, two related to Helicobacter pylori (hereafter H. pylori) eradication therapy, and two on the treatment of diarrhoea), eight were animal studies, and six were in vitro studies. Five papers were published in Ukrainian and one in Czech, and their full English translations were given.
All the studies were carried out with the combination of microorganisms that is the subject of the health claim, consisting of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 in a 95:5 ratio.
Studies on antibiotic-associated diarrhoea (AAD)
One study in adults and four studies in children which investigated the effect of the combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 on AAD were provided.
Two studies were conducted in Korean hospitalised adult patients and in Ukrainian children with cystic fibrosis, respectively, under antibiotic treatment for respiratory tract infections (Aryayev and Kononenko, 2009; Song et al., 2010). The Panel notes that the infectious nature of the diarrhoeal episodes was not clearly established by the diagnostic criteria used, that causes of diarrhoea other than GI infections were not systematically excluded, that microbiological analyses were not performed, and that antibiotic treatment may induce diarrhoea by mechanisms unrelated to GI infections. The Panel considers that no conclusions can be drawn from these studies for the scientific substantiation of a claim related to defence against pathogenic gastro-intestinal microorganisms.
In a randomised, open-label study, Marushko and Shef (2007) evaluated the effect of the combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 added to antibiotic therapy vs. antibiotic therapy alone (control) in a group of 34 hospitalised children with pneumonia or bronchitis aged from 10 months to 3 years. The presence and duration of diarrhoea, abdominal pain, abdominal bloating and vomiting were measured, and microbiological analyses of stools before and after treatment were performed. The Panel notes that the methodology used for the microbiological analyses was not well described, that the bacterial groups analysed were not sufficiently characterised as pathogens, and that the evidence provided, therefore, did not establish the infectious aetiology of the episodes of diarrhoea. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of a claim related to defence against pathogenic gastro-intestinal microorganisms.
Maydannik et al. (2010), in a multicentre, randomised, open-label study, assessed the effect of the combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 together with antibiotic therapy vs. antibiotic therapy alone (control) on the incidence and duration of diarrhoea, and on the presence of C. difficile toxins A and B in 244 children with infections of the respiratory, urinary or digestive tracts, and who received antibiotic therapy for not less than seven days. The Panel notes that
no information was provided about the baseline characteristics of the two study groups (e.g. age and carrier status for С. difficile toxins), that precise information on type and duration of the antibiotic treatment in the two study groups was not provided even though development of AAD was reported to be influenced by the type of antibiotic used, and that the statistical tests used in the data analyses were not described. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim.
In an open-label study, Gnaytenco et al. (2009) compared the incidence of AAD related to standard triple H. pylori eradication therapy (control; omeprazole, amoxicillin and clarithromycin for seven days) with the same therapeutic regimen taken together with the combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 in 45 subjects. The incidence of diarrhoea was measured and the assessment for C. difficile toxins A and B was performed at the beginning and at the end of the intervention. The Panel notes that it is unclear whether the study was randomised, that no information was provided on the baseline characteristics of the two study groups (e.g. clinical features, age and carrier status for С. difficile toxins), and that the statistical tests used in the data analyses were not described. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim.
Studies on H. pylori eradication
Two open-label trials conducted in subjects with H. pylori infection undergoing treatment with antibiotics and proton pump inhibitor therapy for H. pylori eradication assessed the effect of the combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 as co-adjuvant therapy for H. pylori eradication (Vdovychenkon et al., 2008; Ziemniak, 2006). The Panel notes that no evidence was provided that results obtained in patients with H. pylori infection under antibiotics with respect to treatment of the disease can be extrapolated to healthy subjects with respect to the development of H. pylori infection. The Panel considers that no conclusions can be drawn from these studies for the scientific substantiation of a claim on defence against pathogenic gastro-intestinal microorganisms targeted to the general population (i.e. subjects without infections).
Treatment of diarrhoea
Two studies addressed the use of the combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 for the treatment of acute and chronic diarrhoea of various origins, including GI infections, in hospitalised children (Tlaskal et al., 1995; 2005). The Panel notes that the status of the GI tract in subjects with diarrhoea due to a GI infection may not be comparable to the status of the GI tract in subjects without GI infection. The Panel considers that no conclusions can be drawn from these studies for the scientific substantiation of the claim.
Animal and in vitro studies
The animal studies provided evaluated the effect of the combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 on the treatment of experimental Citrobacter rodentrium infection in adult mice (Johnson-Henry et al., 2005) and neonatal mice (Gareau et al., 2010), on bacterial translocation from the intestine to the lymph nodes and on the intestinal barrier function in rats experiencing chronic psychological stress (Zareie et al., 2006), on mucin expression in a rat model (Dykstra et al., 2011), on colonic macromolecular permeability and corticosterone level in an animal model of stress induced by neonatal maternal separation (Gareau et al., 2007), on the rate of H. pylori eradication in Mongolian gerbils (Brzozowski et al., 2006), on H. pylori colonisation in mice (Johnson-Henry et al., 2004), and on GI functions and immune markers (e.g. gastric emptying, intestinal permeability and gastric CD3+ cell counts) after chronic H. pylori infection in mice (Verdu et al., 2008).
The in vitro studies submitted investigated the effects of a combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 on the interaction of Camplylobacter jejuni with a cell line or
invasion of T48 epithelial cell line (Alemka et al., 2010; Wine et al., 2009), on cytokine secretion by a human intestinal epithelial cell line (Wallace et al., 2003), on epithelial injury (paracellular permeability) following exposure to Escherichia coli O157:H7 (Sherman et al., 2005), on adhesion of Escherichia coli O157:H7 to epithelial cells (Johnson-Henry et al., 2007), and on the immune effects of Escherichia coli O157:H7 infection in epithelial cells (Jandu et al., 2009).
The Panel notes that no human intervention studies were provided from which conclusions could be drawn for the scientific substantiation of the claim. The Panel also notes that animal and in vitro studies cannot predict the occurrence of an effect of a combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 on defence against pathogenic gastro-intestinal microorganisms in humans.
The Panel concludes that a cause and effect relationship has not been established between the consumption of a combination of L. rhamnosus CNCM I-1720 and L. helveticus CNCM I-1722 and defence against pathogenic gastro-intestinal microorganisms.
