Systematic Review: Are Probiotics Useful in Controlling Gastric Colonization by Helicobacter pylori?

M. Gotteland; O. Brunser; S. Cruchet


Aliment Pharmacol Ther. 2006;23(8):1077-1086. 

In This Article

Inhibition of H. Pyloriby Organic Acid and Bacteriocin-Producing Probiotics

Two main types of substances have been implicated in the inhibition of H. pylori by lactic acid bacteria: short chain fatty acids (SCFAs) and bacteriocins. SCFAs such as formic, acetic, propionic, butyric and lactic acids are produced during the metabolism of carbohydrates by probiotics and have an important role in decreasing pH. Bhatia et al. were the first to observe an antagonistic effect of a Lactobacillus strain against H. pylori[20] and to implicate SCFAs in this effect. A dose-dependent inhibition of H. pylori growth has been observed with acetic and lactic acid, the later demonstrating the most intense effect.[21] The amounts of lactic acid released by strains of Lactobacillus, Bifidobacterium and Pediococcus (50--156 mΜ) correlated with the intensity of their inhibitory effect against H. pylori. Such antimicrobial activity could be due not only to a direct effect on Helicobacter but also to the inhibition of its urease activity, as shown with the high lactic acid producers L. salivarius and L. casei Shirota.[22,23] Interestingly these strains, when administered to colonized mice, induced a significant decrease in the counts of H. pylori in the body and antral mucosa compared with untreated animals, and resulted in a concomitant reduction in the associated gastric inflammation. A traditional yogurt originating from Asia was recently evaluated for its bactericidal activity against H. pylori;[24] both the yeasts (Kluyveromyces lactis and Issatchenkia orientalis) and lactobacilli (L. crispatus and L. kefiri) present in the product exert independently an anti-H. pylori activity. This yogurt had high levels of lactic acid and formic acid but only the latter was found to have a consistent inhibitory effect against H. pylori.

Bacteriocins are compounds with potential anti-H. pylori activity. They are small, heat-resistant and dialysable peptidic structures with antimicrobial activities, which are synthesized by several bacterial species including lactic acid bacteria. Many bacteriocins have been characterized and some of them, such as nisin, are added to foodstuffs to decrease the risk of contamination by pathogens.

The release of bacteriocins with anti-H. pylori activity has been chiefly studied in Lactobacillus, but probiotic strains of Enterococcus faecium,[25]Bacillus subtilis[26] and Bifidobacterium[27] could also produce heat-stable proteinaceous compounds capable of inhibiting the growth of both antibiotic-resistant and -sensitive strains of H. pylori. Kim et al.[28] evaluated, by microdilution assay, the anti-H. pylori activity of seven bacteriocins produced by lactic acid bacteria, including nisin A, pediocin PO2, leucocin K and various types of lacticins. Lacticins A164 and BH5 produced by strains of L. lactis had the most potent activity, with minimum inhibitory concentrations varying from 0.097--0.390 mg/L to 12.5--25 mg/L depending on the strains of H. pylori tested, indicating a strain-dependent sensitivity of this pathogen. In a co-culture experiment, Lorca et al. showed that after 24 h of culture an autolysate of L. acidophilus CRL 639 induced the release of a proteinaceous compound and the subsequent mortality of all H. pylori after 48 h.[29]

The supernatant of a culture of the probiotic strain, L. johnsonii La1 was shown to inhibit both the urease activity and growth of H. pylori.[30] This inhibitory activity remained functional even when H. pylori was bound to HT-29 epithelial cells; furthermore, this activity was not observed with La10, another strain of L. johnsonii, indicating that it is strain-specific, and was independent of the presence of the cag pathogenicty island in H. pylori strains. The supernatant inhibitory activity was heat resistant, dialysable and not affected by 10 mΜ urea, being therefore compatible with the presence of a bacteriocin. Although the molecule responsible for this effect was not purified and characterized by the authors, it could be lactacin F, a two-component class II bacteriocin produced by L. johnsonii and composed of LafA and LafX peptides which may combine to form a pore in the membrane of sensitive bacteria, resulting in the efflux of intracellular ions and the eventual death of the pathogen in this case.[31] As discussed later, the administration of this supernatant to adult patients colonized by H. pylori significantly decreased the values of 13C-urea breath test (13C-UBT).

Similar findings were observed by Coconnier et al. incubating H. pylori with the culture supernatant of L. acidophilus LB; the viability of the pathogen as well as its urease activity and its binding to the HT29-MTX cell line decreased in a dose-dependent manner.[32] This effect was independent of the presence of lactic acid and the pH and was not suppressed by heating at 100 °C for 1 h, supporting the presence of at least one bacteriocin. Interestingly, H. pylori was morphologically affected by the incubation with supernatant of the LB culture, changing from its characteristic curved form with polar flagella to U-shaped and decreased size, considered as pre-coccoid. No effects on H. pylori were observed by these authors using the culture supernatant of another well-known probiotic strain, L. rhamnosus GG (LGG). On the other hand, oral treatment of conventional mice with a supernatant of Lactobacillus LB culture protected the animals from infection with H. felis by decreasing its urease activity, inhibiting gastric colonization and preventing the development of gastric inflammation.