Systematic review: are probiotics useful in controlling gastric colonization by Helicobacter pylori?
Dr M. Gotteland, Laboratory of Microbiology, INTA, University of Chile, J.P. Alessandri 5540, Macul, Santiago, Chile.
Helicobacter pylori is a highly prevalent pathogen considered as an aetiological factor for gastroduodenal ulcers, and a risk factor for gastric adenocarcinoma and lymphoma in humans. Most subjects colonized by this micro-organism are asymptomatic and remain untreated. In symptomatic patients, the antibiotic treatment has a high cost and is not 100% effective because of resistance to antibiotics and to moderate patient compliance. This review discusses the role of probiotics as alternative solutions to assist in the control of H. pylori colonization in at-risk populations.
The evidence that some strains of Lactobacillus and Bifidobacterium are able to inhibit H. pylori growth through the release of bacteriocins or organic acids, and may also decrease its adhesion to epithelial cells, is reviewed. In addition, probiotics have a possible role in the stabilization of the gastric barrier function and the decrease of mucosal inflammation. Other aspects that are considered are the contribution of probiotics to the healing of the gastric mucosa linked to their antioxidant and anti-inflammatory properties.
Clinical trials in colonized adults and children are reviewed, and suggest that probiotics do not eradicate H. pylori but maintain lower levels of this pathogen in the stomach; in combination with antibiotics, probiotics may increase eradication rate and/or decrease adverse effects. Papers suggesting similar effects on H. pylori by foodstuffs such as berry juice and some milk proteins are quoted. Regular intake of these and other dietary products might constitute a low-cost, large-scale alternative solution applicable for populations at-risk for H. pylori colonization.
H. pylori: an important factor for gastroduodenal pathologies
Helicobacter pylori is a micro-organism that colonizes specifically the surface of the mucosa of the stomach; its role as a gastric pathogen was first described by Marshall and Warren, 22 years ago,1 in studies that earned the 2005 Nobel Prize for Physiology and Medicine. It is a Gram-negative, microaerophilic, fastidious bacterium that, in the process of colonization, induces a chronic inflammation of the mucosa without invading it. All infectious strains of H. pylori release large amounts of a urease that, through the degradation of urea to ammonia, is capable of buffering the gastric acid in their microenvironment. The mode of transmission of H. pylori remains incompletely understood but must be very efficient: in the less developed countries, the pathogen is generally acquired during childhood and, if untreated, the infection will persist throughout the life of the individual.2, 3Helicobacter pylori is one of the most prevalent pathogens as more than 50% of the world population is colonized by this micro-organism, low socio-economic level and bad hygienic conditions being the main risk factors. In consequence, the prevalence of infection is lower and begins later in developed countries where 30–40% of the population is infected in adulthood while in developing countries this rate reaches 80–90% in adulthood and most children are already colonized by 10 years of age.2–5 Gastric colonization by H. pylori results in a chronic gastritis which will remain asymptomatic in most subjects who, consequently, may not be treated with antibiotics to eradicate it.
Gastroduodenal symptoms and pathologies develop in 10–15% of the infected population, with H. pylori being recognized as one of the aetiological agents of peptic ulcer and a risk factor for the development of gastric adenocarcinoma and lymphoma.2–4 The determinants for severe disease outcomes include the host's genetic background, specific virulence factors present in some strains such as the cag pathogenicity island and environmental and dietary factors.2, 6, 7 The treatment currently available for colonized symptomatic patients includes a combination of antibiotics (amoxicillin, clarythromicin, metronidazol, etc.) and a proton-pump inhibitor (omeprazol, lanzoprazol, pentoprazol, etc.) for 1–2 weeks.2 However, this treatment does not eradicate H. pylori in all patients because of the appearance of antibiotic resistance and moderate patient compliance due to adverse effects such as vomiting, diarrhoea, abdominal pain and taste alterations. The high cost of the treatment, in particular for families from the low socio-economic stratum, where H. pylori is more frequent, also limits its adequate application. In addition, children who need to be treated tend to relapse more frequently and rapidly than adults. Therefore, it is important to develop low-cost, large-scale, alternative solutions applicable to the at-risk population to prevent or decrease H. pylori colonization.
The aim of the present review was to summarize the published studies using probiotics and other functional foodstuffs as possible gastroprotective agents to control H. pylori growth and to decrease gastric inflammation. The search strategy in Medline used the following keywords: Helicobacter pylori, probiotics, Lactobacillus, Bifidobacterium, Saccharomyces boulardii, bacteriocin, berries, functional foods, gastric ulcer and gastritis.
The normal gastric microbiota as a possible protective factor for the gastric mucosa
Lactobacillus species are commensal in the human alimentary tract and their concentrations in the normal stomach vary between 0 and 103/mL. Being acid resistant, they persist in the stomach longer than other bacteria: dietary strains of bifidobacteria and lactobacilli survive in high proportions (>80%) in the gastric environment for periods of 2 h.8 Furthermore, some strains of Lactobacillus adhere to gastric epithelial cells in vitro9 and also to the keratinized squamous epithelium of the mouse forestomach, probably through lipoteichoic acid.10 This has been recently confirmed by Valeur et al. who reported that, after administration of 4 × 108L. reuteri ATCC 55730 to healthy volunteers, it was possible to detect this strain adhering to epithelial cells from corpus and antral gastric biopsies using fluorescent in situ hybridization.11
The possible role of the local microbiota in the protection against gastric lesions is suggested by the study of Elliott et al.12 in which the authors observed that the level of total aerobes in the stomach of healthy rats ranged from 103 to 104 CFU/g of tissue, with Gram-negative micro-organisms representing only 5% of the population; autochthonous gastric lactobacilli were present in all rats. However, 1 day after the induction of gastric ulcers through the serosal application of acetic acid the total aerobe count peaked at 109–1010/g and remained high for 1 week. At this time, Gram-negative bacteria including Escherichia coli represented the majority of the total aerobes while the Lactobacillus population disappeared. Colonization by Gram-negative bacteria occurred preferentially at the site of ulcer where a more alkaline pH (>5) was observed. The authors observed smaller ulcers in animals treated with antibiotics, suggesting that the alteration of homeostasis of the resident microbiota contributed to the development and persistence of the lesion. The ulcer healed simultaneously with the normalization of the microbiota including the reappearance of a dominant Lactobacillus population, and these processes were accelerated by the oral administration of lactulose, a non-digestible disaccharide used as substrate by the Lactobacillus population.
These findings suggest that the gastroduodenal microbiota, though low numerically, could participate in the protection of the mucosa. In consequence, the intake of exogenous lactic acid bacteria, particularly those with probiotic properties, may reinforce these protective functions in the stomach by maintaining local microbiological homeostasis, interfering with H. pylori and/or decreasing inflammatory processes.13
Probiotics are generally recognized as safe micro-organisms; they are mostly lactic acid bacteria such as lactobacilli and bifidobacteria, which are present in high concentrations in some foodstuffs; in addition, yeasts such as Saccharomyces boulardii are also considered as probiotics. Probiotic micro-organisms survive during their transit along the gastrointestinal tract where they modulate the gut microbiota and exert health-promoting activities beneficial for the host. The most important properties of probiotics are related to the regulation of intestinal microbiota homeostasis, interference with pathogens, modulation of local and systemic immune responses, stabilization of the gastrointestinal barrier function, decrease of procarcinogenic enzymatic activities and production of enzymatic activities of nutritional interest.14–19 Various in vitro studies support the use of probiotics with the aim of interfering H. pylori colonization.
Inhibition of H. pylori by 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. pylori20 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 mm) 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,25Bacillus subtilis26 and Bifidobacterium27 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 mm 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.
Anti-inflammatory properties of probiotic strains
As described previously, L. acidophilus LB and L. johnsonii La1 decrease gastric inflammation in colonized animals.30, 32 This was also observed with other probiotic strains: L. salivarius WB1004 (108 CFU/mL) was able to displace H. pylori adhering to the MKN45 cell line and to exert an anti-inflammatory effect by decreasing dose dependently the release by these cells of IL-8.33 Therefore, this same probiotic strain was used to evaluate its preventive effect in gnotobiotic BALB/c mice mono-colonized by H. pylori. Administration of L. salivarius prevented H. pylori colonization and the development of gastritis; this effect was specific of this probiotic as it was not observed with other micro-organisms such as E. faecalis and S. aureus. Administration of L. salivarius after infection eradicated H. pylori and reversed gastric inflammation. Similar observations were reported with L. rhamnosus R0011 and L. acidophilus R005234 and with L. gasseri OLL2716.35 Furthermore, the intake of yogurt containing this latter strain protected rats in a dose-dependent manner against acute gastric lesions induced by oral administration of HCl, compared with the administration of non-fermented milk.36 The size of the gastric lesions was decreased by yogurt and this was associated with significantly increased levels of PGE2 in the gastric mucosa. Such protective activity was inhibited when indomethacin was injected, confirming the importance of prostaglandins in this effect.
Increased levels of 6-ketoprostaglandin F1-α, EGF and bFGF have also been implicated in the protective effect displayed by strains of B. breve and B. bifidum against gastric ulceration induced by acetic acid or ethanol in rats.37 Interestingly, the oral administration of the polysaccharide fractions of these micro-organisms exerted a similar anti-ulcer effect. The intensity of this activity correlated with the rhamnose content of the polysaccharides, those with more than 60% of rhamnose being the most effective in inducing healing of the gastric mucosa.
Other possible mechanisms of protection induced by probiotics
Alterations in gastrointestinal permeability are considered as an initial step in the development of lesions such as ulcers. Probiotics stabilized the intestinal barrier function in in vitro and animal models and in clinical studies.17 In healthy volunteers we determined that intake of LGG protected the gastric mucosa against alterations of permeability induced by the acute administration of non-steroidal anti-inflammatory drugs (NSAIDs), an important cause of gastroduodenal ulcer.38 Four permeability tests were randomly carried out in every subject using sucrose as a non-invasive marker of gastric permeability: at baseline, after indomethacin administration, after 5 days of live LGG intake before indomethacin administration, and after 5 days of intake of heat-killed LGG before indomethacin administration. Excretion of sucrose in urine was significantly increased by indomethacin while administration of live LGG significantly reduced alteration in gastric permeability induced by the NSAID; heat-killed LGG had no protective effect. These findings suggest that some strains of probiotics may protect the integrity of the gastric mucosal barrier function against the deleterious effects of NSAIDs; they also show that this probiotic effect is only associated with live bacteria. Many factors may explain this protective activity: the stimulation of the expression of gastric mucins,39 decreases in bacterial overgrowth,12 stimulation of local immune responses16 and release of antioxidant substances;40 all these factors are altered in NSAID-associated gastroenteropathy and can be regulated by probiotic ingestion.
Clinical trials with probiotics in H. pylori-colonized subjects
Clinical trials evaluating the use of different probiotic strains in colonized subjects have been recently reviewed by Hamilton-Miller.41 In some of these studies, probiotics were used alone while in others they were used as adjunctive agents in the classical treatment of H. pylori infection. The main outcomes of these studies are the rate or the intensity of colonization, changes in the adverse effects associated with antibiotic administration and the intensity of gastric inflammation.
Utilization of probiotics in association with antibiotics in the treatment of H. pylori
Of the clinical trials evaluating the association of the classical antibiotic and proton pump inhibitor therapy with probiotics for H. pylori eradication in patients with gastroduodenal pathologies, three were randomized but not placebo controlled (Table 1). This is a critical aspect in the analysis of results because one of the main outcomes evaluated in these studies is the intensity of the adverse effects of the antibiotics and proton pump inhibitors, which has a strong subjective component. Three different probiotics were evaluated in these studies: heat-inactivated L. acidophilus LB,42Lactobacillus GG43 and a yogurt (AB yogurt) containing L. acidophilus La5 and B. lactis Bb12.44 Results showed that the administration of L. acidophilus LB was associated with a significant increase in the eradication of H. pylori from 72% to 87% (P < 0.02) without decreases in adverse effects. The study using LGG showed a lower incidence of side effects, especially diarrhoea, bloating and taste disturbances without an improved eradication rate. In the trial with the AB yogurt, side effects were less frequent and a higher proportion of patients completed the full week of antibiotic treatment. In the intention-to-treat analysis H. pylori eradication was also higher in the yogurt group (91% vs. 78%, P < 0.05) but this difference disappeared in the per protocol analysis. Fecal bifidobacteria decreased during antibiotic treatment in both groups of patients but in the yogurt group its numbers returned to basal values more rapidly.
Table 1. Clinical trials using probiotics in association with antibiotics in the treatment of H. pylori colonization
|R, O||Dyspeptic adults (120)||Rabeprazole, clarithromycin, amoxicillin||L. acidophilus LB for 10 days||E.R.: ↗|
A.E.: no effect
|Canducci et al.42|
|R, O||Asymptomatic adults (120)||Pantoprazole, clarithromycin, tinidazole||L. rhamnosus GG, 1.2 × 1010/day for 10 days||E.R.: no effect |
|Armuzzi et al.43|
|R, O||Dyspeptic subjects (160)||Lansoprazole, clarithromycin, amoxicillin||L. acidophilus LA5 + B. lactis Bb12, 1010/day for 4 weeks||E.R.: ↗||Sheu et al.44|
|DB, P, R||Asymptomatic adults (85)||Rabeprazole, clarithromycin, tinidazole||L. rhamnosus GG |
Lactobacillus LA5 + B. lactis Bb12, for 2 weeks
|E.R.: no effect |
|Cremonini et al.45|
|DB, R, P||Asymptomatic adults (52)||clarithromycin||L. johnsonii LA1 acidified milk, 180 mL/day for 3 weeks||E.R.: no effect |
Lower gastric density of Hp
Lower gastric inflammation
|Felley et al.46|
|R||Dyspeptic patients with resistant H. pylori infection (70)||Esomeprazole or pantoprazole, ranitidine bismuth citrate, amoxicillin and tinidazole||L. casei DG, 1.6 × 1010/day for 10 days||E.R.: no effect |
|Tursi et al.47|
Three randomized, double-blind, placebo-controlled studies were carried out with the same objective. Decreases in the side effects of the triple therapy were observed by Cremonini et al.45 in a study in 85 asymptomatic subjects in whom the effects of a single probiotic (LGG or S. boulardii), or a combination of B. lactis and L. acidophilus administered contemporaneously with the triple therapy for 1 week and continued afterwards for an additional week were tested; similar to previous studies no effect on the clearing of H. pylori was observed. In another study in 53 asymptomatic volunteers, the administration of 180 mL of a L. johnsonii La1-acidified milk (LC-1) twice daily for 3 weeks significantly decreased the density of H. pylori in the gastric mucosa and the intensity and activity of gastric inflammation. Clarithromycin eradicated H. pylori in 26% of the subjects and LC-1 did not improve the effect of the antibiotic.46 Side effects decreased during supplementation with L. casei DG in the course of quadruple therapy, resulting in a slight improvement of H. pylori eradication.47
The results of these studies suggest that probiotic supplementation during anti-H. pylori therapy decreases adverse side effects, resulting in better compliance and, in some cases, improved rates of eradication.
Utilization of probiotics alone
Results about the use of probiotics alone in H. pylori-colonized subjects are summarized in Table 2. The supernatant of a culture of L. johnsonii La1 was tested in double-blind fashion in 20 asymptomatic volunteers who also received omeprazole or a placebo; a decrease in the δ Over the Baseline value (DOB) in the 13C-UBT in comparison with the initial determinations was observed; however, H. pylori was not eradicated from the stomach of the affected individuals.30
Table 2. Clinical trials using probiotics alone in H. pylori-colonized subjects
|R, DB, P||Asymptomatic adults (20)||L. johnsonii La1 culture supernatant + omeprazole||13C-UBT results ↘||Michetti et al.30|
|R, DB, P||Asymptomatic children (236)||L. johnsonii La1 |
L. paracasei ST11
1.8 × 109/day for 4 weeks
|13C-UBT results ↘||Cruchet et al.48|
| ||Asymptomatic adults (12)||L. johnsonii La1 8 × 108 every 2 h during 14 h for 2 weeks||13C-UBT results: ↘||Gotteland and Cruchet49|
|R, DB, P||Asymptomatic adults (50)||L. johnsonii La1 acidified milk for 3 and 16 weeks||↘ gastritis |
↘ gastric density of H. pylori
↗ gastric mucus layer
| Pantoflickova et al.50|
|P||Dyspeptic adults (70)||AB-yogurt with L. acidophilus LA5 + B. lactis Bb12, 1010/day for 4 weeks||13C-UBT results ↘||Wang et al.51|
|R||Asymptomatic children (254)||S. boulardii (500 mg/day) + inulin (10 g/day) |
L. acidophilus LB (heat inactivated), 1010/day
for 8 weeks
|Eradication of 12% with Sb, 6.5% with LB||Gotteland et al.52|
|O||Asymptomatic adults (27)||Yogurt with L. casei 03, L. acidophilus 2412, L. acidophilus ACD1 + starter strains, 175 mL/day for 30 days||No effect||Wendakoon et al.53|
|R, P||Asymptomatic adults (14)||L. casei Shirota, 1.95 × 1010, for 3 weeks||No clear effect||Cats et al.66|
|P||Asymptomatic adults (31)||L. gasseri OLL 2716, 2.2 × 109/day, for 8 weeks||13C-UBT results: ↘|
Pepsinogen1/2 : ↘
|Sakamoto et al.54|
|O||Symptomatic children (12)||L. gasseri OLL 2716 for 8 weeks||13C-UBT results: no effect |
H. pylori stool antigen: ↘
|Shimizu et al.55|
The effect of L. johnsonii La1 was further explored in asymptomatic infected school children by Cruchet et al. in Chile.48 In a double blind, randomized, controlled clinical trial, 252 of 326 children (77.3%) 5–16 years of age and H. pylori-positive by 13C-UBT were allocated to one of five groups. Two groups received a product containing live L. johnsonii La1 or L. paracasei ST11 at concentrations >107 CFU/mL every day for 4 weeks; two other groups received the product but with heat-killed La1 or ST11 while the fifth group received the yogurt vehicle as a negative control. A moderate but significant decrease in the results of the 13C-UBT after the treatment compared with basal DOB values was observed in children receiving live La1. The magnitude of the decrease induced by La1 was greater the higher the basal DOB values, suggesting that L. johnsonii La1 exerted a modulating effect on H. pylori colonization by restricting the size of its population in the gastric mucosa. To test whether more frequent intakes exerted a more intense effect, 80 mL of the same commercial preparation was administered to 12 adult asymptomatic volunteers every 2 h for 14 h for 2 weeks.49 This resulted in higher decreases (40%) in DOB values; as in the previous study, higher initial DOB values correlated with greater decreases in DOB after treatment.
The effect of an La1-acidified milk (LC-1) administration was studied in 50 H. pylori-positive healthy volunteers who did not receive any antibiotic treatment in a randomized, controlled, double-blind study; the histology and H. pylori density from gastric biopsies obtained before and after 3 and 16 weeks of treatment were evaluated.50 LC1 decreased the severity and activity of the gastritis (P = 0.04) as well as the density of H. pylori colonization. Interestingly, the thickness of the mucus layer increased during LC1 consumption. Altogether, these results suggest that L. johnsonii La1 may reduce the risk of disorders associated with H. pylori and the high risk of gastric inflammation.
Wang et al. observed that of the two probiotic strains present in AB yogurt, Bb12 and La5, only Bb12 exerted an inhibitory effect in vitro against H. pylori.51 They subsequently administered this yogurt (containing >107 CFU/mL of each strain) to 59 H. pylori-positive individuals twice daily for 6 weeks, while 11 subjects were given a placebo. The authors reported significantly lower DOB values in those receiving the AB yogurt. Moreover, a steeper decrease was observed in those individuals whose initial readings had been the highest, similar to observations by Cruchet et al.48 and Gotteland and Cruchet49 with L. johnsonii La1 in asymptomatic volunteers.
Gotteland et al. evaluated with 13C-UBT the effects of S. boulardii plus inulin and of heat-killed L. acidophilus LB in comparison with triple therapy in colonized schoolchildren;52 the probiotics were administered twice daily for 2 months. Triple therapy eradicated the micro-organism in 66% of the children compared with 12% in those receiving S. boulardii and 6.5% of those receiving L. acidophilus LB. The group receiving S. boulardii also showed a significant decrease in DOB values. To evaluate whether the eradication associated with probiotic intake was a spontaneous process, 81 asymptomatic colonized children were followed with 13C-UBT and without any treatments for 2 months; none of them cleared spontaneously this micro-organism.
Other clinical trials have been carried out with probiotics alone, but with small numbers of subjects and without placebo control. A yogurt containing five strains of lactic acid bacteria with strong in vitro inhibitory activity against H. pylori was investigated by Wendakoon et al.; the intake of 175 mL yogurt thrice daily for 30 days by 27 asymptomatic women resulted in eradication in only one case.53 Similarly, the administration of a product with L. casei Shirota with anti-H. pylori activity thrice daily for 3 weeks to 14 subjects54 produced a slight non-significant suppressive effect.
The effect of 90 g of yogurt with L. gasseri OLL2716 (LG21) administered twice daily for 8 weeks in 29 asymptomatic adults was evaluated by means of the 13C-UBT and the pepsinogen I/ II ratio as a marker of gastric inflammation.55 LG21 decreased significantly DOB values in comparison with baseline measurements and reduced the intensity of gastric inflammation as indicated by the lower pepsinogen I/II ratio. Similar results were obtained with LG21 in children.56
Utilization of other functional dietary components with gastroprotective properties
Many foodstuffs, generally of plant origin and some milk products, have been evaluated in relation to their protective effects on the gastric mucosa and anti-H. pylori properties. For example 16 Chilean red wines and their extracts were tested in vitro against H. pylori and showed an inhibitory activity dependent mainly on the presence of resveratrol, a recognized antioxidant.57 Garlic extracts have also been extensively studied, showing antimicrobial and anti-inflammatory effects in H. pylori-infected Mongolian gerbils.58 Unfortunately, the extensive use of garlic in humans is limited for obvious reasons.
More recently, the investigation in this field has focused on the possible use of cranberries. Cranberry juice is traditionally used in North America to decrease risk relapses of urinary infection; the urine of people drinking cranberry juice inhibits the adhesion of uropathogens to urinary epithelial cells. It has been recently shown that high molecular weight compounds in cranberry and other berries, probably proanthocyanidins, may also interfere with the adhesion of H. pylori to human gastric mucus and to gastric epithelial cells.59, 60 Furthermore, various extracts of berries, alone or in combination, have been shown to inhibit the growth of H. pylori.61 Recently Zhang et al. administered 500 mL of cranberry juice daily for 90 days to 189 subjects in a randomized, double-blind, placebo-controlled trial.6213C-UBT measurements were obtained at baseline and repeated after 35 and 90 days. 13C-UBT was negative in 14 of the 97 subjects (14.3%) who consumed cranberry juice. The majority (11/14) of the negative subjects receiving cranberry juice were negative at both 35 and 90 days; two control subjects also became negative during follow-up. These results are promising and efforts are currently being made to evaluate mixes of different vegetal extracts to obtain additional or synergistic effects vis-à-vis H. pylori.
On the other hand, Horie et al. have elaborated a yogurt containing antibodies against H. pylori urease isolated from the yolk of eggs from immunized hens. The egg yolk was present in a concentration of 1% and this provided 45 mg of the antibody. Intake of this product was associated with a statistically significant decrease in DOB values at 2 and 4 weeks and represents another avenue for the control of H. pylori in the mucosa of the stomach.63
Bovine lactoferrin was used in an open randomized clinical trial in 150 dyspeptic patients as adjunctive agent during a 1-week triple therapy for H. pylori infection.64 The efficacy of triple therapy plus lactoferrin was significantly higher in the treated group than in the control group (P = 0.01). Other milk components such as α-lactalbumin or glycomacropeptide also exert gastroprotective properties.65, 66
The use of probiotics and foodstuffs with bioactive components in H. pylori-colonized subjects with gastric inflammation is supported by many observations. Specific strains of Lactobacillus and Bifidobacterium exert in vitro bactericidal effects against H. pylori through the release of bacteriocins or production of organic acids, and/or inhibit its adhesion to epithelial cells. Such protective effects have been confirmed in animal models. Some clinical trials have evaluated the effect of probiotics in colonized adults and children. Their results indicate that probiotics generally do not eradicate H. pylori but decrease the density of colonization, thereby maintaining lower levels of this pathogen in the stomach; in association with antibiotic treatments, some probiotics increased eradication rates and/or decreased adverse effects due to the antibiotics. On the other hand, the antioxidant and anti-inflammatory properties exerted by probiotics may stabilize the gastric barrier function and decrease mucosal inflammation. These findings confirm that, as suggested by the 2000-Maastricht Consensus Conference on H. pylori, probiotic micro-organisms may be used as a ‘possible’ tool for the management of H. pylori infection and its associated gastric inflammation.