Are probiotics the new gold standard in managing Helicobacter pylori infections?

Helicobacter pylori (H. pylori) infection is considered one of the most common bacterial infections reported globally, especially in Eastern Europe, Africa, and most Asian countries [1]. With prevalence of Helicobacter pylori infections increasing with great magnitude in developing countries (1), this notorious bacteria is estimated to affect half of the world's population.

Ample evidence now suggests that H. pylori are the etiologic agent behind gastric diseases like peptic ulcer disease, chronic gastritis, gastric adenocarcinoma, mucosa-associated lymphoid tissue lymphoma and certain extra-gastrointestinal disorders; eradication of H. pylori improves peptic ulcer disease condition and thus reduces the risk of development of gastric cancer. (2,3)

Triple therapy with proton pump inhibitors combined with clarithromycin and amoxicillin or metronidazole, considered to be the standard drug therapy in managing H. pylori, is losing popularity rapidly, owing to the increasing prevalence of H. pylori resistance to antibiotics(4). A decrease in efficacy rates of triple-drug therapy below 80% has been recorded lately(5), urging medical professionals to put the focus on other novel therapeutic approaches with fewer adverse effects.

Probiotics, either as a monotherapy or with antibiotics as a combination therapy, have been in the limelight for some time now. Probiotics are living microorganisms that, when administered in adequate amounts, can improve microbial balance in the intestine and exert positive health effects on the host(6), including beneficial effects on the prevention of intestinal infections,(7) cardiovascular diseases(8), cancer (9), and allergy manifestations.(10) Accumulating research now highlights that probiotics can improve H. pylori eradication and reduce side effects caused during therapy.(11) Among the most widely investigated probiotics against H. pylori, Lactobacillus and Bifidobacterium call for special attention due to their extensive beneficial effects on the host, including promotion of gut maturation and integrity, antagonism against pathogens, and modulation of the immune system. (12)

This article summarises the study testimonials supporting the potency of probiotics in managing H. pylori while exploring the mechanisms behind the same. 

Mechanism of action of probiotics against H. pylori infection- Probiotics work via a diverse range of mechanisms to restrict H. pylori growth within the stomach of humans. Studies suggest that probiotics can have a dual role in fighting against H. pylori infection. They diminish the frequency of gastrointestinal adverse events caused by antibiotic therapy while increasing the eradication rates concomitantly. The ways probiotics work (13) have been listed below-

(1) Inhibition of the colonization of H. pylori via conquering gastric epithelial receptors or co-aggregation mechanism, (2) anti-H. pylori activity through the production of bacteriocins, organic acids, as well as biosurfactants, (3) supportive role in intestinal tissues by promoting mucin synthesis, (4) modulation of immune system response, (5), induction of antigen-specific antibodies, and (6) reduction of stomach inflammation.

Quoting notable trials-

1. Probiotics as a single therapy in H. pylori treatment-

• Michetti et al[14] studied for the first time the effect of probiotics [L. acidophilus (La1)] on the H. pylori colonization in humans. The study showed that the density of bacterial load diminishes in the probiotic group of asymptomatic patients.
• Wang et al[14] revealed that after intake of B. lactis Bb12 and L. acidophilus La5 in H. pylori-infected adults a decrease in urea breath test values was detected. The bacterial load was evaluated by the semi-quantitative 13C-urea breath test in subjects treated with L. johnsonii La1, L.brevis CD2 lyophilized bacteria, B. bifidum BF-1, L. reuteri ATCC 55730, L. gasseri OLL 2716, and with multispecies probiotics such as a combination of L. reuteri DSM 17938 and L. reuteri ATCC PTA 6457 or combination of L. rhamnosus GG, L. rhamnosus LC705, P. Freudenreichii JS and B. lactis Bb12. Regardless of the used probiotics, the authors reported a significant decrease in 13C-urea breath test values in the probiotic group of studied patients.

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Extrapolating the above studies, it becomes clear that when used as monotherapy, probiotics diminish the bacterial load in patients with H. pylori infection. 

Probiotics as adjuvant therapy in standard eradication protocols -

• A meta-analysis evaluating the effectiveness and safety of probiotics in facilitating the eradication of H pylori infection included forty randomized controlled trials with 8924 patients.The results indicated that probiotics improved the eradication rate and reduced the incidence of side effects when administered before or throughout the elimination treatment of H Pylori or using probiotics for more than 2 weeks. Lactobacillus and multiple strains exerted better eradication effects due to a strong antibacterial effect, potentially increasing humoral and cellular immunity. Saccharomyces needed to be combined with other probiotics to more substantially improve the eradication effect. 15
• Similar findings were observed by Canducci et al (14) who noted an increased H. pylori eradication rate in the Lactobacillus group when compared to controls.
• Tong et al (14) concluded that eradication rates were 70% in the control group and 84% in the probiotic supplemented group, which is a statistically significant difference (RR = 2.09, 95%CI: 1.28-3.41). In addition, this meta-analysis revealed that adding probiotics to standard eradication protocols reduces adverse effects during treatment (25% vs 39%, RR = 0.44, 95%CI: 0.30-0.66). The positive impact on diarrhea and taste disturbance was most prominent.
• Demonstration that L. reuteri ATCC 55730 is able to colonize the stomach and duodenum encouraged studies regarding the effect of this strain on H. pylori eradication rates and the frequency of side effects [14]. Ojetti et al evaluated the treatment regime of 90 patients. L. reuteri supplementation was concomitantly used for 14 days with second line therapy receiving PPI and antibiotics in patients infected with H. pylori. Probiotic supplementation increased the eradication rate in treated patients (group 1: 36/45, 80%; group 2: 28/45 62%; P < 0.050) and the incidence of side effects associated with antibiotic therapy was also significantly lower in the probiotic group.
• Francavilla et al [14] compared the eradication rates and antibiotic adverse effects in 40 H. pylori positive subjects who were receiving placebo or L. reuteri (108 CFU) once a day for a month. At the end of the trial patients received standard 10-d sequential eradication therapy. Four week supplementation with L. reuteri was effective in lowering gastrointestinal adverse effects and also in reducing bacterial load. 
• Effect of pre-treatment with L. gasseri OLL2716 on first-line eradication therapy was studied in a trial published by Deguchi et al[14]. Overall eradication was significantly better in the studied probiotic group [intention to treat (P = 0.018)/per-protocol (P = 0.041)].
• Chitapanarux, Taned, et al. (16) in a randomized, double-blind placebo controlled study evaluated the effect of Bifidobacterium longum on H. pylori eradication in patients on standard triple therapy regimen. The results showed that B. longum improved the H. pylori eradication rate as well as adverse events associated with the antibiotic therapy. 

Therapeutic effects of probiotics against H. pylori infection in children-

● Probiotics can significantly increase H. pylori eradication rate particularly in patients receiving Lactobacillus spp. and Bifidobacterium spp. supplementation. These probiotics have a high potential against H. pylori infection using various mechanisms. In addition, probiotics can alter the gut microbiota to reduce gastrointestinal symptoms and drug side effects.13

● Recently, two meta-analyses have evaluated the clinical effects of probiotics in the treatment of H. pylori infection in children. Li et al. evaluated data from 508 symptomatic children; the pooled ORs for H. pylori eradication rate by intention-to-treat (ITT) and per-protocol (PP) analysis in children who had received probiotic supplementation and control group was 1.96 (95% CI: 1.28–3.02) and 2.25 (95% CI: 1.41–3.57), respectively [13].

● In another study, Fang et al.(13) analyzed the clinical efficacy of Lactobacillus supplemented triple therapy in 484 children, and found that the relative risk (RR) of curing rate in the Lactobacillus-treated group was significantly higher than control group (RR: 1.19; 95% CI: 1.07–1.33); diarrhea was also significantly reduced (RR: 0.3; 95% CI: 0.10–0.85) in the probiotic group 

Take home message- 

1. H. pylori is regarded as a difficult-to-treat infection with high recurrence rates, mainly because of acquired resistance to commonly used antibiotics.

2. The last decade has noted a growing interest in using probiotics in conjunction with antibiotic regimens to eradicate H. pylori.

3. The benefits of probiotic therapy in H. pylori cases are increased eradication and improved tolerability, ultimately resulting in improved patient compliance 

The way ahead-

With research highlighting approximately more than 20 % prevalence rates of antibiotic resistance against H. pylori(17), varying in specific areas and among certain populations, an alternative therapy is the need of the hour. With accumulating evidence supporting the benefits of using probiotics as an adjunct to standard therapy, the management of H. pylori infections is on the verge of undergoing a much-needed revolutionary change.  

The above story has been published under MD Brand Connect Initiative. For more details on probiotics click on this link

References

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2. Keikha M. Is there a relationship between Helicobacter pylori vacA i1 or i2 alleles and development into peptic ulcer and gastric cancer? A meta-analysis study on an Iranian population. New Microbes New Infect. 2020;36:100726.

3. Keikha M. The association between Helicobacter pylori eradication in peptic ulcer patients and gastric cancer? Investigation in an East-Asian population. Trends Pharm Sci. 2020;6(4):279–82.

4. Hu Y, Zhang M, Lu B, Dai J. Helicobacter pylori and antibiotic resistance, a continuing and intractable problem. Helicobacter. 2016;21(5):349–63

5. Jaka, Hyasinta, et al. "Predictors of triple therapy treatment failure among H. pylori infected patients attending at a tertiary hospital in Northwest Tanzania: a prospective study." BMC Infectious Diseases 19.1 (2019): 1-7.

6. FAO/WHO (2002) Guidelines for the evaluation of probiotics in food.Food and Agriculture Organization of the United Nations/World Health Organization, London 

7. Isolauri, Erika, P. V. Kirjavainen, and S. Salminen. "Probiotics: a role in the treatment of intestinal infection and inflammation?." Gut 50.suppl 3 (2002): iii54-iii59.

8. Thushara, Ram Mohan et al. "Cardiovascular benefits of probiotics: a review of experimental and clinical studies." Food & function vol. 7,2 (2016): 632-42. doi:10.1039/c5fo01190f

9. Śliżewska, Katarzyna et al. "The Role of Probiotics in Cancer Prevention." Cancers vol. 13,1 20. 23 Dec. 2020, doi:10.3390/cancers13010020

10. Doron, Shira, and Sherwood L Gorbach. "Probiotics: their role in the treatment and prevention of disease." Expert review of anti-infective therapy vol. 4,2 (2006): 261-75. doi:10.1586/14787210.4.2.261

11. Shi, Xiaoguang et al. "Efficacy and safety of probiotics in eradicating Helicobacter pylori: A network meta-analysis." Medicine vol. 98,15 (2019): e15180. doi:10.1097/MD.0000000000015180

12. Goderska, Kamila, Sonia Agudo Pena, and Teresa Alarcon. "Helicobacter pylori treatment: antibiotics or probiotics." Applied microbiology and biotechnology 102.1 (2018): 1-7.

13. Keikha, Masoud, and Mohsen Karbalaei. "Probiotics as the live microscopic fighters against Helicobacter pylori gastric infections." BMC gastroenterology 21.1 (2021): 1-18.

14. Homan, Matjaž, and Rok Orel. "Are probiotics useful in Helicobacter pylori eradication?." World Journal of Gastroenterology: WJG 21.37 (2015): 10644.

15. Shi, Xiaoguang et al. "Efficacy and safety of probiotics in eradicating Helicobacter pylori: A network meta-analysis." Medicine vol. 98,15 (2019): e15180. doi:10.1097/MD.0000000000015180

16. Chitapanarux, Taned, et al. "Effect of Bifidobacterium longum on PPI-based triple therapy for eradication of Helicobacter pylori: a randomized, double-blind placebo-controlled study." Journal of Functional Foods 13 (2015): 289-294.

17. Ghotaslou, Reza et al. "Prevalence of antibiotic resistance in Helicobacter pylori: A recent literature review." World journal of methodology vol. 5,3 164-74. 26 Sep. 2015, doi:10.5662/wjm.v5.i3.164