Available online on 15.06.2022 at http://jddtonline.info

Journal of Drug Delivery and Therapeutics

Open Access to Pharmaceutical and Medical Research

Copyright  © 2011-2022 The  Author(s): This is an open-access article distributed under the terms of the CC BY-NC 4.0 which permits unrestricted use, distribution, and reproduction in any medium for non-commercial use provided the original author and source are credited

Open Access   Full Text Article                                                                                                                                                                 Research Article 

A comparative prospective study in the management of Helicobacter pylori infection using Lactobacillus reuteri Vs conventional therapy

Syed Ibrahim Hassan¹, Mohammed Baleeqh Uddin²*, Mohd Ehtesham Kaunaine², Sumayya Sultana², Syeda Aleena Samreen², Mohd Mohiuddin³

1. Department of Gastroenterology, Princess Esra Hospital, Hyderabad, India
2. Department of Pharmacy Practice, Deccan School of Pharmacy, Hyderabad, India
3. Department of Pharmacology, Deccan School of Pharmacy, Hyderabad, India

BACKGROUND AND AIM

Helicobacter pylori (H. pylori) is a widespread microaerophilic, gram-negative, spiral- shaped bacterium that infects at least 50% of the global population. H. pylori can withstand the acid environment of the stomach because of its ability to adhere to the gastric mucosa, colonizing the mucosal lining of the stomach¹,². The majority of H. pylori carriers remain asymptomatic. But it is associated with many gastrointestinal diseases such as peptic ulcer, gastric cancer, and rarely mucosa-associated lymphoid tissue lymphoma. H. pylori infection has become a remarkable worldwide health problem³. The prevalence of H. pylori infection differs between regions of the developing world. In some developing countries, the prevalence of H. pylori is about 80–90^%4.The eradication of H. pylori has become a challenge in many parts of the world. Therapeutic options for H. pylori infection include different combinations of proton pump inhibitors associated with two or three antibiotics for the purpose of eradication. Alas, this approach has higher risks of side effects that lead to poor compliance and this demands the introduction of new antimicrobial agents. Few researchers proved the use of probiotics during the first-line H. pylori therapy that improved the patient’s compliance and dropped gastrointestinal symptoms^5,6.

A probiotic is defined as a living microbial species that shows a constructive effect on bowel microecology on administration. The most studied probiotics are lactic acid-producing bacteria, particularly Lactobacillus⁷. Probiotics have proven beneficial in reducing the side effects of antibiotics and increases patient compliance. Lactobacillus reuteri (L. reuteri) is one species of lactobacillus which is safe for human consumption and also exerts an inhibitory effect on the settlement of human gastric mucosa by H. pylori⁸. This strain acts against H. pylori in the stomach by specifically binding and co-aggregating. Binding to L. reuteri masks surface structures of H. pylori and severely impedes its motility. The aggregated H. pylori no longer adhere to the gastric mucosa and the Lactobacillus- Helicobacter complexes are flushed out of the stomach⁹. Several studies reported supplementation with L. reuteri in both symptomatic and non-symptomatic H. pylori infected subjects shown a clear reduction of infection load after 4 weeks of use and improvement in symptoms associated with the infection. In addition to this, certain revealed L. reuteri strains together with proton pump inhibitors (PPI) in the absence of antibiotics, may eradicate H. pylori infection at least in 50% of the treated patients^10,11.

The aim of our study was to compare the effectiveness of a probiotic and conventional antibiotic triple therapy in the management of helicobacter pylori infection in patients with severe gastrointestinal manifestations.

METHODS

The present prospective observational study was carried out at the Department of Gastroenterology, Princess Esra Hospital, Shah Ali Banda, Hyderabad for a period of six months. People with the following criteria were allowed to participate in this study: a) Confirmed H. pylori infection; b) Age of 18 to 70 years. Patients with the following criteria were excluded: a)Chronic diseases such as renal failure and cirrhosis, pan gastritis, peptic ulcers; b) Malignancies; c) Gall bladder disorders; d)Prior upper digestive tract surgery; e)Prior probiotic therapy in the last month; f) Antibiotics, PPIs and H2RA therapy in the previous 4 weeks; g) Known allergy to antibiotics.All patients gave written informed consent before participation. A complete history of the patients, laboratory investigations, treatment chart were extracted from their medical records and documented in a suitably designed individual case record form. This included their age, gender, gastrointestinal symptoms, report of Rapid Urease Test (RUT), drug chart. The changes in symptoms were recorded using the Gastrointestinal Symptom Rating Scale (GSRS) at baseline and post treatment.

Study outcomes

The primary outcome was comparing the effectiveness of probiotic (L. reuteri) and conventional triple therapy in the suppression of the bacteria confirmed by a RUT performed post-treatment. The secondary endpoint was to assess the improvement in the gastrointestinal symptoms using the GSRS.

Statistical analysis

The data was analyzed using Microsoft Excel and Statistical Package for Social Service (SPSS) Version 20. Means and standard deviations (SD) were calculated for continuous variables, while frequencies and percentages were calculated for categorical variables. A dependent t-test was used to compare the mean scores before and after treatment. One-way analysis of variance (ANOVA) was used to compare the mean scores of three different groups. A chi-square test was carried out for the analysis of categorical variables. P values less than 0.05 were considered statistically significant at a 5% level of significance with a confidence interval of 95%.

RESULTS

Baseline characteristics

A total of 105 patients with confirmed H. pylori infection, of which 42% were males and 58% were females participated in the study. They were randomized into three study groups namely Group I, II and III. Each group consists of 35 patients. Patients in Group I treated with L. reuteri alone. Group II patients treated with L. reuteri and PPI. Patients of Group III treated with conventional triple therapy. The mean age of three group patients were 38.03±10.68, 34.00±13.36 and 36.11±13.37 years. The three treatment groups were similar in their baseline characteristics [Table 1& Figure 1-2].

Table 1: Baseline Characteristics

Figure 1: Age Wise Distribution

Figure 2: Distribution Based on Gender

Comparison of treatment efficacy

All patients were tested positive before treatment in rapid urease test. Only 12% were tested positive and 88% of patients were tested negative post -treatment. Eradication rate noted in L. reuteri only treatment was 86%, eradication rate noted in L. reuteri+ ppi was 86% and in antibiotic group was 92%.At the end of therapy there was no significant difference in the report of rapid urease test between three groups (p = 0.7039) [Table 2& Figure 3]

Table 2: Report of RUT after Treatment

Figure 3: Rapid Urease Test

Assessment of gastrointestinal symptoms using GSRS 

The baseline GSRS scores for three different groups were 2.73±0.49, 2.39±0.65 and 2.57±0.53 respectively [Table 3 & Figure 4] with no significant difference (p = 0.0568).

Table 3: Comparison of Baseline GSRS Score

Figure 4: Comparison of Baseline GSRS Score

After treatment, GSRS scores for three treatment groups were 2.03±0.43, 1.81±0.59 and 1.83±0.46 respectively [Table 4& Figure 5-7]. Patients with three different treatments have shown significant improvement in gastrointestinal symptoms (p < 0.001). When the percentage of improvement in symptoms were evaluated, we found that patients receiving conventional triple therapy marked higher improvement (29%) whereas the other two groups (Group I & II) shown 26% and 24% of improvement. Three different treatment patterns were well tolerated by all patients and no serious adverse events were reported during the period of intake. 

Table 4: Comparison of GSRS Score before and after Treatment in Group I

Figure 5: Comparison of GSRS Score before and after Treatment in Group I

Figure 6: Comparison of GSRS Score before and after Treatment in Group II

Figure 7: Comparison of GSRS Score before and after Treatment in Group III

DISCUSSION 

H. pylori infection is considered endemic in many countries.   Even though various therapeutic regimens (dual therapy, triple therapy, quadruple therapy, and sequential therapy) are available currently, failure of treatment remains a major problem in medical practice¹². There are several factors that plays a role in eradication failure. Among those, the most pertinent is patient’s poor compliance and antibiotic resistance. Probiotics were studied to lower the frequency of adverse events related to H. pylori therapy thereby it improves the patient’s compliance¹³. Therefore, it is essential to include probiotics as an adjunct therapy to the current treatment regimen of H. pylori infection to achieve higher eradication rates.

Microorganism belongs to the genera Bifido bacterium, Lactobacillus, Saccharomyces, and Bacillus were the commonly used probiotics in humans. Based on the evidence, the most considered probiotics are lactic acid bacteria especially Lactobacillus and Bifido bacterium. The favourable effects of the above probiotics seem to be strain-specific and dose-dependent¹⁴.In the present study, we have used L. reuteri since the administration of L. reuteriis considered safe in children as well as in adults and also diminishing the severity of gastrointestinal symptoms. In addition to this, there are certain indirect effects like decrease of inflammatory cytokines, restoration of IL-10, suppression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) activation in most of the cases¹⁵. Hence, L. reuteri is promising when aiming at achieving the reduction of bacterial levels, modulating the immune response, controlling inflammation, or inhibiting the adherence of H. pylori to the gastric epithelium by reducing its motility.

Our study compared the effectiveness of three treatment patterns of H. pylori infection i.e., L. reuteri alone, L. reuteri with PPI, and conventional triple therapy. We analyzed the existence of H. pylori infection in patients of different ages and observed that the incidence of H. pylori infection varies with age. However, a significant difference doesn’t exist between the groups. Several studies showed that the prevalence of H. pylori infection increased with age in the general population in developed and developing countries⁸. Our study demonstrates a female predominance in H. pylori positivity and is similar to Agah S et al¹⁶ which reported female gender was one of the significant factors that predicted H pylori infection in gastric ulcer patients.

The rapid urease test is an indirect popular diagnostic test that is simple, rapid, and cheap that is commonly used in clinical practice. The RUT detects the presence of H. pylori based on the presence of urease in or on the gastric mucosa¹⁷. Our study compared the outcome of treatment based on RUT report that was taken post-treatment. The overall H. pylori eradication was achieved in 88% of the patients treated. Group I & II have shown 86% of eradication rate whereas Group III had shown 91% of eradication rate which is higher than reported by Adeyemi EO et al¹⁸. 

Interestingly, there was a statistically significant decrease in GSRS score after 15 days and 28 days of treatment. Refinement of clinical manifestations is a marker of successful therapy.  All the three treatment groups showed improvements in the GSRS after therapy, but the conventional triple therapy group showed more but with a difference of only 3%. These improvements of symptoms should promote patients for more compliance to treatment.

This is a prospective observational study to generate a hypothesis further clinical trail and large multicentre studies are needed to evaluate better current H. pylori therapy with L. reuterias adjuvant therapy.

CONCLUSION

Our study concluded that L. reuteri has the potential to suppress H. pylori infection, and also may lead to an improvement of gastrointestinal symptoms associated with H. pylori. Though conventional triple therapy of H. pylori has shown an increased eradication rate and significant improvement in gastrointestinal symptoms, there was no great difference when compared with L. reuteritreated patients.The overall data suggests that L. reuteri is recommended for a better eradication rate and reduced gastrointestinal symptoms. Hence, further studies on a larger number of patients are required to explain the real clinical application of L. reuteri. In addition to this, future studies should concentrate on elucidating an ideal duration of L. reuteri administration.

Ethical approval

This study was conducted as per the protocol and principles of the Declaration of Helsinki. The study was approved by the Ethical Committee of Deccan College of Medical Sciences with IRB project No.2021/32/003

Conflicts of interest

Authors have declared that no conflict of interests exists.

Acknowledgement

We would like to thank the staff of Princess Esra Hospital and Deccan School of Pharmacy.

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