EFFECTIVENESS OF PROBIOTIC SUPPLEMENT ON HELICOBACTER PYLORI INFECTION ERADICATION IN GASTRIC ULCERS

Background: Helicobacter pylori colonizes the gastric mucosa in 50% of the human population. H. pylori infection causes several upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer, duodenal ulcer, and gastric cancer. H. pylori is also associated with a high risk of developing gastric adenocarcinoma. The World Health Organization classifies H. pylori infection as a class 1 carcinogen. Giving probiotics may improve the immune system and suppress the effects of pathogens. However, mixed results were obtained from the use of various kinds of bacteria and fungi as probiotics. Objective: To determine the effectiveness of probiotic supplementation against the eradication of Helicobacter pylori infection in gastric ulcers. Methods: Article searches were conducted using advanced searching by combining MesH Terms and abstracts/titles in the Pubmed, Cochrane Library, and Scopus databases. The search found two selected literature to further conduct a critical assessment. Result: From the results of the literature search, it was found that 2 studies that met the criteria were a clinical trial study from Chang et al. which analyzed the effect of probiotic supplementation and broccoli extract on H. pylori eradication and a clinical trial study from Oh et al. comparing the combination of antibiotics and probiotics with antibiotics alone in H. pylori eradication. The results of these two studies of H. pylori eradication with probiotics got a higher eradication rate, but it was not statistically significant. However, the number of these research subjects was not large enough. Conclusion: The effectiveness uses of probiotics to eradicate H. pylori has not been proven. It will take clinical trials with a sufficient number of subjects and certain probiotic strains to be able to determine the type of strain, dosage, duration of use, and side effects that can be caused.


Introduction
Peptic ulcer disease (PUD), including gastric and duodenal ulcers, is a major health burden in China.The prevalence of PUD in Western countries ranges from 0.1% to 4.7%, with an annual incidence of 0.19% to 0.3%. 1 Peptic ulcer disease is strongly related to chronic Helicobacter pylori (H.pylori) infection.Data from the developed world has shown that in the first decade of the discovery of H. pylori, 95% of duodenal ulcers and 85% of gastric ulcers were associated with H. pylori infection and that the lifetime risk of developing PUD was 3-10-times higher in H. pylori-positive subjects than in their H. pylorinegative counterparts. 2 pylori is a gram-negative microaerophilic bacterium that colonizes the gastric mucosa in 50% of the human population.3 It is estimated that more than 50% of the world population is infected with pylori is also associated with a high risk of developing gastric adenocarcinoma.The world health organization classifies H. pylori infection as a class 1 carcinogen.3,4 The success of antimicrobial therapy depends on adherence to medication, dose, formula, duration, and rate of reinfection.5 During the eradication of H. pylori, the most common problems facing gastroenterologists include (1) antibiotic resistance phenomenon, (2) persistence of bacteria in latent status, (3) degradation of antibiotics in acidic gastric conditions, (4) re-infection, especially in regions with high prevalence, (5) adverse side effects of antibiotics such as diarrhea, nausea, vomit, and abdominal pain, (6) rapid metabolization of antibiotics due to CYP2C19 enzyme, (7) poor compliance of multiple antibiotics.6 In recent years, antibiotic resistance (with high divergence) has led to increased therapeutic failure in eradicating H. pylori with current regimens.There are several recommended regimens for H. pylori eradication.One of them was a combination therapy of proton pump inhibitor, amoxicillin, and clarithromycin or metronidazole.This regimen can be used in cases with low clarithromycin resistance.5 A study by Savoldi et al., 7  Probiotics are defined as live microorganisms which, when in adequate amounts, can provide benefits to the host.8 Probiotics have been used as a preventive and therapeutic agent in several gastrointestinal diseases, such as diarrhea, irritable bowel syndrome, and inflammatory bowel disease.
Giving probiotics will improve the immune system and suppress the effects of pathogens.
In an in vitro study, we found the inhibitory effect of probiotics on the expression of genes

Research Results
The

H
. pylori, with a remarkable variation in the prevalence among countries and within different regions of the same country.Interest in H. pylori resulted from its association with a variety of gastrointestinal conditions, IJCNP : (Indonesian Journal of Clinical Nutrition Physician) 23 DOI : https://doi.org/10.54773/ijcnpIJCNP : (Indonesian Journal of Clinical Nutrition Physician) 2023, 6:1 Open Access Full Text Article ranging from benign to malignant diseases. 2It causes several upper gastrointestinal tract diseases, such as chronic gastritis, peptic ulcer, duodenal ulcer, and gastric cancer.H.
encoding virulence factors.Some probiotics such as Lactococcus lactis, Lactobacillus reuteri, and Lactobacillus bulgaricus produce peptide and nonpeptide antipathogens that suppress the development and adhesion of H. pylori. 9,10Probiotics have various mechanisms to eradicate or restrict H. pylori growth within the stomach of humans, including (1) inhibition of the colonization of H. pylori via IJCNP : (Indonesian Journal of Clinical Nutrition Physician) 2023, 6:1 Open Access Full Text Article conquering gastric epithelial receptors or coaggregation mechanism, (2) anti-H.pylori activity throughout 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. 6Defenses mechanisms against H. pylori infection, which are subdivided into two main mechanisms, including physiological barriers and the immune system.Upon entrance of H. pylori into the stomach, both innate and specific immunity enter the area of infection (lamina propria).Consumption of probiotics has several advantages in strengthening and stimulating the immune system versus this pathogen.Antibacterial activities of probiotics, direct and indirect, are helpful for human health.Therapeutic effects of these bacteria in the gastric tract include immune modulation via interaction with Toll-Like Receptors (TLRs) and anti-H.pylori activity, co-aggregation of invasive bacteria, decrease pH by secretion of short-chain fatty acids, support epithelial barrier integrity, mucin production, as well as promoting immune cells to inhibit gastric inflammatory response, particularly Interleukin-8 production, and induction of immunoglobulin secretions. 6Clinical Question A 40-year-old male patient came to the hospital complaining of nausea, frequent burping, bloating and burning sensation in the epigastric that interrupted activities.The symptoms appear several times and usually get better after eating.But now the complaints persist and feel worsening.He is a field worker who often skips meals and regularly drinks coffee.He often consumes herbal medicine whenever he feels tired after work.The patient's blood pressure was 140/100 mmHg, pulse 80 times per minute, breath 20 times per minute.The body weight was 70 kg, height 154 cm, BMI 29,5 kg/m 2 .In addition, the patient was also subjected to a blood examination of Hemoglobin 11 g/dL, leukocytes 15,400/µL and platelets 354,000/µL.There is a history of diabetes mellitus for a couple of years.He was diagnosed with gastric ulcer caused by Helicobacter pylori infection and treated with a combination of proton pump inhibitor, amoxicillin and clarithromycin.The patient asked whether probiotic consumption can be beneficial to improve his condition or not.Methods The article searches were conducted using basic and advanced searching methods by combining Pubmed, Cochrane Library, and IJCNP : (Indonesian Journal of Clinical Nutrition Physician) 25 DOI : https://doi.org/10.54773/ijcnpIJCNP : (Indonesian Journal of Clinical Nutrition Physician) 2023, 6:1 Open Access Full Text Article Scopus databases.The search was carried out on December 19, 2021.Keywords were entered in the MeSH Terms and title/abstract categories.The articles included in the search were systematic reviews, metaanalyses, and randomized controlled trials within the last 5 years.Studies on animals, studies that were not fully available, and studies other than in English were not included in the search.Titles and abstracts were reviewed, articles that did not meet the eligibility criteria and PICO were excluded, and duplication screening was carried out.A critical study was carried out using tools from the Center for Evidence-Based Medicine, Oxford Center for Evidence-Based Medicine.
search results yielded 72 articles from Pubmed 7 articles from Cochrane Library, and 46 articles from Scopus.After the search results were obtained, a screening of duplicated articles was conducted using the Mendeley program.A subsequent screening test was carried out by comparing the title and abstract to the suitability of the PICO.Eligibility criteria such as full text and limitations on the publication of articles within the last 5 years were applied before conducting a critical review of the articles obtained.After screening duplication and selecting articles according to eligibility criteria, 2 literature from Chang et al., 11 and Oh et al., 12 were found to be relevant and could be analyzed to answer clinical questions (Figure 1).

Figure 1 . 1 Open
Figure 1.PRISMA's Flow Chart showed an increase in H. pylori Open Access Full Text Article namely 100% and 90%, respectively.However, this result is not statistically significant because the number of research subjects is small. 12his study also did not get a sufficient number of subjects to get meaningful results.In addition, the lifestyle of the subjects, such as alcohol consumption and smoking, changes in gut microbiota before and after the intervention were also different.Nutrient intake factors also play an important role in changes in the gut microbiota.In previous studies, it was reported that the positive effect of probiotics in the eradication of H. pylori was quite high using several strains such as pylori eradication rate from each group.It was found that the eradication rate in the probiotic group was higher than the antibiotic group, IJCNP : (Indonesian Journal of Clinical Nutrition Physician) 2023, 6:1