Bacillus Probiotics With Bismuth Quadruple Therapy for Helicobacter Pylori Infection
brief summary
Helicobacter pylori (H. pylori) is a very common gastrointestinal disease that colonises the human gastric mucosa and is a primary risk factor for chronic gastritis, peptic ulcer disease, and gastric cancer. The standard first-line treatment for H. pylori eradication is bismuth-containing quadruple therapy. While effective, this aggressive, multi-antibiotic regimen frequently induces significant gastrointestinal adverse effects and severe disruption of the normal gut microbiota (dysbiosis). These side effects often lead to poor patient compliance, which in turn contributes to treatment failure and the increasing global challenge of antibiotic resistance. Emerging clinical evidence strongly supports the use of probiotics as an adjuvant therapy to alleviate antibiotic-associated side effects and significantly aid in restoring intestinal balance. Spore-forming Bacillus species, specifically Bacillus clausii, Bacillus subtilis, and Bacillus coagulans, are particularly advantageous due to their natural resistance to acidic gastric conditions and concurrent antibiotic administration, allowing them to remain viable and active during the intensive eradication therapy. This clinical trial is designed as a randomised, double-blind, placebo-controlled study to evaluate the clinical efficacy, adverse effects, and treatment adherence of a standard four-drug bismuth-containing regimen for the treatment of H. pylori infection when combined with single-strain and multi-strain Bacillus probiotics. The trial is conducted in the Gastroenterology Department of Tam Anh Hospital. 336 participants diagnosed with H. pylori infection and prescribed the standard 14-day bismuth-containing quadruple therapy are randomly divided and allocated to receive either a single-strain probiotic (LiveSpo Clausy), a multi-strain probiotic (LiveSpo DIA 30), or an identical placebo. Over 8 weeks of follow-up, participants will be assessed at predefined time points for antibiotic-associated adverse events, gastrointestinal symptoms, stool form, treatment adherence, and Helicobacter pylori eradication status. Stool samples will be collected before and after treatment to evaluate faecal IgA levels, the presence of Bacillus strains, and changes in gut microbiota using real-time PCR, ELISA, and 16S rRNA sequencing.
detailed description
Helicobacter pylori (H. pylori) infection affects roughly half of the world's population, making it a very common digestive disease. In developing countries, infection rates are especially high, with 85-95% of the population potentially infected with H. pylori, making this disease a major public health concern. H. pylori mainly infects and lives in the mucous membrane of the stomach lining, enabling it to persist for long periods and lead to chronic infection. Its survival in the stomach's harsh acidity is primarily due to urease, an enzyme that breaks down urea into ammonia, neutralizing the stomach acid. In Vietnam, historically, clarithromycin-based triple therapy achieved eradication rates exceeding 90%. However, rising global antibiotic resistance has reduced its efficacy to below 70%, leading to its removal from first-line recommendations in regions with high resistance. As a result, bismuth-containing quadruple therapy, which includes a proton pump inhibitor (PPI), tetracycline, metronidazole, and bismuth, has become the standard first-line and rescue treatment for H. pylori eradication.
While this regimen is highly effective, yielding eradication rates between 90.4% and 99.3%, it frequently induces significant gastrointestinal adverse effects. Clinical data indicate that 54.1% to 67.0% of patients experience symptoms such as dizziness, nausea, vomiting, diarrhea, black stools, fatigue, and anorexia. Furthermore, the high-dose administration of tetracycline and metronidazole causes severe disruption of the normal gut microbiota (dysbiosis). This dysbiosis is characterized by a marked decrease in beneficial microbial populations, such as Bacteroidetes and Actinobacteria, alongside a concerning overgrowth of opportunistic pathogens, such as Proteobacteria. These severe side effects often lead to poor patient compliance, causing patients to reduce dosages or prematurely discontinue therapy. This lack of adherence, in turn, contributes to treatment failure and exacerbates the increasing global challenge of antibiotic resistance.
The use of spore-forming probiotic strains from the genus Bacillus in Helicobacter pylori eradication regimens has recently garnered considerable attention within the scientific community, yielding promising outcomes in randomized controlled trials (RCTs). Multicenter studies have demonstrated that supplementation with Bacillus clausii alongside antibiotic regimens significantly reduces the incidence of antibiotic-associated diarrhoea (AAD) and other gastrointestinal symptoms, including nausea and a bitter taste. This, in turn, enhances drug tolerance and treatment adherence among patients. Additionally, research on Bacillus subtilis and Bacillus coagulans offers substantial medical evidence concerning their direct and indirect mechanisms of action. In vitro studies indicate that B. subtilis may inhibit H. pylori growth through secretion of natural antimicrobial compounds, particularly amicoumacin A, while other Bacillus-derived bacteriocins and lipopeptides may contribute to broader antimicrobial activity. In contrast, B. coagulans has demonstrated efficacy in modulating local immune responses, reducing inflammatory cytokines, and preserving the integrity of the gastric mucosa against bacterial damage.
official title
Clinical Efficacy and Gut Microbiota Effects of High-Dose Single-Strain and Multi-Strain Bacillus Probiotics as Adjunctive Therapy to Bismuth Quadruple Therapy for Helicobacter Pylori Eradication: A Randomised, Double-Blind, Placebo-Controlled Trial