Introduction

Treatment of Helicobacter pylori(H. pylori)
infection can alter the gut
microbiota and lead to gastrointestinal
adverse effects (AEs)1

  • H. pylori infection is treated with a combination of antibiotics and proton pump inhibitors (PPIs) for 1 week
  • Antibiotics used for the treatment of H. pylori infection, such as amoxicillin, can have prolonged negative impacts on the gut microbiome which may take several weeks to recover if it all2
    • Microbial diversity is decreased, effecting the abundance of beneficial commensals and detrimental microorganisms3

PPIs and the gut microbiome

  • Use of PPIs to treat H. pylori infection alters the composition of the gut microbiome,4 which may:
    • Increase the risk of enteric infections and bacterial translocation to the blood5
    • Promote the onset of gastrointestinal disorders6
  • There are at least two known mechanisms of this effect7
    • Direct targeting of bacterial proton pumps
    • Inhibition of gastric acid secretion (altering the gut microenvironment)

PPI, proton pump inhibitor

Study Objective

A previous study using a vial formulation of B. clausii in patients undergoing
7-day triple therapy for H. pylori infection also showed a
decrease in the incidence of diarrhea compared to patients given a
placebo8

Probiotics may reduce gastrointestinal adverse effects associated with H. pylori infection9

This study aimed to assess the efficacy of a spore-based probiotic containing spores of four antibiotic-resistant Bacillus clausii (B.clausii) strains (Enterogermina®) in capsule formulation in reducing and preventing the AEs associated with H. pylori eradication therapy

Study Design

A randomized, double-blind, single-center, phase IIIB study conducted between 2003–2004

Primary outcome:

  • Presence of diarrhea at week 1

Secondary outcomes:

  • Number of days without diarrhea
  • Daily frequency of diarrhea
  • Presence/absence of other gastrointestinal symptoms during weeks 1–2

aDuring week 1, all patients received clarithromycin 500 mg twice daily, amoxicillin 1 g twice daily and rabeprazole 20 mg twice daily.

Results

Patient disposition and demographics

Demographic Data B. Clausii
(n=65)		 Placebo
(n=65)
Male, n (%) 3 28 (43.08) 26 (40.00)
Female, n (%) 37 (56.92) 39 (60.00)
Age, years, mean (SD) 44.23 (13.48) 42.38 (13.02)

Prevention of adverse effects by Bacillus clausii capsules

Incidence of symptoms

  • In both week 1 and week 2, there was significantly less diarrhea in the B. clausii treatment group

Plots show relative risk with 95% confidence intervals

Prevention of adverse effects by Bacillus clausii capsules

Days without symptoms

  • Patients receiving B. clausii had significantly more days without diarrhea than patients receiving placebo (6.25 vs 5.86; p=0.0304)

Safety and tolerability

  • Three AEs were reported in the study in two placebo recipients:
    • Gastrointestinal mycosis and gastroenteritis (both in the same patient); mild aphthous stomatitis (one patient)
  • There were no serious AEs or AEs related to study treatment

Patients' global assessment of tolerability was similar in
both treatment groups

Patients' global assessment of tolerability was similar in
both treatment groups

AE, adverse effect

Conclusions

Enterogermina®:

   significantly reduced the incidence of diarrhea was well tolerated

in patients receiving eradication therapy H. pylori eradication therapy

This study suggests that B. clausii probiotics can ameliorate the negative effect of PPIs on the gut microbiota.

AE, adverse effect; PPI, proton pump inhibitor

Summary

Treatment of H. pylori infection with antibiotics and/or PPIs can cause gastrointestinal AEs

Probiotics have been shown to reduce AEs

130 patients receiving H. pylori eradication therapy were randomised (1:1) to receive Enterogermina® or placebo

Frequency of diarrhea (primary endpoint)
Week 1: 29% in the B. clausii group compared with
48% in the placebo group (p=0.03)
Week 2: incidence remained significantly lower

Number of days without symptoms
Number of days without diarrhea was 6.25 with B.
clausii vs 5.86 with placebo (p=0.0304)

Enterogermina® was well tolerated and reduced incidence of gastrointestinal AEs

AE, adverse effect; PPI, proton pump inhibitor
Prevention of adverse effects by Bacillus clausii capsules

    1. Bhalodi AA, van Engelen TSR, Virk HS, Wiersinga WJ. Impact of antimicrobial therapy on the gut microbiome. J Antimicrob Chemother. 2019 Jan 1;74(Suppl 1):i6-i15
    2. Lin H, Wang Q, Yuan M, Liu L, Chen Z, Zhao Y, Das R, Duan Y, Xu X, Xue Y, Luo Y, Mao D. The prolonged disruption of a single-course amoxicillin on mice gut microbiota and resistome, and recovery by inulin, Bifidobacterium longum and fecal microbiota transplantation. Environ Pollut. 2020 Oct;265(Pt A):114651.
    3. Zimmermann P, Curtis N. The effect of antibiotics on the composition of the intestinal microbiota - a systematic review. J Infect. 2019 Dec;79(6):471-489.
    4. Macke L, Schulz C, Koletzko L, Malfertheiner P. Systematic review: the effects of proton pump inhibitors on the microbiome of the digestive tract-evidence from next-generation sequencing studies. Aliment Pharmacol Ther. 2020 Mar;51(5):505-526.
    5. Hojo M, Asahara T, Nagahara A, Takeda T, Matsumoto K, Ueyama H, Matsumoto K, Asaoka D, Takahashi T, Nomoto K, Yamashiro Y, Watanabe S. Gut Microbiota Composition Before and After Use of Proton Pump Inhibitors. Dig Dis Sci. 2018 Nov;63(11):2940-2949.
    6. Bruno G, Zaccari P, Rocco G, et al. Proton pump inhibitors and dysbiosis: Current knowledge and aspects to be clarified. World J Gastroenterol. 2019;25(22):2706-2719. doi:10.3748/wjg.v25.i22.2706
    7. Dong T, Pisegna J. Passing the "Acid Test": Do Proton Pump Inhibitors Affect the Composition of the Microbiome? Dig Dis Sci. 2018 Nov;63(11):2817-2819.
    8. Nista EC, Candelli M, Cremonini F, Cazzato IA, Zocco MA, Franceschi F, Cammarota G, Gasbarrini G, Gasbarrini A. Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial. Aliment Pharmacol Ther. 2004 Nov 15;20(10):1181-8.
    9. Homan M, Orel R. Are probiotics useful in Helicobacter pylori eradication? World J Gastroenterol. 2015 Oct 7;21(37):10644-53.

*Enterogermina KSA 2B capsules SMPC last update May 2014

  • Bacillus Clausii in H-Pylori - 2021

For Pharmacovigilance, Please contact: +966-54-428-4797, ksa_pharmacovigilance@sanofi.com. To report any side effect(s): Saudi Arabia: The National Pharmacovigilance and Drug Safety Centre (NPC). Fax: +966-11-205-7662 • Call NPC at +966-11-203-8222, Exts: 2317, 2356, 2340. • SFDA Call Center: 19999 • E-mail: npc.drug@sfda.gov.sa • Website: www.sfda.gov.sa/npc. To report any Product Technical Complaint, please contact SANOFI Quality Department: Email: quality.greatergulf@sanofi.com. Full Prescribing Information is available upon request: SANOFI, Kingdom of Saudi Arabia, P.O. Box 9874, Jeddah 21423, K.S.A. Tel: +966-12-669-3318, Fax: +966-12-663-6191. For Medical Information, Please contact: +966-12-669-3318, ksa.medicalinformation@sanofi.com. www.sanofi.com.sa

Dosage: children & breast-feeding infants: 1 - 2 vials a day; adults: 2-3 bottles a day or 2-3 capsules a day or 1 sachet a day. Side Effects: There have been reports of allergic reactions (hypersensitivity), including skin rash, urticaria and angioedema. In case of side effects, please contact your physician or pharmacist. Pregnancy and lactation: Enterogermina may be used during pregnancy and lactation. Talk to your doctor or pharmacist before taking this medicine.

MAT-SA-2300030/V1/Jan2023