Bacterial therapy to help eradicate Helicobacter pylori and to reduce the gastrointestinal side effects of antibiotics: a possible treatment scheme?

Bacterial therapy to help eradicate Helicobacter pylori and to reduce the gastrointestinal side effects of antibiotics: a possible treatment scheme?

Francesco Di Pierro

Schermata 2018-01-19 alle 12.18.00Helicobacter pylori (Fig. 1), previously called Campylobacter pylori, is a gram-negative, microaerophilic bacterium found usually in the stomach. It was identified in 1982 by two Australian who found it in a patient with chronic gastritis and gastric ulcers, conditions not previously thought to have a bacterial aetiology. H. pylori is also linked to the development of duodenal ulcers and stomach cancer. It is present in the stomach of 50% of the world’s population and asymptomatic in over 80% of those infected. The standard first-line therapy to eradicate H. pylori, is the so-called triple therapy consisting of proton pump inhibitors (PPI), mainly omeprazole, along with the antibiotics clarithromycin and amoxicillin. Variations on the triple therapy have been developed over the years, using a different PPI, or replacing amoxicillin with metronidazole for those with an allergy to penicillin. Due to antibiotic-resistant bacteria, an additional round of antibiotic therapy, the quadruple therapy, consisting of a PPI, a bismuth colloid, metronidazole and tetracyclines, has been developed. Triple therapy is ineffective in 15%–30% of cases and quadruple therapy in 10%–25% of cases [1]. Therapy also often causes side effects such as antibiotic-induced diarrhoea [2]. Recently meta-analysis involving a pediatric population including 29 trials (3122 participants) and involving 17 probiotic regimens was published. Compared with placebo, probiotic-supplemented PPI and antibiotic therapy significantly increased H. pylori eradication rates and reduced the incidence of side effects [3].
Similarly, 13 randomized controlled trials involving 2306 of adult patients were recently included in another meta-analysis. These authors also reported that probiotic supplementation during H. pylori treatment may be effective for improving eradication rates, minimizing the incidence of therapy-related adverse events and alleviating most disease-related clinical symptoms [4].
One of the most investigated probiotics is Bifidobacterium animalis subspecies lactis BB12 (DSM 15954, hereafter referred to as BB12). Reported to reduce episodes of antibiotic-induced diarrhoea during anti-Helicobacter treatment by 60% [5], BB12 increased the eradication rate of H. pylori by 13% in the case of triple therapy, and by 14% in case of quadruple therapy [6,7], and decreased H. pylori urease activity after 6 weeks of therapy [8].
Helicobacter pylori uses molecular hydrogen as a respiratory substrate when grown in the laboratory. It is also known that hydrogen is available in the gastric mucosa and that its use greatly increases stomach colonization by H. pylori. Therefore, hydrogen present in animals as a consequence of normal colonic flora acitivity can facilitate the maintenance of a pathogenic bacterium [9].
Schermata 2018-01-19 alle 12.18.09The strongest hydrogen-producing organisms, are thought to be Escherichia coli, Clostridium, and Enterobacter species [10]; BB12 increased the numbers of stool bifidobacteria and suppressed coliform bacteria (Escherichia, Clostridium, Enterobacter) [11]. Therefore, since colonic bifidobacteria decrease colonic hydrogen production, BB12 might alter hydrogen production and can lessen the severity of H. pylori infection. Another strain has recently been shown to preserve the growth of bifidobacteria thus reducing of the number of opportunistic microorganisms: Enterococcus faecium L3 (LMG P-27496, hereafter referred to as L3) [12], which inhibits H. pylori growth in vitro (Fig. 2). On this basis, BB12 and L3 might be able to be used to better eradicate the gastric pathogen while reducing the number of side effects. The pre-antibiotic use of probiotics likely reduces the severity and/or the length of antibiotic-induced diarrhoea (by increasing the bacterial load), while their use following antibiotic administration likely increases the eradication rate (as they act on a pathogen already reduced in terms of vitality and strength). Thus, a possible treatment approach could be to use probiotics as add-on therapy in order to achieve better eradication of H. pylori while minimizing the gastrointestinal side effects of antibiotic use (Fig. 3).

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1. Malfertheiner P, Bazzoli F, Delchier JC, Celiñski K et al (2011) Pylera Study Group. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet 377(9769):905–913
2. Kwon SB, Lee KL, Kim JS, Lee JK et al (2010) Antibiotics-associated diarrhea and other gastrointestinal abnormal responses regarding Helicobacter pylori eradication. Korean J Gastroenterol 56(4):229–235
3. Feng JR, Wang F, Qiu X, McFarland LV et al (2017) Efficacy and safety of probiotic-supplemented triple therapy for eradication of Helicobacter pylori in children: a systematic review and network meta-analysis. Eur J Clin Pharmacol 73(10):1199–1208
4. Lü M, Yu S, Deng J, Yan Q, Yang C, Xia G, Zhou X (2016) Efficacy of Probiotic supplementation therapy for Helicobacter pylori eradication: a meta-analysis of randomized controlled trials. PLoS One 11(10):e0163743
5. de Vrese M, Kristen H, Rautenberg P, Laue C, Schrezenmeir J (2011) Probiotic lactobacilli and bifidobacteria in a fermented milk product with added fruit preparation reduce antibiotic associated diarrhea and Helicobacter pyloriactivity.JDairyRes78(4):396–403
6. Sheu BS, Wu JJ, Lo CY, Wu HW, Chen JH, Lin YS, Lin MD (2002) Impact of supplement with Lactobacillus- and Bifidobacterium-containing yogurt on triple therapy for Helicobacter pylori eradication. Aliment Pharmacol Ther 16(9):1669–1675
7. Sheu BS, Cheng HC, Kao AW, Wang ST, Yang YJ, Yang HB, Wu JJ (2006) Pretreatment with Lactobacillus- and Bifidobacterium-containing yogurt can improve the efficacy of quadruple therapy in eradicating residual Helicobacter pylori infection after failed triple therapy. Am J Clin Nutr 83(4):864–869
8. Wang KY, Li SN, Liu CS, Perng DS, Su YC, Wu DC, Jan CM, Lai CH, Wang TN, Wang WM (2004) Effects of ingesting Lactobacillus- and Bifidobacterium-containing yogurt in subjects with colonized Helicobacter pylori. Am J Clin Nutr 80(3):737–741
9. Olson JW, Maier RJ (2002) Molecular hydrogen as an energy source for Helicobacter pylori. Science 298(5599):1788–1790
10. Goyal Y, Kumar M, Gayen K (2013) Metabolic engineering for enhanced hydrogen production: a review. Can J Microbiol 59(2):59-78
11. Chen RM, Wu JJ, Lee SC, Huang AH, Wu HM (1999) Increase of intestinal Bifidobacterium and suppression of coliform bacteria with short-term AB ingestion. J Dairy Sci 82(11):2308–2314
12. Lo Skiavo LA, Gonchar NV, Fedorova MS, Suvorov AN (2013) Dynamics of contamination and persistence of Clostridium difficile in intestinal microbiota in newborn infants during antibiotic therapy and use of probiotic strain Enterococcus faecium L3. Antibiot Khimioter 58(11–12):13–18

by Cec Editore