Whenever possible and reasonable, standard HP eradication therapy based on PPIs and antibiotics should be carried out. If, however, this is not possible or has failed even after clarification by an antibiogram, a probiotics-supported therapy may well be successful, as the reported cases suggest.
To generate a possible scientific rationale, is worth taking a closer look at the environment in which HP prospers. HP gains its energy by converting urea into ammonia and CO2, with the enzyme urease catalyzing this exothermic reaction. Ammonia provides nitrogen for the synthesis of amino acids and protects HP from the acidic gastric environment. Ammonia, however, also causes the well-known irritation of the gastric mucosa. But the urease produced by HP is a double-edged sword, without which HP has no energy and no nitrogen from the degradation of urea and also no protection at pH values < 4, but if the pH exceeds the critical value of 8.2 it also does not survive. To avoid a pH value > 8.2, HP urease loses its activity at a pH > 6 and gastric acid is required to lower the pH back to levels that allow urease activity [5]. Although a pH between 6 and 8.2 is not immediately fatal for HP, the bacterium cannot survive in this pH range for the long-term because of the lack of energy and nitrogen.
A further argument for an antibiotics-free eradication therapy is provided by a study from 2006, which showed that the stomach is home to a rich microbiome, with numerous species of firmicutes, proteobacteria, bacteroidetes, actinobacteria and fusobacteria [6]. In about 50% of all humans, HP is part of this ecosystem. One can reasonably assume that, as in any intact ecosystem, there is a balance between species, and thus the gastric colonization with HP in most cases does not cause damage. After all, about 80% of all HP infections remain symptom free, which suggests that only a massive disturbance of the gastric ecosystem, for example due to antibiotic administration, disease or an unfavorable lifestyle, causes a pathogenic shift in the balance in favor of HP. From gastric biopsies, 19 species of lactobacilli have been detected [7], which seem to play an important role in the gastric microbial balance and some of them excrete substances that are able to kill HP in their immediate surroundings.
Due to the properties of HP discussed above, its antibiotic-free may be achieved with the following strategies:
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Inactivation of urease to deprive HP of its most important regulator of conditions supportive of survival
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Raising the pH value at the gastric mucosa to > 6
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Add-on therapy with selected lactobacilli
Ad 1) Inactivation of urease is difficult because drugs that have a strong inhibitory, such as hydroxycarbamide [8], are contraindicated due to their toxicity; the same is true for heavy metal ions such as silver, mercury or copper. Natural substances such as boswellic acids from the burseraceous resin or epiberberine from Coptis chinensis, a plant traditionally used in Asia against gastrointestinal discomfort [9], appear more promising. However, there is a lack of strong clinical data on these natural substances.
Ad 2) PPIs are proven, well tolerated low-cost substances, which reduce the production of gastric acid by approx. 80% and thus increase gastric pH to > 6 for a prolonged period of time. Their effectiveness can be further increased by other therapeutics that raise gastric pH, such as H2 blockers (famotidine, ranitidine, etc.) and various carbonates. There is evidence from gastric surgery that PPIs as well as the H2 blocker ranitine are able to increase the gastric pH above 6.0 [10, 11].
Ad 3) Based on the evidence from international studies [12], national and international guidelines recommend the add-on use of lactobacilli in HP eradication therapy [2, 3]. Numerous randomized, controlled trials and meta-analyses have shown that probiotic-supported HP eradication therapies are more effective than those without probiotics in terms of patient adherence, side effects and eradication rates [13, 14]. However, the studies also showed that not all probiotic germs are equally suitable. Each germ therefore has to be studied individually for its suitability as an add-on for HP eradication therapy. In Austria, the germ Lactobacillus casei rhamnosus, strain 35 (LCR 35) is a promising candidate, since it has regulatory approval for the treatment of antibiotic-associated diarrhea and has no known side effects [15]. In vitro its supernatant has demonstrated a bactericidal effect against numerous pathogenic germs including HP [16]. In a non-interventional study, LCR 35 was able to reduce antibiotic side effects and increase eradication rates in a standard HP eradication therapy [17].
Based on these considerations, a combination of PPIs and other substances that increase the gastric pH together with LCR 35 as an add-on could be quite promising, especially since the PPIs raise the pH into a range favorable for lactobacilli.