To the Editor: We welcomed with enthusiasm the new ACG/CAG guideline concerning management of dyspepsia, which encompasses evaluation of Helicobacter pylori (HP) infection, endoscopy and pharmacological therapies (1). It is a step forward towards diminishing clinical uncertainty in functional dyspepsia (FD) defined by Rome IV criteria. Duodenal inflammation/impaired mucosal integrity are key players behind FD (2). HP is one of many microbial agents associated with FD. Non-microbial factors (e.g., alcohol/stress) disturb gut–brain axis and contribute to duodenal dysfunction (3). Therefore we put under debate the ACG–CAG recommendation, that dyspepsia patients (DP) under the age of 60 should have a non-invasive test for HP, and therapy for HP infection if positive. First, this recommendation is based mostly on studies focused on comparisons between test and treat (T/T) with prompt upper GI endoscopy based therapies in undiagnosed DP. Not surprisingly, T/T approach resulted in statistically significant cost savings. However antibiotic eradication regimens were not superior to proton pump inhibitors (PPIs) and only trend towards a reduction in cost for HP T/T compared to empirical PPI therapy was found. Trials investigating T/T approach were biased, save studies, where cost reduction of T/T over treatment based on endoscopic result was found (1). As multitude of factors contribute to FD we consider HP T/T as “a bridge too far” approach, at least in countries with high HP infection prevalence rates. HP eradication is associated with only small benefit for symptom control over no eradication (1). The recent systematic review (SR) analyzing 25 RCTs with 5555 patients with FD found the benefit of HP eradication-therapy for symptom improvement during long-term follow up at >1 year (P<0.0001) but not short term follow up <1 year (P=0.27). Seven studies of this SR showed no benefit of HP eradication-therapy on quality of life and eight studies found that HP eradication-therapy increased the likelihood of treatment-related side effects compared to no eradication therapy (4). According to Kyoto consensus at present there are no criteria to predict whether a patient with dyspeptic symptoms will respond to eradication therapy or not (3). The lack of trials investigating both HP-positive and negative patients to antibiotic therapy or placebo, tempt us to speculate that antibiotic therapy per se is the reason for symptoms settlement in dyspepsia.
The clinical implications are important as harsh eradication protocols could be harmful to patients with non-investigated celiac disease or those at risk for clostridium difficile infection. Eradication therapy is associated with antibiotic resistance and might contribute to symptom persistence. As the number of studies comparing different antibiotic protocols is limited, perhaps the choice of antibiotics could include those with least potential for antimicrobial resistance/adverse events. For example rifaximin, in a double blind, placebo controlled, randomized trial has been effective in the relief of global dyspeptic symptoms in DP(5). Moreover, the global adverse effects of antibiotic use are unappreciated. The evidence that loss of microbial diversity contribute to chronic diseases (metabolic/autoimmune/cancer) is strong and need for microbial/biodiversity recovery is high. Non-pharmacological approaches should not be abandoned. The evidence of their efficacy is rising.