Adjunctive Oral Treatment Improves Helicobacter pylori Eradication Without Evidence of a Dose-Response Gradient: An Updated Meta-Analysis Challenging the Oral Reservoir Hypothesis

Abstract

Standard antibiotic regimens for Helicobacter pylori are failing more often as resistance rises, and the oral cavity has long been proposed as an extragastric reservoir that seeds gastric recolonization.If so, treating the mouth should improve gastric eradication, a testable clinical claim rather than a correlation.We therefore pooled the randomized evidence on adjunctive periodontal and oral hygiene treatment identified through our search strategy and tested the reservoir hypothesis rather than assuming it.We included randomized and quasi-randomized controlled trials in which adults or children receiving standard eradication therapy for confirmed gastric H. pylori infection were allocated to receive, or not receive, an adjunctive periodontal or oral hygiene intervention.Trials were identified by citation searching of three previous syntheses and by targeted searches for trials published after August 2015, without language restriction.The primary outcome was eradication confirmed at the first post-treatment assessment, at least four weeks after therapy; the co-primary outcome was absence of recurrence at six months or later.We pooled odds ratios and risk ratios using random-effects models with the Hartung-Knapp adjustment, assessed risk of bias with the second version of the Cochrane risk-of-bias tool, and rated certainty using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach.Subgroup analyses by intervention intensity, region, publication period, and source verifiability were prespecified, and small-study effects were examined by funnel plot, Egger and Begg tests, and trimand-fill.Eleven trials contributed data.For eradication, 10 trials, including 1,575 participants, gave a pooled odds ratio of 2.84 (95% confidence interval 1.84 to 4.39; p = 0.0004) with modest heterogeneity (I-squared 34.4%, prediction interval 1.18 to 6.87), corresponding to eradication in 87.1% versus 72.0% and a number needed to treat of six.For recurrence, four trials including 999 participants gave a pooled odds ratio for remaining free of infection of 4.64 (95% confidence interval 2.06 to 10.45); the same trials pooled as risk ratios gave 1.63 (95% confidence interval 0.86 to 3.09), and both are reported with equal prominence because the finding does not survive the change of scale.There was no evidence of small-study effects (Egger p = 0.51; none imputed by trim-and-fill).No gradient with intervention intensity was detected: an antiseptic mouthrinse alone performed at least as well as full-mouth scaling and root planing (test for subgroup differences p = 0.19), although the stratum-level confidence intervals were wide, and the largest single effect in the dataset came from a placebo-controlled trial of an antiseptic mouthrinse with no mechanical component.No trial was at low overall risk of bias.Adjunctive oral treatment is consistently associated with better eradication, but no evidence of a doseresponse gradient was detected, which does not support simple mechanical removal of an oral reservoir as the explanation.Certainty was moderate for eradication, downgraded for risk of bias, and low for recurrence, downgraded for risk of bias and imprecision.