Background:Helicobacter pylori(H. pylori) is significantly linked to various diseases that seriously impact human health, such as gastric ulcers, chronic gastritis and gastric adenocarcinoma. Methods: The compositional shifts in bacterial communities of the orointestinal axis were surveyed pre/post-eradication ofH. pylori. In total, 60 samples, including stool and salivary specimens, were collected from 15H. pylori-positive individuals (HPP) before beginning and 2 months after receiving the eradication therapy. The V3-V4 regions of the 16S rRNA gene were sequenced using MiSeq. Results: Overall, oral microbiomes were collectively more diverse than the gut microbiomes (Kruskal–Wallis;p= 3.69 × 10−5). Notably, the eradication ofH. pyloriwas associated with a significant reduction in the bacterial diversity along the orointestinal axis (Wilcoxon rank sum test;p= 6.38 × 10−3). Interestingly, the oral microbiome of HPP showed a positive correlation betweenProteobacteriaandFusobacteria,in addition to a significant predominance ofStreptococcus, in addition toEubacterium_eligens, Haemophilus, Ruminococcaceae, ActinomycesandStaphylococcus. On the other hand,Fusobacterium, Veillonella, Catenibacterium, Neisseria and Prevotellawere significantly enriched upon eradicationof H. pylori. Generally,BacteroidetesandFusobacteriapositively coexisted duringH. pyloriinfection along the orointestinal axis (r= 0.67;p= 0.0006). The eradication ofH. pyloriwas positively linked to two distinctive orotypes (O3 and O4). Orotype O4 was characterized by a robust abundance ofVeillonellaandFusobacteria. The gut microbiomes duringH. pyloriinfection showed a remarkable predominance ofClostridium_sensu_stricto_1 and Escherichia_Shigella. Likewise,BifidobacteriumandFaecalibacteriumwere significantly enriched upon eradication ofH. pylori. Conclusions: Finally, the impact of eradication therapy clearly existed on the representation of certain genera, especially in the oral microbiome, which requires particular concern in order to counteract and limit their subsequent threats.