Low Bifidobacterium Abundance in the Lower Gut Microbiota Is Associated With Helicobacter pylori -Related Gastric Ulcer and Gastric Cancer

infection in stomach leads to gastric cancer, gastric ulcer, and duodenal ulcer. More than 1 million people die each year due to these diseases, but why most -infected individuals remain asymptomatic while a certain proportion develops such severe gastric diseases remained an enigma. Several studies indicated that gastric and intestinal microbiota may play a critical role in the development of the -associated diseases. However, no specific microbe in the gastric or intestinal microbiota has been clearly linked to infection and related gastric diseases. Here, we studied infection, its virulence genes, the intestinal microbiota, and the clinical status of Trivandrum residents ( = 375) in southwestern India by standard culture, PCR genotype, Sanger sequencing, and microbiome analyses using Illumina Miseq and Nanopore GridION. Our analyses revealed that gastric colonization by virulent strains ( +) is necessary but not sufficient for developing these diseases. Conversely, distinct microbial pools exist in the lower gut of the -infected vs. -non-infected individuals. (belonging to the phylum Actinobacteria) and (belonging to the phylum Bacteroidetes) were present in lower relative abundance for the + group than the - group ( < 0.05). On the contrary, for the + group, genus (bacteria belonging to the phylum Firmicutes) and genus (bacteria belonging to the phylum Bacteroidetes) were present in higher abundance compared to the group ( < 0.05). Notably, those who carried in the stomach and had developed aggressive gastric diseases also had extremely low relative abundance ( < 0.05) of several species (e.g., , ) in the lower gut suggesting a protective role of . Our results show the link between lower gastrointestinal microbes and upper gastrointestinal diseases. Moreover, the results are important for developing effective probiotic and early prognosis of severe gastric diseases.