AUTHOR=Devi T. Barani , Devadas Krishnadas , George Meekha , Gandhimathi A. , Chouhan Deepak , Retnakumar R. J. , Alexander Sneha Mary , Varghese Jijo , Dharmaseelan Sanjai , Chandrika Sivakumar Krishnankutty , Jissa V. T. , Das Bhabatosh , Nair G. Balakrish , Chattopadhyay Santanu 

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

JOURNAL=Frontiers in Microbiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.631140

DOI=10.3389/fmicb.2021.631140

ISSN=1664-302X

ABSTRACT=<p><italic>Helicobacter pylori</italic> 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 <italic>H. pylori</italic>-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 <italic>H. pylori</italic>-associated diseases. However, no specific microbe in the gastric or intestinal microbiota has been clearly linked to <italic>H. pylori</italic> infection and related gastric diseases. Here, we studied <italic>H. pylori</italic> infection, its virulence genes, the intestinal microbiota, and the clinical status of Trivandrum residents (<italic>N</italic> = 375) in southwestern India by standard <italic>H. pylori</italic> culture, PCR genotype, Sanger sequencing, and microbiome analyses using Illumina Miseq and Nanopore GridION. Our analyses revealed that gastric colonization by virulent <italic>H. pylori</italic> strains (<italic>vacAs1i1m1cagA</italic>+) is necessary but not sufficient for developing these diseases. Conversely, distinct microbial pools exist in the lower gut of the <italic>H. pylori</italic>-infected vs. <italic>H. pylori</italic>-non-infected individuals. <italic>Bifidobacterium</italic> (belonging to the phylum Actinobacteria) and <italic>Bacteroides</italic> (belonging to the phylum Bacteroidetes) were present in lower relative abundance for the <italic>H. pylori</italic>+ group than the <italic>H. pylori</italic>- group (<italic>p</italic> &lt; 0.05). On the contrary, for the <italic>H. pylori</italic>+ group, genus <italic>Dialister</italic> (bacteria belonging to the phylum Firmicutes) and genus <italic>Prevotella</italic> (bacteria belonging to the phylum Bacteroidetes) were present in higher abundance compared to the <italic>H. pylori-</italic> group (<italic>p</italic> &lt; 0.05). Notably, those who carried <italic>H. pylori</italic> in the stomach and had developed aggressive gastric diseases also had extremely low relative abundance (<italic>p</italic> &lt; 0.05) of several <italic>Bifidobacterium</italic> species (e.g., <italic>B. adolescentis</italic>, <italic>B. longum</italic>) in the lower gut suggesting a protective role of <italic>Bifidobacterium</italic>. 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.</p>