Mostly as a significance of the belief that, ‘the stomach is a sterile organ’due to acid production, unfriendly to bacteria Study on stomach microbiota left inactive for many years,. In addition, the reﬂux of bile acids in the stomach, the thickness of the mucus layer and the eﬀectiveness of gastric peristalsis might have impeded bacterial colonization of the stomach. Furthermore, the nitrate contained in saliva and food is converted by Lactobacilli present in the mouth into nitrite that, once in the stomach, is transformed by gas- tric juice into nitric oxide, a strong antimicrobial agent. All these factors, together with technical diﬃculties in collecting samples for analysis, and the lack of simple, reliable diagnostic tests have hampered the challenging study of the gastric microbiota6. In 1982, Robin Warren and Barry Marshel discovered Campylobacter pyloridis that removed sterile stomach’s dogma. In 1984 the bacterium campylobacter pyloridis termed as H. pylori. H. pylori use complex bacterial mechanisms by inhabiting and colonizing the gastric mucosa and in terms damages it. Therefore, urease that is formed due to production of ammonia from urea, H. pylori hinders gastric elimination. Ammonia helps bacterium to invade the mucus layer by neutralizing acid. After invading mucus layer, bacterium inhabit epithelium and in turns activates the complex inflammatory response, therefore harms the gastric mucosa that results in chronic gastric in effected people, whereas in less than 1% results in gastric malignancies and peptic ulcer in about 10% people.
In 1981, a few months before the discovery of H. pylori, The Lancet reported that a large number of acid-resistant bacterial strains are detectable in the stomach, among which are Streptococcus, Neisseria and Lactobacillus. The presence of these bacteria is not surprising, as the stomach is exposed to swelling of bacteria from the oral cavity and reﬂux of bacteria from the duodenum. More than 65% of phylotypes identiﬁed in the stomach have been described in speci- mens from the human mouth.8 Thus, such species of bacteria as Veillonella, Lactobacillus and Clostridium, that are found in gastric juice may just be transient.9 Transient bacteria establish small colonies for brief periods of time, without colonizing the gastric mucosa, and do not cross talk with the host; however, whether bacteria other than H. pylori colonize the gastric mucosa and cross-talk with the host by penetrating the thick mucus layer, is not known. Thus, the study of the gastric juice alone for the presence of bacteria is not conclusive, and it may underestimate the real pres- ence of bacteria at the mucosal level. Indeed, while
Firmicutes, Bacteroidetes and Actinobacteria dominate the gastric ﬂuid samples, Firmicutes and Proteobacteria are the most abundant phyla in gastric mucosal sam- ples.10Recently, the develop- ment of culture-independent molecular methods based on 16S rRNA genes, such as ﬂuorescent in situ hybrid- ization, dot-blot hybridization with rRNA-targeted probes, denaturing gradient gel electrophoresis, tem- perature gradient gel electrophoresis, and cloning and sequencing of rDNA have facilitated the identiﬁcation and classiﬁcation of gastrointestinal bacteria.13Bik et al.10 analyzed for the ﬁrst time the gastric mucosa of 23 healthy adult subjects using a small sub- unit 16S rDNA clone library approach: They identiﬁed 1056 non-H. pylori clones, 127 phylotypes and ﬁve dominant genera (Streptococcus, Prevotella, Rothia, Fusobacterium and Veillonella). A few years later, Li et al.14 analyzed the gastric microbiota of 10 healthy subjects, by cloning and sequencing 16S rRNA, and identiﬁed 1223 non-H. pylori clones, 133 phylotypes and ﬁve dominant genera (Streptococcus, Prevotella, Neisseriae, Haemophilus and Porphyromonas). In 2013, Engstrand et al.15 investigated the gastric micro- biota of 13 healthy subjects by pyrosequencing, iden- tifying 200 phylotypes and ﬁve dominant genera (Prevotella, Streptococcus, Veillonella, Rothia, Pasturellaceae), and they did not diﬀer by comparing antrum versus body. In the same year, Delgado et al.16 analyzed gastric juice and gastric biopsy samples of 12 healthy subjects by culturing and pyrosequencing, and found that the most abundant genera were Streptococcus, Propionibacterium and Lactobacillus. Although these studies examined diﬀerent populations (African- American, Hispanic, Chinese and European subjects), the gastric microbiota at both the phyla and genera level, was surprisingly similar in all of them, even if with a large degree of inter-subject variability.