## 3 Gastric Cancer
### Microbiota in Gastric Adenocarcinoma  
[PERSON] et al. reported that samples of gastric microflora obtained from gastritis patients tended to be more abundant than those obtained from gastric cancer patients. In addition, the gastric microbiota of GC patients was dominated by intestinal commensals. Study reported that both study groups were dominated by five phyla: Proteobacteria (69.3%), Firmicutes (14.7%), Bacteroidetes (9.0%), Actinobacteria (4.3%), and Fusobacteria (1.3%). GC-related gastric microflora was characterized by decrease in the genera _Helicobacter_, _Fusobacterium_, and _Neisseria_, as well as some members of the Bacteroidetes. The gastric microflora of the GC patients was reported to be enriched in Proteobacteria such as the _Xanthomonadaceae_ and _Enterobacteriaceae_, as well as genera such as _Citrobacter_, _Plyllobacterium_, and _Achromobacter_. In addition, the gastric microbiota of GC patients was enriched in intestinal mucosa commensals, that is, _Lactobacillus_, _Plyllobacterium_, _Clostridium_, and _Rhodococcus_[44]. Similar results were obtained by [PERSON] et al., suggesting that the presence of intestinal microbiota in stomach might be linked to GC development [49, 50]. This research must be also considered carefully, as it was performed on a murine model with artificially induced microflora. It is known that microbiota-related analyses are able to give only a short overview owing to differences in mouse and human gastric tract structure and metabolism, among others. The gastric microbiota of GC patients was shown to be enriched in nitrosating bacteria; such nitrate-reducing activity increases the intragastric concentrations of nitrite and _N_-nitroso compounds, which have been reported to increase the risk of GC development [51, 52].  
Even though _H. pylori_ is the main pathogen increasing the risk of GC, studies reported that gastric colonization by non-_Helicobacter pylori_ bacteria, such as Actinobacteria, Bacteroides, Firmicutes, Fusobacteria, and Proteobacteria, might be related to higher risk of GC development. However, the mechanism by which this microbe can influence the outcome of GC is not clearly understood [44, 49, 53]. Some Bacteroides and Fusobacteria members have been found to exhibit cancer promoting activity. It has been reported that infection with _Bacteroides fragilis_ is directly linked to colorectal cancer development. _B. fragilis_ toxin (BFT) strongly stimulates the immune system and influences epithelial homeostasis through E-cadherin cleavage, leading to extensive cell proliferation [54]. In addition, _B. fragilis_ lipid A has been found to be structurally similar to _H. pylori_ lipid A [55]. It is thus possible that, while translocating from the intestine to the stomach during the development of GC, _B. fragilis_ produces BFT and promotes GC development. _Fusobacterium nucleatum_ has been frequently isolated from stool samples of colorectal cancer (CRC) patients. It has been suggested that the bacterium influences CRC development owing to its ability to induce an inflammatory response (especially stimulation of TNF-a and N Fk-B (nuclear factor kappa B) production) and bind E-cadherin to the epithelial cell [56]. It has also been reported that increased abundance of Proteobacteria is a sign of overall dysbiosis in gut microbiota and has been linked to colitis and colorectal cancer outcome. Studies reveal that impairments in the innate immune system promote the outgrowth of Proteobacteria, and that increases in the Proteobacteria number enhance the immune response in the host gut, leading to colitis development [57, 58]. Table 3 illustrates bacterial signatures of healthy stomach microbiome, as well as gastritis and cancer-related microbiota.