## 3 Gastric Cancer
### Gastric Cancer and H. pylori  
Even though _Helicobacter pylori_ infection and its consequences are being extensively studied, its presence is associated with a growing number of diseases. _H. pylori_ has been linked to multiple sclerosis; celiac disease; asthma; anaemia; insulin resistance; diabetes; and, most importantly, gastric cancer [59].  
Although the cycle leading from _H. pylori_ infection to GC development has been well described, little is known about the impact of _H. pylori_ on the composition of the gastric microbiota. Chronic _H. pylori_ infection damages the gastric parietal cells responsible for acid secretion. Higher stomach pH creates a favourable environment for intestinal flora (IF) to develop. Following Hp infection, the microbiota of GC patients was reported to demonstrate higher numbers of _Streptococcus_, _Lactobacillus_, _Veillonella_, and _Prevotella_ than subjects without _H. pylori_ infection (murine model with artificially induced microflora). It has been suggested that IF accelerates Hp-associated GC, however, little is known about the possible mechanism [50]. A study on murine model reported that mice with both [PERSON]'s flora and _H. pylori_ infection exhibited a more severe GC outcome than germ-free mice or mice infected only with _H. pylori_; in addition, a decrease in _Clostridum_ and _Bacteroides_ species with significant a increase in _Lactobacillus murinus_ was reported, suggesting that the presence of IF might enhance the immune response, and thus accelerate the outcome of GC [50]. Similar results were obtained by [PERSON] et al., who reported that GIN (gastrointestinal intraepithelial neoplasia) develops significantly more slowly in germ-free mice or mice with _H. pylori_ association compared with specific pathogen-free _H. pylori_ infected animals. Additionally, [PERSON] et al. reported an increase in _Firmicutes_ with a simultaneous decrease in _Bacteroidetes_ and _Cyanobacteria_ in the stomach of the mice (microbiota composition quantified by pyrosequencing) [60].  
\begin{table}
\begin{tabular}{c c} \hline \hline
**State** & **Bacterial Signatures** \\ \hline Healthy stomach & Proteobacteria, Firmicutes, Actinobacteria, \\  & Bacteroidetes, and Fusobacteria [40] \\  & _Lactobacillus_, _Propinibacterium_[40] \\  & _Enterococcus_, _Streptococcus_, _Staphylococcus_, _Pseudomonas_, _Stomatococcus_[41] \\  & _Clostridium_, _Veillonella_[42] \\ \hline Gastritis & _Helicobacter_, _Neisseria_, _Prevotella_, and _Streptococcus_ \\  & _genera_[44] \\  & _Streptococcus_, _Prevotella_, _Neisseria_, _Haemophilus_, _Porphyomonas_[45] \\ \hline Gastritis & \
\begin{tabular}{c} Proteobacteria (_Xanthomonadaceae_ and \\ _Enterobacteriaceae_, as well as genera such as _Citrobacter_, _Plyllobacterium_, and _Achromobate_), Firmicutes \\ (_Lactobacillus_, _Clostridum_), _Bacteroidetes_, \\ (_Rlodoxoccus_), and Fusobacteria \\ \end{tabular} \\  &
\begin{tabular}{c} Oral bacteria (_Peptostreptococcus_, _Streptococcus_, and _Fusobacterium_) [52] \\ bacteria harbouring nitrosating enzymes [51, 52] \\ \end{tabular} \\ \hline \hline \end{tabular}
\end{table}
Table 3: Bacterial signatures of healthy stomach microbiome as well as gastritis and cancer related stomach microbiota.  
Interestingly, [PERSON] et al. reported that the level of \(H\). _pylori_ decreases significantly in GC-related microbiota and the microbial community was enriched in non-Helicobacter _Proteobacteria_ (r = \(-\)0.59, \(p<0.0001\)), _Firmicutes_ (r = \(-\)0.49, \(p<0.0001\)), _Bacteroidetes_ (r = \(-\)0.43, \(p<0.0001\)), and _Actinobacteria_ (r = \(-\)0.54, \(p<0.0001\)). A study also reported a decrease in \(H\). _pylori_ abundance in GC patients, that the presence of \(H\). _pylori_ was associated with co-colonization by Bacteroidetes and Fusobacteria, and that the GC microbiota was dominated by Proteobacteria [44].