**5. Interrelations between** *H. pylori* **and other gastric microbiota**

Numerous studies have shown significant variability of the gastric microbial communities with respect to *H. pylori* status. One such study was carried out by Osaki et al. [37], who examined the gastric microbiota of *H. pylori*-positive and *H. pylori*-negative Mongolian gerbils. The study showed a larger number of *Bifidobacterium* spp*.* in *H. pylori*-positive gerbils, compared to the *H. pylori*negative, while *Eubacterium cylindroides* and *Prevotella* spp*.* were only found in the *H. pylori*-negative group.

Several mouse model studies have also shown clear differences in the composition of the gastric microbiota with respect to *H. pylori* status. Infection by *H. pylori* of pathogen-free female BALB/c mice has been shown to reduce the *Lactobacillus* spp*.* in the gastric microflora [26]. In transgenic, insulin-gastrin (INS-GAS) mice, the *H. pylori*-infected male mice show a significantly different phyla compared to the non-infected control group, with an increase in *Firmicutes* and a decrease in *Bacteroidetes* [26]. Findings in *H. pylori*-colonized C57BL/6 N female mice included reductions in *Firmicutes* (class *Bacilli*), *Bacteroidetes*, and *Proteobacteria* and an increase of *Firmicutes* (class *Clostridia*), *Proteobacteria* (genus *Helicobacter*), and *Verrucomicrobia*. However, other published data on the murine gastric microbiota suggest that neither acute nor chronic *H. pylori* infection substantially modifies the gastric microbial ecosystem [38].

A few studies have also examined *H. pylori*-related microbial differences in humans. One study found relative abundances of *Proteobacteria*, *Spirochetes*, and *Acidobacteria* in *H. pylori*-positive patients, compared to the control *H. pylori*-negative group. Another study demonstrated that patients positive for *H. pylori* culture showed significantly increased colonization of *Proteobacteria* and a decrease in *Actinobacteria* [39].

A few studies have given insight on how other microbial species can affect *H. pylori* by modulating *H. pylori*-induced gastric inflammatory responses. Two studies have

**57**

*Gastric Microbiota: Between Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.86926*

**6. Factors affecting the gastric microbiota**

**6.1 Gastric acidity**

**6.2 Dietary habits**

indicated that the presence of intestinal *Helicobacter* (*H. bilis*, *H. hepaticus*, and *H. muridarum*) can both increase and decrease the severity of *H. pylori*-induced gastric inflammation by altering Treg cell responses [40, 41]. Another study demonstrated that *H. pylori* is present within the intestine in a coccoid form and that its interaction with phagocytes within the intestinal Peyer's patches modifies the intensity of *H. pylori*induced gastritis [42]. However, other studies have shown that the gastric microbiota can accelerate gastric cancer progression in the presence of *H. pylori* and does so with no

differences detected in the composition of the intestinal microbiota [27, 32].

As previously described *H. pylori* infection is associated with a multitude of changes in the gastric physiology and immunology, e.g., reduced gastric acidity, disturbed nutrient availability, and local inflammatory responses. These changes might be one explanation for the shift in the gastric microbial communities described, but the relation between *H. pylori* and non-*H. pylori* microbiota seems to be far more complex and remains to be further clarified. One problem is that so far, most studies are focused only on the effects of *H. pylori* on other microbiota, but little is known of how *H. pylori* is affected by other resident bacteria. Another problem is that different studies cannot be objectively compared, since they highly vary in methods and models used and the results depend on numerous other factors such as the time of *H. pylori* infection and the degree of mucosal inflammation. Therefore, further experiments are needed to give a more extensive understanding of these complex microbial interrelations.

As described, *H. pylori* is the most significant species that colonizes the stomach and a key factor for the gastric microbial diversity but is far from sufficient to provide a wholesome understanding of the factors that determine its dynamics. Major factors that influence and define the dynamics of the gastric microbiota include gastric acidity, inflammation of the gastric mucosa, dietary habits, and use of medications.

The human gastric juice has an interprandial pH of between 1 and 2 in the gastric

lumen, whereas with food ingestion it can reach up to pH 5. pH also varies in the different anatomical regions of the stomach, with most acidic being the fundus and the least being the antrum. The mucus lining the gastric mucosa establishes also a pH gradient from the lumen to the surface of the epithelium. This mucus consists of two sublayers—an inner mucus layer that is firmly attached to the epithelium and a variable mucus layer directly interacting with the lumen [7, 8]. Thus, across the mucus layer, the pH ranges from about 5.5 to 6.8 or even 7 at the surface of the gastric epithelial cells [5, 6]. It was already discussed that the low pH, caused by the hydrochloric acid, restricts the quantity of microorganisms and reduces the risk of infection by pathogens. Hence, sites with higher pH are significantly more hospitable to colonization and have a higher microbial density. Considerable fluctuations in the microbial density have been described with respect to the pH in the stomach, whereby both the quantity and the proportion of genera also fluctuate [43, 44]. Bacteria and bacterial DNA, which are isolated from gastric juice, differ from bacterial isolates adhering to

the mucosa. During abnormal conditions, this balance may be different.

While many studies document the effects of diet on the gut microbiota composition in humans, [45–49] there are only a few, mainly animal model studies,

*Gastric Microbiota: Between Health and Disease DOI: http://dx.doi.org/10.5772/intechopen.86926*

*Gastrointestinal Stomas*

• Traditional or sequence-aided community fingerprinting [28]

• Terminal restriction fragment length polymorphism (T-RFLP) [30]

In an extensive review of eight culture-independent studies, Sheh A. and Fox J. concluded that the most prominent phyla in the stomach are *Proteobacteria*, *Firmicutes*, *Bacteroidetes*, *Actinobacteria*, and *Fusobacteria* [33]. Furthermore, the most abundant phyla in *H. pylori*-positive subjects are *Proteobacteria*, *Firmicutes*, and *Actinobacteria*. In the absence of *H. pylori*, the most abundant phyla are *Firmicutes*, *Bacteroidetes*, and *Actinobacteria*. However, *H. pylori* remains the most dominant species in the stomach, comprising 72–99% of sequencing reads [10, 34]. In the absence of *H. pylori*, analysis consistently shows the presence of *Streptococcus* spp., which seem to be the most abundant genus in *H. pylori*-negative subjects [3, 30, 35, 36]. In the gastric microbiota, the non-*Helicobacter* genera commonly

• Temperature gradient gel electrophoresis (TGGE) [29]

detected are *Streptococcus*, *Prevotella*, *Veillonella*, and *Rothia.*

**5. Interrelations between** *H. pylori* **and other gastric microbiota**

Numerous studies have shown significant variability of the gastric microbial communities with respect to *H. pylori* status. One such study was carried out by Osaki et al. [37], who examined the gastric microbiota of *H. pylori*-positive and *H. pylori*-negative Mongolian gerbils. The study showed a larger number of *Bifidobacterium* spp*.* in *H. pylori*-positive gerbils, compared to the *H. pylori*negative, while *Eubacterium cylindroides* and *Prevotella* spp*.* were only found in the

Several mouse model studies have also shown clear differences in the composition of the gastric microbiota with respect to *H. pylori* status. Infection by *H. pylori* of pathogen-free female BALB/c mice has been shown to reduce the *Lactobacillus* spp*.* in the gastric microflora [26]. In transgenic, insulin-gastrin (INS-GAS) mice, the *H. pylori*-infected male mice show a significantly different phyla compared to the non-infected control group, with an increase in *Firmicutes* and a decrease in *Bacteroidetes* [26]. Findings in *H. pylori*-colonized C57BL/6 N female mice included reductions in *Firmicutes* (class *Bacilli*), *Bacteroidetes*, and *Proteobacteria* and an increase of *Firmicutes* (class *Clostridia*), *Proteobacteria* (genus *Helicobacter*), and *Verrucomicrobia*. However, other published data on the murine gastric microbiota suggest that neither acute nor chronic *H. pylori* infection substantially modifies the

A few studies have also examined *H. pylori*-related microbial differences in humans. One study found relative abundances of *Proteobacteria*, *Spirochetes*, and *Acidobacteria* in *H. pylori*-positive patients, compared to the control *H. pylori*-negative group. Another study demonstrated that patients positive for *H. pylori* culture showed significantly increased colonization of *Proteobacteria* and a decrease in *Actinobacteria* [39].

A few studies have given insight on how other microbial species can affect *H. pylori* by modulating *H. pylori*-induced gastric inflammatory responses. Two studies have

• Sequencing of cloned 16S rDNA [29]

• Next-generation sequencing (NGS) [32]

• Microarrays (PhyloChip) [31]

*H. pylori*-negative group.

gastric microbial ecosystem [38].

**56**

indicated that the presence of intestinal *Helicobacter* (*H. bilis*, *H. hepaticus*, and *H. muridarum*) can both increase and decrease the severity of *H. pylori*-induced gastric inflammation by altering Treg cell responses [40, 41]. Another study demonstrated that *H. pylori* is present within the intestine in a coccoid form and that its interaction with phagocytes within the intestinal Peyer's patches modifies the intensity of *H. pylori*induced gastritis [42]. However, other studies have shown that the gastric microbiota can accelerate gastric cancer progression in the presence of *H. pylori* and does so with no differences detected in the composition of the intestinal microbiota [27, 32].

As previously described *H. pylori* infection is associated with a multitude of changes in the gastric physiology and immunology, e.g., reduced gastric acidity, disturbed nutrient availability, and local inflammatory responses. These changes might be one explanation for the shift in the gastric microbial communities described, but the relation between *H. pylori* and non-*H. pylori* microbiota seems to be far more complex and remains to be further clarified. One problem is that so far, most studies are focused only on the effects of *H. pylori* on other microbiota, but little is known of how *H. pylori* is affected by other resident bacteria. Another problem is that different studies cannot be objectively compared, since they highly vary in methods and models used and the results depend on numerous other factors such as the time of *H. pylori* infection and the degree of mucosal inflammation. Therefore, further experiments are needed to give a more extensive understanding of these complex microbial interrelations.
