Gastric Cancer Microbiome

Abstract

Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. <i>H. pylori</i> remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-<i>H. pylori</i> microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the <i>H. pylori</i> protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, <i>Helicobacter</i> and <i>Prevotella</i> figured in the “top 6” genera of every group. <i>Helicobacter</i> was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while <i>Prevotella</i> was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk.

Microbiota and the Immune System—Actors in the Gastric Cancer Story

“…Another example of a microorganism involved in the pathogenesis of GC is the genus Prevotella . These anaerobic gram-negative pleomorphic rods have been detected as one of the dominant species in GC patient samples [ 124 , 125 , 126 ]. More specifically, there are two representatives of this type: Prevotella acnes and Prevotella copri .…”

Peptic Ulcer and Gastric Cancer: Is It All in the Complex Host–Microbiome Interplay That Is Encoded in the Genomes of “Us” and “Them”?

“…However, in direct contrast, long-term H. pylori infection leads to hypochlorhydria due to decreased H + secretion by the parietal cells and this allows the growth of several other bacteria (discussed later) ( McColl et al, 1998 ). This cascade of events leads to atrophic gastritis, which eventually progresses to intestinal metaplasia, intraepithelial neoplasia, and GC ( Barra et al, 2021 ).…”

“…On the other hand, GC patients from China had enrichment of species such as Slackia exigua, Streptococcus anginosus, Peptostreptococcus stomatis, Dialister pneumosintes , and Parvimonas micra in the stomach ( Coker et al, 2018 ). Furthermore, an overgrowth of nitrate-reducing bacteria in the atrophic stomach is attributed to the development of gastric cancer via the accumulation of N-nitroso compounds ( Barra et al, 2021 ).…”

Helicobacter pylori-Induced Inflammation: Possible Factors Modulating the Risk of Gastric Cancer

“…Higher metabolites produced by dysbiosis of the gut microbiome, such as N-nitroso compounds and lactate, are thought to affect the immunological response as well as DNA damage, resulting in gastric carcinogenesis [ 75 , 76 ]. Recent studies proved that gut microbiota plays a significant role in the progression of gastric inflammation, AG, and IM after H. pylori eradication [ 77 , 78 ]. However, retrospective and only association-based findings are the limitations of these studies.…”