Multi-Omics Study Reveals the Role of Tumoral Bacteria with Immune Environment in Gastric Carcinogenesis

Recently, byThe Fifth Affiliated Hospital of Zhengzhou University, Xbiome, Xellar BiosystemsThe joint research team, published in an internationally renowned journalGenomics, Proteomics & Bioinformatics(GPB, with an average impact factor of 9.1 over five years, JCR Q1 zone) published the latest collaborative research findings.

Gastric cancer (GC) is a multifactorial disease, with causes involving genetic background, dietary habits, immune function, chronic gastritis, and other factors. The 5-year survival rate for patients is only about 25%, and if peritoneal metastasis occurs, the survival rate drops to less than 5%. Existing studies have found,Specific bacteria within tumor tissues (intratumoral bacteria) are significantly associated with carcinogenesis.Some of these pathogens have been proven to be pro-cancer factors in various cancers, including stomach cancer. At the same time, the tumor microenvironment, with weakened immune surveillance and enriched nutrients, also provides an ideal "habitat" for the colonization of specific bacteria. Therefore,In-depth research on the function of intratumoral bacteria and their interaction mechanisms with the microenvironment is of great significance for developing targeted treatment strategies and constructing anti-cancer engineered strains.

In the study published this time, the research team adopted a multi-omics integration strategy involving microbiome, metabolome, and proteome to systematically analyze tumor/non-tumor paired samples from gastric cancer patients. First, to investigate the composition of intratumoral microbiota in different gastric tumor microenvironments, the researchers performed third-generation high-throughput sequencing based on full-length 16S rRNA for cancer tissue, adjacent tissue, and non-cancerous tissue samples. To validate and characterize the differences in microbiota across various samples, the researchers also conducted a meta-analysis using six public datasets to extract more robust microbial signals. The study found that bacterial diversity within gastric cancer tumor tissues was significantly higher than in adjacent and healthy tissues. Notably, bacteria such as Lactobacillus and Prevotella were markedly increased in tumor tissues, while Helicobacter pylori (Hp), a recognized risk factor for gastric cancer, was more enriched in adjacent and non-cancerous tissues.This suggests that the tumor microenvironment may "select" specific microbial communities.

Due to the differences in bacterial composition between tumor and non-tumor tissues, and the distinct metabolic states of these tissues, the research team further examined the metabolic and proteomic information of these tissues using mass spectrometry. The results showed that, compared with other tissues,The metabolite kynurenine is significantly enriched in tumor tissues. Previous studies have found that kynurenine is associated with immunosuppression, and its accumulation may help tumors evade attacks from the immune system.In terms of proteins, the researchers identified a total of 39 proteins related to host immunity, particularly those enriched in the tryptophan metabolism pathway in tumor tissues. Through further in-depth functional analysis of the differential proteins between groups and metabolic pathway network mapping, the researchers proposed the following hypothesis:Differences in bacterial communities between tumor and non-tumor tissues may influence tryptophan metabolism in the host immune system, leading to changes in related metabolites, which could be associated with tumor initiation and progression.

Subsequently, the research team integrated various omics data to construct a complex regulatory network, identifying potential relationships between intratumoral microbiota, proteins, and metabolites in gastric cancer. For instance, certain bacteria enriched in tumors (such as Brevundimonas nasdae, Brevundimonas vesicularis, Bacteroides thetaiotaomicron) were associated with elevated kynurenine levels and the expression of immunosuppressive proteins. In contrast, Helicobacter pylori was linked to an increase in regulatory T cells (Tregs).These provide a theoretical basis for the development of new biomarkers and therapeutic targets.

The success of this research is due to the deep integration of the core advantages of the three parties, among which,Marshall Medical Research Center, Fifth Affiliated Hospital of Zhengzhou UniversityWith its profound clinical experience and scientific research strength in the field of gastric cancer, it has provided a solid medical foundation for the research;Xbiomehas contributed its massive proprietary data and cutting-edge research accumulation in the field of human symbiotic microbiota, precisely identifying the research direction, andXellar BiosystemsThey jointly undertook the crucial multi-omics analysis of clinical data, with the latter leveraging its robust bioinformatics capabilities to transform complex biological data into profound insights.

This achievement not only deepens the scientific community's understanding of the microbial etiology of gastric cancer, but alsoProvided important theoretical basis and translational directions for researchers and enterprises in the global microbial pharmaceuticals field to screen functional strains with therapeutic potential and develop innovative diagnosis and treatment solutions for gastric cancer.

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