Probiotics Antimicrob Proteins. 2026 Sep 14. doi: 10.1007/s12602-026-11134-3. Online ahead of print.

ABSTRACT

Gastric cancer (GC) remains a major global health burden and is frequently diagnosed at advanced stages owing to the limited sensitivity, invasiveness, and restricted availability of current screening strategies. Increasing evidence indicates that the gastric microbiome including Helicobacter pylori and diverse non-H. pylori bacteria, fungi, and viruses actively contribute to gastric carcinogenesis by modulating mucosal immunity, chronic inflammation, epithelial barrier integrity, and metabolism. High-throughput sequencing has revealed reproducible dysbiosis signatures in GC, characterized by enrichment of taxa such as Lactobacillus, Streptococcus, and Fusobacterium, and depletion of beneficial commensals, including Bifidobacterium and short-chain fatty acid producing anaerobes, some of which show promise as diagnostic or prognostic biomarkers. This review summarizes current knowledge on bacterial, fungal, and viral inhabitants of gastric tumors, highlighting their mechanistic roles in tumor initiation and progression and their potential as microbial indicators of disease. It further evaluates noninvasive and minimally invasive early detection strategies based on fecal and salivary microbiota profiling, urinary extracellular vesicles, and metabolomic fingerprints, alongside multi-omics integration and machine-learning models that combine microbial and host features to improve risk stratification. Finally, the review discusses therapeutic avenues including microbiota modulation, immunotherapy microbiome interactions, and personalized medicine frameworks that incorporate microbial signatures into clinical decision-making, underscoring the need for standardized, multicenter studies to translate gastric microbiome insights into robust tools for early detection and targeted intervention in GC.

PMID:42734869 | DOI:10.1007/s12602-026-11134-3

Front Oncol. 2026 Aug 28;16:1907210. doi: 10.3389/fonc.2026.1907210. eCollection 2026.

ABSTRACT

Clonal evolution in hepatocellular carcinoma (HCC), esophageal squamous cell carcinoma (ESCC), and gastric cancer (GC) reflects the interaction of genetic diversification, cell-state plasticity, and tissue-specific selection. Multi-region and single-cell DNA sequencing resolve truncal and subclonal lineages, whereas single-cell and spatial transcriptomics, proteomics, and serial liquid biopsy characterize cellular states, ecological niches, and temporal dynamics. The three cancers differ in dissemination timing, dominant selective pressures, and biomarker maturity: early seeding is best supported in selected HCC cohorts, ESCC is strongly influenced by field cancerization and epithelial-stromal crosstalk, and GC follows subtype- and ecotype-dependent trajectories. We discuss the assumptions and sampling biases that constrain phylogenetic inference, the causal limits of cross-sectional tumor atlases, clonal hematopoiesis, and the incremental value of broad multi-omics over focused assays. Liquid-biopsy detection of minimal residual disease is prognostic, but treatment benefit from marker-guided intervention remains context dependent. Near-term translation requires standardized, decision-linked assays; adaptive therapy and evolutionary steering remain investigational.

PMID:42729528 | PMC:PMC13563159 | DOI:10.3389/fonc.2026.1907210

Front Pharmacol. 2026 Aug 26;17:1881703. doi: 10.3389/fphar.2026.1881703. eCollection 2026.

ABSTRACT

BACKGROUND: Gastric intestinal metaplasia (GIM) is a typical precancerous lesion of gastric cancer (PLGC). Previous studies have demonstrated that Xinkai Kujiang formula can effectively alleviate GIM, but its underlying mechanism remains largely unclear.

METHODS: The GIM rat model was established using 2% sodium salicylate and 20 mmol/L sodium deoxycholate, and then the rats were treated with Banxia Xiexin Decoction (BXD) and Xinkai Kujiang Decoction (XKD) for 4 weeks. Multi-omics analyses including 16 S ribosomal RNA gene sequencing, transcriptomics, single-cell RNA sequencing, network pharmacology, and component identification were performed to explore the therapeutic mechanisms of Xinkai Kujiang formula on GIM.

RESULTS: In the model rats, severe gastric mucosal atrophy was observed, characterized by disordered glands and goblet cells. Following intervention with BXD and XKD, gastric mucosal thickness was restored, glandular structures became regularly arranged, and the number of metaplastic goblet cells markedly decreased. Microbiota profiling of gastric mucosa revealed significant enrichment of Lactobacillus and Enterococcus in the model group. These abundances were reduced in the BXD group, and short-chain fatty acid-producing bacteria such as Alistipes and Lachnospira were enriched. In the intestine, opportunistic pathogens like Streptococcus and Enterococcus were enriched in the model group, whereas Corynebacterium and Bifidobacterium were enriched in the XKD group. Transcriptomic analysis presented that BXD upregulated innate immune-related genes in the gastric mucosa, and single-cell RNA sequencing (scRNA-Seq) showed that XKD alleviated GIM by inhibiting the VEGF and HIF-1α pathways, reducing angiogenesis, suppressing inflammatory infiltration, and regulating energy metabolism.

CONCLUSION: BXD and XKD improve gastrointestinal microbiota disorders and metabolic disorders, enhance gastric mucosal immunity, and inhibit the VEGF and HIF-1α pathway. Collectively, these multi-omics data provide novel insights into the therapeutic mechanisms of Xinkai Kujiang formula for GIM.

PMID:42718732 | PMC:PMC13553361 | DOI:10.3389/fphar.2026.1881703

Biofactors. 2026 Sep-Oct;52(5):e70150. doi: 10.1002/biof.70150.

ABSTRACT

Gastrointestinal malignancies, including gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic ductal adenocarcinoma, remain major causes of cancer-related morbidity and mortality worldwide. Although chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of hematologic malignancies, its efficacy in gastrointestinal solid tumors remains limited by antigen heterogeneity, insufficient trafficking and infiltration, immunosuppressive tumor microenvironments, on-target off-tumor toxicity, and adaptive resistance. In this review, we summarize the current landscape of CAR-T therapy in gastric cancer, colorectal cancer, hepatocellular carcinoma, and pancreatic cancer, with a focus on representative target antigens and emerging biomarker strategies. We further discuss two major categories of biomarkers: target antigen-related biomarkers and conventional dynamic biomarkers, including serum tumor markers, cytokine changes, CAR-T expansion kinetics, and antigen-loss monitoring. In addition, we highlight how single-cell ribonucleic acid sequencing and spatial transcriptomics provide complementary insights into cellular states, immune exhaustion, stromal barriers, and spatially restricted immune exclusion. By integrating these multi-omics approaches with biomarker-guided patient stratification and next-generation CAR-T engineering, gastrointestinal solid tumor CAR-T therapy may evolve from empirical optimization toward mechanism-driven and precision-guided clinical translation.

PMID:42717494 | PMC:PMC13558850 | DOI:10.1002/biof.70150