As a critical component of the tumour immune microenvironment (TIME), the resident microbiota promotes tumorigenesis across a variety of cancer types. Here, we integrated multiple types of omics data, including microbiome, transcriptome, and metabolome data, to investigate the functional role of intratumoral bacteria in gastric cancer (GC). The microbiome was used to categorize GC samples into six subtypes, and patients with a high abundance of Streptococcus or Pseudomonas had a markedly worse prognosis. Further assays revealed that Streptococcus anginosus (SA) promoted tumour cell proliferation and metastasis while suppressing the differentiation and infiltration of CD8⁺ T cells. However, antibiotic treatment significantly suppressed tumorigenesis in SA⁺ mice in vivo. We further demonstrated that the SA arginine pathway increased the abundance of ornithine, which may be a major contributor to reshaping of the TIME. Our findings demonstrated that SA, a novel risk factor, plays significant roles in the initiation and progression of GC, suggesting that SA might be a promising target for the diagnosis and treatment of GC.

Pancreatic cancer is highly malignant, and while fluoropyrimidines (5-fluorouracil [5-FU] and capecitabine) are critical first-line treatments for metastatic cases, drug resistance remains a major challenge. In this study, we identified an association between Citrobacter enrichment in pancreatic tumors and poor overall survival in patients with pancreatic cancer, particularly in patients receiving fluoropyrimidine-based treatment. Co-culture of 5-FU with the Citrobacter freundii strain isolated from pancreatic cancer and intratumoral injection of this strain in xenograft models significantly reduce the antitumor efficacy of 5-FU. Subsequent analyses using mass spectrometry, bioinformatics, and gene knockout experiments revealed that C. freundii strain inactivates 5-FU via the PreTA, which is homologous to human dihydropyrimidine dehydrogenase (DPD). Gimeracil, a DPD inhibitor, preserves the efficacy of 5-FU by blocking PreTA activity. Other preTA-harboring bacteria also metabolized 5-FU, indicating broader bacteria-mediated 5-FU resistance. These findings reveal a potential microbiome-driven mechanism of chemotherapy failure and identify PreTA as a druggable target.

Gastric cancer (GC) is one of the most lethal human malignancies worldwide. Serine metabolism is essential for meeting biosynthetic demands and regulating the redox state of GC cells. This study demonstrates that Skullcapflavone II (SkII) selectively inhibits the proliferation and metastasis of GC cells. Transcriptomic and metabolomic analyses reveal that SkII treatment significantly affects serine metabolism in GC cells, and isotope tracing experiments confirmed that SkII reduces intracellular L‐serine levels by inhibiting uptake rather than de novo synthesis. Furthermore, IHC analysis reveal significant upregulation of the L‐serine transporter SLC1A4 in GC tissues. Binding studies using PELSA, SPR, DARTS, CETSA, and MD suggest that SLC1A4 is a potential direct target of SkII. SkII‐induced disruption of serine metabolism resulted in an imbalance in GSSG/GSH, leading to increased accumulation of intracellular ROS and oxidative stress. This metabolic disruption causes mitochondrial damage, impaired energy production, and increased apoptosis in GC cells. Additionally, in vivo studies reveal that a serine and glycine deficient diet significantly enhanced the antitumor efficacy of SkII, highlighting its potential as a combinatorial therapeutic strategy. These findings provide compelling evidence that SkII is a novel candidate for targeting serine metabolism, suggesting a promising therapeutic approach for treating GC.

The interaction between gut microbiota dysbiosis and CKD progression via the “gut–kidney axis” is increasingly recognized. Gut-derived uremic toxins (e.g., indoxyl sulfate and p-cresyl sulfate) accumulate systemically, while beneficial metabolites like short-chain fatty acids (SCFAs) decrease, contributing to inflammation, oxidative stress, and kidney fibrosis. Traditional Chinese Medicine (TCM), including complex formulae, single herbs, and active ingredients, has long been used to manage CKD. Emerging evidence—primarily from animal studies—highlights its potential to alleviate the disease by modulating the gut microbiota. This review summarizes how TCM interventions re-establish gut microbial symbiosis by regulating microbial composition, reducing toxin load, and reinforcing intestinal barrier integrity, thereby ameliorating systemic inflammation and protecting kidney function. Targeting the gut microbiota represents a promising therapeutic frontier for CKD, and TCM offers a rich resource for developing novel microbiota-modulating strategies. However, future research must focus on validating molecular mechanisms, standardizing TCM preparations, and conducting rigorous clinical trials to facilitate clinical translation.

Prostate cancer is the second most prevalent cancer globally and the fifth leading cause of cancer-related mortality among men. 1 As the cornerstone treatment for advanced prostate cancer, androgen...