Gastric microbiota-mediated immune remodelling in gastric cancer

Increasing evidence indicates that the gastric microbiota plays crucial roles in regulating the tumour microenvironment (TME), influencing gastric tumourigenesis and progression. Several bacteria, including Streptococcus, Lactobacillus and Bacteroides, have shown robust immunomodulatory effects on TME. In this review, we summarise current understanding of the crosstalk between the gastric microbiota and TME in gastric cancer (GC). Functional alterations of the gastric microbiota from healthy mucosa to malignancy are delineated, with emphasis on the impacts of bacteria on different immune cell populations in gastric tumours, such as CD8⁺ T cells, macrophages, dendritic cells and regulatory T cells. The immunomodulatory roles of microbial metabolites and pathogen-associated molecular patterns in shaping immune cell infiltration, cytokine profiles and checkpoint molecule expression are also explored. While immune checkpoint blockade (ICB) has emerged as a promising treatment of various cancers, its efficacy in GC remains unsatisfactory due to the immunosuppressive gastric TME. We therefore evaluate the intricate interplays between the gastric microbiota and immunotherapy, and suggest potential microbiota-targeting strategies (eg, microbiota modulation, probiotics supplementation and combination therapies) to enhance antitumour immune response and boost ICB efficacy. We conclude by highlighting current challenges and providing future directions for microbiota research in GC. Overall, a deeper understanding of host-microbe interactions can provide promising avenues for precision medicine and the development of microbiota-targeting interventions against GC.