Association of gut microbiota composition and microbe-host interactions with response to chemoimmunotherapy in...

Immune checkpoint inhibitors combined with chemotherapy have improved outcomes for advanced gastric cancer, yet only a subset of patients derive benefit, and the contribution of the gut microbiome remains incompletely defined. To identify microbial signatures associated with chemoimmunotherapy response, we performed 16S rRNA gene sequencing on 90 fecal samples collected from 30 patients at baseline, one month after treatment initiation, and at the end of therapy. Patients were stratified by RECIST1.1 criteria into partial response (PR), stable disease (SD), and progressive disease (PD). While overall microbial composition and alpha diversity remained stable over time, immunotherapy enriched Lachnospiraceae and Bacteroidaceae. Notably, baseline microbiota differed significantly among response groups: Senegalimassilia and Lactobacillus were overrepresented in PR patients, whereas Parvimonas, Intestinibacter, and Catenibacterium characterized the SD and PD groups. By integrating public databases, we constructed microbe-metabolite-target and microbe-host interaction networks, indicating that response-associated genera may modulate host genes such as IFNG, IL12B, CXCL6, and DUOX2, thereby influencing CD8⁺ T cell infiltration. These findings identify gut microbial signatures as predictive biomarkers and provide mechanistic insight into microbiome-mediated chemoimmunotherapy efficacy in gastric cancer.