Impact of Helicobacter pylori infection on gut and intratumoral microbiome and its association with immunotherapy response in gastrointestinal cancer.

H. pylori-positive gastric cancer patients showed higher alpha diversity in the gut microbiome associated with improved immunotherapy outcomes.

• Study recruited 218 GC patients, 134 ESCC patients, and 86 dMMR/MSI-H colorectal cancer patients with stool and tumor samples collected
• H. pylori-positive patients demonstrated higher alpha diversity and unique microbial signatures
• Higher alpha diversity was associated with increased immune-related progression-free survival (irPFS) and overall survival (irOS)
• Microbial co-occurrence network analysis revealed significantly distinct interaction patterns between H. pylori-positive and H. pylori-negative groups

The abundance of 45 gut microbiome species was significantly different between H. pylori-positive and H. pylori-negative gastric cancer patients.

• The gut microbiome of the H. pylori-positive GC group was enriched with species including Clostridium leptum, Oscillibacter sp. ER4, and Ruminococcus bromii
• These enriched species were associated with improved treatment response in GC patients
• The same species predicted poor prognosis in patients with ESCC and dMMR/MSI-H colorectal cancer
• This finding highlights that microbial associations with prognosis are cancer-type specific

Enhanced L-arginine biosynthesis was identified in the gut microbiome of H. pylori-positive gastric cancer patients.

• Functional pathway analysis of the gut microbiome revealed enhanced L-arginine biosynthesis in H. pylori-positive GC
• L-arginine biosynthesis is a metabolic pathway with known relevance to immune function and T-cell activity
• This finding suggests a potential mechanism by which H. pylori-associated microbiome changes may influence immunotherapy efficacy

Two intratumoral bacterial genera, Streptococcus and Granulicatella, were mutually exclusive with H. pylori infection in gastric cancer.

• Intratumoral microbiome analysis identified Streptococcus and Granulicatella as genera showing mutual exclusivity with H. pylori
• Enhanced L-lysine fermentation to acetate and butanoate was observed among intratumoral bacteria in H. pylori-positive patients
• These metabolic shifts suggest potential alterations in the tumor microenvironment associated with H. pylori infection status

Incorporating H. pylori infection status into microbiome-based prediction models improved accuracy for predicting immunotherapy outcomes in gastric cancer.

• A microbiome-based prediction model was constructed and evaluated for immunotherapy outcome prediction
• Addition of H. pylori infection status further improved model accuracy beyond microbiome data alone
• The authors conclude that H. pylori infection status should be considered when establishing prediction models for immunotherapy efficacy based on gut microbiome

H. pylori infection was associated with enhanced immunotherapy efficacy specifically in gastric cancer but the microbial signatures associated with this benefit predicted poor prognosis in ESCC and dMMR/MSI-H colorectal cancer.

• The cohort included 218 GC patients, 134 ESCC patients, and 86 dMMR/MSI-H colorectal cancer patients
• Species enriched in H. pylori-positive GC (e.g., Clostridium leptum, Oscillibacter sp. ER4, Ruminococcus bromii) were associated with improved GC treatment response
• The same species predicted poor prognosis in ESCC and dMMR/MSI-H CC patients
• This cancer-type-specific relationship suggests that H. pylori-associated microbial changes do not universally benefit immunotherapy across gastrointestinal cancers