Longitudinal gut microbiome dynamics during immunotherapy identify microbial features of clinical benefit in advanced primary liver cancer.

A 16-species gut microbiome panel discovered from on-treatment stool metagenomes at ~6 months (T2) predicts immunotherapy benefit in 315 patients with advanced primary liver cancer.

• Why it matters: Temporal microbiome dynamics during immune checkpoint inhibitor therapy are poorly defined, limiting whether pretreatment biomarkers can be identified and generalized across studies.
• What they did: In a prospective longitudinal shotgun metagenomic study, 777 serial stool samples were profiled at baseline and ~3-month intervals; responders had durable clinical benefit ≥6 months. On-treatment contrast at T2 was used to discover a 16-species panel, then baseline-trained models were tested across nine public ICI cohorts (n=1204).
• The result: The baseline model using the T2-derived panel outperformed baseline-only discovery and stratified overall and progression-free survival (HRs 0.49 and 0.44) in the discovery cohort and across external datasets, including stable-disease subsets.

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