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Dysbiosis-associated bile acids slam the brakes on immune checkpoint therapy

Chi Chun Wong1, Jun Yu1

  • 1Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.

Cancer Cell
|July 29, 2026
PubMed

Insights

Antibiotics reduce cancer immunotherapy effectiveness by altering gut bacteria. Researchers found that specific bile acids drive this resistance, with γ-glutamyl transferase (γGT) serving as a key predictive biomarker for treatment response.

Area of Science:

  • Oncology
  • Microbiome Research
  • Immunotherapy

Background:

  • Immune checkpoint inhibition (ICI) therapy is a cornerstone of cancer treatment.
  • Antibiotic use has been linked to reduced efficacy of ICI therapy.
  • The precise mechanisms underlying this negative interaction are not fully understood.

Purpose of the Study:

  • To elucidate the mechanisms by which antibiotics compromise ICI therapy efficacy.
  • To identify specific microbial or metabolic factors contributing to ICI non-response.
  • To discover predictive biomarkers for ICI therapy outcomes in patients exposed to antibiotics.

Main Methods:

  • Analysis of gut microbial composition and metabolic profiles in preclinical models and patient cohorts.
  • Investigating the role of specific microbial metabolites, particularly bile acids, in modulating anti-tumor immunity.
  • Correlation of identified biomarkers with clinical response to ICI therapy.

Main Results:

  • Antibiotic-induced gut dysbiosis promotes the accumulation of tauro-conjugated bile acids.
  • These dysbiosis-associated bile acids were identified as key drivers of resistance to immune checkpoint inhibition.
  • Elevated levels of γ-glutamyl transferase (γGT) were found to be a significant predictive biomarker for ICI non-response.

Conclusions:

  • Gut dysbiosis induced by antibiotics impairs cancer immunotherapy through specific bile acid alterations.
  • Tauro-conjugated bile acids are critical mediators of resistance to immune checkpoint inhibition.
  • γ-glutamyl transferase (γGT) emerges as a promising biomarker for predicting ICI treatment outcomes.

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