Bariatric surgery-induced gut microbiota remodeling and innate immune activation: implications for gastrointestinal cancer immunotherapy
5 affiliations
- 1Department of General Surgery, Affiliated Hospital of Zunyi Medical University
- 2Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University
- 3Department of General Surgery, Nayong County People’s Hospital
- 4Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University
- 5Guizhou Provincial Key Laboratory of Digestive System Diseases
Abstract
Bariatric and metabolic surgery (MBS)—primarily sleeve gastrectomy and Roux-en-Y gastric bypass—provides a unique human model for evaluating how profound immunometabolic rewiring alters cancer susceptibility and therapeutic responsiveness. Beyond weight loss, post-surgical anatomical reconfiguration permanently reshapes the gut microbial ecosystem, alters enterohepatic bile acid circulation, and attenuates systemic meta-inflammation. This review synthesizes emerging evidence linking post-bariatric gut microbiota remodeling to innate immune activation, with a specific focus on its translational potential in gastrointestinal (GI) cancer immunotherapy. Mechanistically, post-operative shifts in secondary bile acids, short-chain fatty acids, and microbial pattern-associated molecular patterns (PAMPs) act through key innate sensors—including FXR, TGR5, AhR, and the cGAS-STING pathway—to reprogram tumor-associated macrophages from an M2-like immunosuppressive state toward an anti-tumor phenotype. These cellular adjustments promote dendritic cell priming, stimulate type I interferon production, and enhance CXCL11-dependent cytotoxic lymphocyte recruitment, thereby remodeling “cold” gastrointestinal tumor microenvironments. By deconstructing the multi-layered crosstalk across the gut–liver and gut–tumor axes, we outline a translational framework for leveraging non-surgical surrogates—including defined microbial consortia, engineered postbiotics, and targeted pattern-recognition receptor agonists—to overcome primary resistance to immune checkpoint inhibitors in gastrointestinal malignancies.
Related
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BibTeX
@article{shen2026bariatric,
title = {{Bariatric surgery-induced gut microbiota remodeling and innate immune activation: implications for gastrointestinal cancer immunotherapy}},
author = {Bingbing Shen and Yi Luo and Xinghong Tang and Zhongbao Hu and Qiujing He and Lun Wang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.2004691},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004691/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Bariatric surgery-induced gut microbiota remodeling and innate immune activation: implications for gastrointestinal cancer immunotherapy
AU - Bingbing Shen
AU - Yi Luo
AU - Xinghong Tang
AU - Zhongbao Hu
AU - Qiujing He
AU - Lun Wang
PY - 2026
DA - 2026/10/27
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.2004691
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.2004691/full
AB - Bariatric and metabolic surgery (MBS)—primarily sleeve gastrectomy and Roux-en-Y gastric bypass—provides a unique human model for evaluating how profound immunometabolic rewiring alters cancer susceptibility and therapeutic responsiveness. Beyond weight loss, post-surgical anatomical reconfiguration permanently reshapes the gut microbial ecosystem, alters enterohepatic bile acid circulation, and attenuates systemic meta-inflammation. This review synthesizes emerging evidence linking post-bariatric gut microbiota remodeling to innate immune activation, with a specific focus on its translational potential in gastrointestinal (GI) cancer immunotherapy. Mechanistically, post-operative shifts in secondary bile acids, short-chain fatty acids, and microbial pattern-associated molecular patterns (PAMPs) act through key innate sensors—including FXR, TGR5, AhR, and the cGAS-STING pathway—to reprogram tumor-associated macrophages from an M2-like immunosuppressive state toward an anti-tumor phenotype. These cellular adjustments promote dendritic cell priming, stimulate type I interferon production, and enhance CXCL11-dependent cytotoxic lymphocyte recruitment, thereby remodeling “cold” gastrointestinal tumor microenvironments. By deconstructing the multi-layered crosstalk across the gut–liver and gut–tumor axes, we outline a translational framework for leveraging non-surgical surrogates—including defined microbial consortia, engineered postbiotics, and targeted pattern-recognition receptor agonists—to overcome primary resistance to immune checkpoint inhibitors in gastrointestinal malignancies.
SN - 1664-3224
ER -