Microbiota utilization of intestinal amino acids modulates cancer progression and anticancer immunity

Shanshan Qiao¹, Ting-Ting Li¹, Mingeum Jeong¹, Chuanfa Liu², Sayaka Mizutani³, Sung-Min Hwang⁴, Yaxin Li⁵, Mengze Lyu⁶, Kazuhiro Nishiyama⁷, Yu-Ang Tang⁸, Huiqing Shi¹, Yuelin Angelina Tang¹, Seong-Ji Han¹, Jeremy Goc¹, Chris Parkhurst¹; JRI Live Cell Bank Consortium; Wen-Bing Jin¹, Xiaoyu Yang⁹, He S Yang⁵, Mohammad Arifuzzaman¹, Gregory F Sonnenberg¹⁰, Juan R Cubillos-Ruiz⁴, Jun Yu², Nicholas Collins¹¹, David Artis¹², Chun-Jun Guo¹³

Affiliations

¹ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
² Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, LiKaShing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
³ Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan.
⁴ Department of Obstetrics and Gynecology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁵ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁶ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁷ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Laboratory of Prophylactic Pharmacology, Osaka Metropolitan University Graduate School of Veterinary Science, Osaka 598-8531, Japan.
⁸ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁹ Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
¹⁰ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
¹¹ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address: nic4015@med.cornell.edu.
¹² Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address: dartis@med.cornell.edu.
¹³ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address: cj@guo-group.org.

PMID: 41483801
DOI: 10.1016/j.chom.2025.12.003

Microbiota utilization of intestinal amino acids modulates cancer progression and anticancer immunity

Shanshan Qiao et al. Cell Host Microbe. 2026.

. 2026 Jan 14;34(1):18-34.e14.

doi: 10.1016/j.chom.2025.12.003. Epub 2026 Jan 2.

Authors

Affiliations

¹ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
² Institute of Digestive Disease and Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, LiKaShing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
³ Juntendo University, Graduate School of Medicine, Tokyo 113-8421, Japan.
⁴ Department of Obstetrics and Gynecology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Sandra and Edward Meyer Cancer Center, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁵ Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁶ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁷ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Laboratory of Prophylactic Pharmacology, Osaka Metropolitan University Graduate School of Veterinary Science, Osaka 598-8531, Japan.
⁸ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
⁹ Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
¹⁰ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA.
¹¹ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address: nic4015@med.cornell.edu.
¹² Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address: dartis@med.cornell.edu.
¹³ Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Friedman Center for Nutrition and Inflammation, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Joan and Sanford I. Weill Department of Medicine, Gastroenterology & Hepatology Division, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA; Department of Microbiology and Immunology, Weill Cornell Medicine, Cornell University, New York, NY 10021, USA. Electronic address: cj@guo-group.org.

PMID: 41483801
DOI: 10.1016/j.chom.2025.12.003

Abstract

The human microbiota modulates cancer progression through largely unexplored mechanisms. Defining causal pathways is essential for monitoring and fine-tuning the microbiota to improve cancer treatment. Given that amino acid (aa) metabolism is often dysregulated in cancer, we assessed the role of microbiota pathways that modulate intestinal aa levels on colorectal tumor progression in mice. We found that the Bacteroides gene bo-ansB affects tumor responses to dietary asparagine (Asn) by reducing intestinal Asn levels. In mice receiving dietary Asn, bo-ansB promotes tumor progression by altering tumor-infiltrating CD8⁺ T cells. Mechanistically, bo-ansB depletes Asn in the tumor microenvironment (TME), suppressing the expression of an Asn transporter (SLC1A5) in CD8⁺ T cells and impairing their stem-like properties and effector functions. In humans, microbiota-encoded genes contributing to aa depletion are associated with colorectal cancer progression. Collectively, these findings reveal nutrient-dependent modulation of anticancer immunity by the gut microbiota and identify diet-microbiota-cancer crosstalk as a potential therapeutic target.

Keywords: Bacteroides asparaginase; CD8 T cell; amino acid transporter SLC1A5; antitumor immunity; asparagine; diet-microbiota-cancer crosstalk; gut microbiota; host-microbe interactions; microbial amino acid metabolism.

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Conflict of interest statement

Declaration of interests J.R.C.-R. holds patents on immune modulators for cancer therapy, serves as a consultant for Autoimmunity Biologic Solutions, Inc., and Emerald Bioventures, LLC, and holds stock options in Vescor Therapeutics. D.A. is on scientific advisory boards at Pfizer, Takeda, Nemagene, and the KRF.

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Microbiota utilization of intestinal amino acids modulates cancer progression and anticancer immunity

Affiliations

Microbiota utilization of intestinal amino acids modulates cancer progression and anticancer immunity

Authors

Affiliations

Abstract

Conflict of interest statement

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials