2. Academic Validation
  3. Bifidobacterium animalis suppresses non-small cell lung cancer progression and modulates tumor immunity through indole-3-acetic acid

Bifidobacterium animalis suppresses non-small cell lung cancer progression and modulates tumor immunity through indole-3-acetic acid

  • Cell Rep. 2025 Aug 26;44(8):116132. doi: 10.1016/j.celrep.2025.116132.
Qian Song 1,  Xinpei Li 1,  Qing Li 2,  Shijie Shang 3,  Shuling Ma 1,  Zijun Zhai 4,  Fengxin Sun 5,  You Mo 6,  Ling Wei 1,  Meng Wu 1,  Yuequn Ma 1,  Jinming Yu 7,  Dawei Chen 8
Affiliations

Affiliations

  • 1 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China.
  • 2 Dermatology Hospital, Southern Medical University, Guangzhou, China.
  • 3 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 4 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; Cheeloo College of Medicine, Shandong University Cancer Center, Jinan, Shandong, China.
  • 5 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; School of Clinical Medicine, Shandong Second Medical University, Weifang, China.
  • 6 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China; The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
  • 7 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. Electronic address: sdyujinming@163.com.
  • 8 Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, China. Electronic address: dave0505@yeah.net.
PMID: 40802513 DOI: 10.1016/j.celrep.2025.116132
Abstract

Emerging evidence implicates the significant influence of gut microbiome and its metabolic byproducts in the non-small cell lung Cancer (NSCLC). Here, we identify distinct disparity in the gut microbiota composition between patients with NSCLC and healthy controls, with Bifidobacterium animalis being markedly decreased in NSCLC. B. animalis suppresses tumor progression in two NSCLC mouse models and NSCLC cell lines. Integrative metabolomic analysis identifies indole-3 acetic acid (IAA) as the pivotal metabolite of B. animalis, with significant anti-NSCLC properties. Mechanistically, B. animalis and its derived IAA activate Aryl Hydrocarbon Receptor (AHR) in lung to suppress METTL3 and the m6A methylation of STAT3. Moreover, B. animalis and IAA diminish polarization of M2 macrophage and enhance CD8+ T cell functions by suppressing interleukin-6 (IL-6). B. animalis and its derived IAA protect against NSCLC by modulating AHR/METTL3/STAT3 and bolstering antitumor immunity through gut-lung axis. B. animalis and IAA supplementation represent a promising prophylactic for NSCLC prevention.

Keywords

AHR; Bifidobacterium animalis; CP: Cancer; CP: Microbiology; antitumor immunity; gut-lung axis; indole-3 acetic acid; non-small cell lung cancer; probiotics.

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