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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Microorganisms in Vertebrate Digestive Systems

This article is part of the Research TopicEmerging Roles of Gut Microbiota-derived Metabolites in Pathogenesis and Prevention of Inflammatory Bowel DiseaseView all articles

Elephant-derived Bacillus licheniformis Modulates Immune Cells Shedding Light on Cancer Resistance

Provisionally accepted
Xiaoyi  WangXiaoyi Wang1Min  WeiMin Wei2Yang  YiYang Yi3Jiaming  AnJiaming An3Jingjing  WangJingjing Wang3Rongjie  ZhaoRongjie Zhao3Zhan  SuZhan Su3Guozhong  JiGuozhong Ji4Xuemei  ZhangXuemei Zhang2*Xingyin  LiuXingyin Liu3,5*
  • 1The First Affiliated Hospital With Nanjing Medical University, Nanjing, China
  • 2The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, China
  • 3Southern University of Science and Technology, Shenzhen, China
  • 4The Second Affiliated Hospital of Nanjing Medical University Department of Gastroenterology, Nanjing, China
  • 5Nanjing Medical University, Nanjing, China

The final, formatted version of the article will be published soon.

Colorectal cancer (CRC) is currently a leading cause of cancer-related morbidity and mortality globally, underscoring the need for innovative therapeutic strategies. Probiotic treatment is increasingly appreciated as an innovative method for ameliorating inflammation and modulating the tumor microenvironment, especially in gastrointestinal diseases. Many bacterial species isolated from human and animal sources are proven effective in potential disease treatments. Elephants, renowned for their exceptional resistance to cancer, have traditionally been linked to their TP53 gene multiplicity. However, the potential contribution of their evolutionarily-refined gut microbiota to their remarkable cancer resistance remained largely unexplored. Here, we investigated this underexplored avenue and found that elephants possess a highly specialized gut microbiome finely tuned to metabolize complex polysaccharides. We isolated a probiotic bacterium from the elephant gut microbiota and whole genome sequencing (WGS) revealed its metabolic and functioning roles and confirmed the absence of virulence factors. We demonstrated that this elephant-derived Bacillus licheniformis can effectively alleviate gut inflammation and suppress the progression of colorectal tumors in mouse models. Transcriptomic analysis and flow cytometry revealed that B. licheniformis remodeled the immune microenvironment, specifically activating tumor-infiltrating T cell response and cell cytotoxicity. Integrative metabolomics further identified several key metabolites as potential soluble mediators correlated with tumor regression. Furthermore, experimental validations confirmed that the supernatant of B. licheniformis culture significantly enhanced cytotoxicity and upregulated p53 expression in CRC cell lines in vitro. Collectively, these findings unveil previously unrecognized therapeutic potentials inherent in elephant-derived probiotics, suggesting a mechanism of functional immune regulation for CRC prevention.

Keywords: Bacillus licheniformis, colorectal cancer, elephant, Gut Microbiota, probiotic

Received: 24 Nov 2025; Accepted: 12 Feb 2026.

Copyright: © 2026 Wang, Wei, Yi, An, Wang, Zhao, Su, Ji, Zhang and Liu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Xuemei Zhang
Xingyin Liu

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