2. Academic Validation
  3. Integration of gut microbiome and lipid metabolism reveals the anti-cancer effects of pentadecanoic acid on bladder cancer

Integration of gut microbiome and lipid metabolism reveals the anti-cancer effects of pentadecanoic acid on bladder cancer

  • BMC Med. 2025 Dec 3;24(1):10. doi: 10.1186/s12916-025-04554-5.
Ya-Ting Chen # 1 2,  Jing Sui # 1 3,  Yu Yang # 1 4,  Hao Zhang # 5,  Anke Wesselius 6,  Yingzhou Shen 7,  Qi-Rong Qin 8 9 10,  Gui-Ju Sun 1 4,  Shao-Kang Wang 1 4,  Xiang-Dong Wang 11 12,  Shujin Wang 13,  Wen-Chao Li 14,  Kar Keung Cheng 15,  Nicholas D James 16 17,  Richard T Bryan 16,  Maurice P Zeegers 6,  Lianmin Chen 18 19,  Hui Xia 20 21,  Evan Yi-Wen Yu 22 23 24
Affiliations

Affiliations

  • 1 Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China.
  • 2 Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing, 210009, China.
  • 3 Research Institute for Environment and Health, Nanjing University of Information Science and Technology, Nanjing, 210044, China.
  • 4 Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, 210009, China.
  • 5 Department of Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China.
  • 6 Department of Epidemiology, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6229ER, The Netherlands.
  • 7 Department of Gastroenterology, Ma'anshan People's Hospital, Ma'anshan, 243000, China.
  • 8 Ma'anshan Center for Disease Control and Prevention, Ma'anshan, 243000, China.
  • 9 The Affiliated Ma'anshan Center for Disease Control and Prevention of Anhui Medical University, Ma'anshan, 243000, China.
  • 10 Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, 230032, China.
  • 11 Nutrition and Cancer Biology Laboratory, Jean Mayer USDA Human Nutrition Research Center On Aging at Tufts University, Boston, MA, 02111, USA.
  • 12 Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA, 02111, USA.
  • 13 Center for Obesity and Metabolic Diseases Research, School of Basic Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing Medical University, Chongqing, China.
  • 14 Department of Urology, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, China.
  • 15 Department of Applied Health Research, University of Birmingham, Birmingham, B152TT, UK.
  • 16 Bladder Cancer Research Centre, College of Medicine and Health, University of Birmingham, Birmingham, B152TT, UK.
  • 17 Institute of Cancer Research, London, SW7 3RP, UK.
  • 18 Changzhou Medical Center, The Third Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Changzhou, 213003, China. [email protected].
  • 19 Department of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing Medical University, Nanjing, 210029, China. [email protected].
  • 20 Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China. [email protected].
  • 21 Department of Nutrition and Food Hygiene, School of Public Health, Southeast University, Nanjing, 210009, China. [email protected].
  • 22 Key Laboratory of Environmental Medicine and Engineering of Ministry of Education, School of Public Health, Southeast University, Nanjing, 210009, China. [email protected].
  • 23 Department of Epidemiology & Biostatistics, School of Public Health, Southeast University, Nanjing, 210009, China. [email protected].
  • 24 Department of Epidemiology, School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, 6229ER, The Netherlands. [email protected].
  • # Contributed equally.
PMID: 41339867 DOI: 10.1186/s12916-025-04554-5
Abstract

Background: Pentadecanoic acid (PEA), an odd-chain fatty acid derived from diet by the gut microbiome, has garnered increasing attention for its systemic health-promoting properties. Its potential role in bladder Cancer (BC) occurrence and invasion, however, remains unclear.

Methods: Large-scale cohorts' analyses were performed to assess the association between dietary PEA and BC occurrence and invasion. In vitro and in vivo experiments, including EJ and T24 BC cell assays and a BBN-induced mouse model, were conducted to experimentally assess the impact of PEA on BC. Serum proteomics, gut microbiome, and targeted fecal lipidomics analyses were employed to explore the underlying mechanisms.

Results: Dietary PEA was negatively associated with BC occurrence and invasion in cohort analyses. PEA suppressed EJ and T24 BC cell migration, invasion, and proliferation, while inhibiting BC development in a BBN-induced mouse model. In vivo serum proteomics identified differentially expressed lipid-related proteins (e.g., apoE and apoB) following PEA treatment, implicating its modulation of lipid metabolism pathways. Considering the essential role of the gut-bladder axis, the gut microbiome analysis exhibited that PEA markedly altered bacteria (e.g., g_Alistipes) and fungi (e.g., o_Erysiphales, g_Teberdinia, and g_Gibberella), with concomitant lipid metabolism changes. Furthermore, targeted fecal lipidomics demonstrated the shifts in key lipids, such as phosphatidylethanolamines (PE) involved in essential lipid clusters, suggesting regulation by gut microbiome linked to BC development.

Conclusions: Collectively, our findings demonstrate that PEA mitigates BC by reshaping the gut microbiome and modulating lipid metabolism, providing new insights into its molecular and therapeutic potential.

Keywords

Bladder cancer; Gut microbiome; Gut-bladder axis; Lipid metabolism; Pentadecanoic acid.

Figures
Products