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

Sep 30, 2026

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Pentadecanoic acid (PEA), an odd-chain fatty acid shaped by gut microbiome metabolism, is increasingly linked to systemic health benefits, yet its role in bladder cancer (BC) development and invasion is unclear. Large-scale cohort analyses assessed associations between dietary PEA and BC, complemented by EJ/T24 cell assays and a BBN-induced mouse model. Serum proteomics, gut microbiome profiling, and targeted fecal lipidomics clarified mechanisms, showing PEA-mediated suppression of BC progression via lipid-metabolism pathway modulation and gut-bladder axis remodeling.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Abstract

Background

Methods

Results

Conclusions

Background

Pentadecanoic acid and dietary relevance

Bladder cancer and dietary factors

Chen et al. BMC Medicine (2026) 24:10 [https://doi.org/10.1186/s12916-025-04554-5](https://doi.org/10.1186/s12916-025-04554-5) BMC Medicine RESEARCH Open Access Integration of gut microbiome and lipid metabolism reveals the anti-cancer effects of pentadecanoic acid on bladder cancer Ya-Ting Chen1,2†, Jing Sui1,3†, Yu Yang1,4†, Hao Zhang5†, Anke Wesselius6, Yingzhou Shen7, Qi-Rong Qin8,9,10, Gui-Ju Sun 1,4, Shao-Kang Wang1,4, Xiang-Dong Wang11,12, Shujin Wang13, Wen-Chao Li 14, Kar Keung Cheng15, Nicholas D. James 16,17, Richard T. Bryan 16, Maurice P. Zeegers6, Lianmin Chen18,19*, Hui Xia1,4* and Evan Yi-Wen Yu1,2,6* 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 andT24 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 andT24 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 gutbladder 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, Pentadecanoic acid, Gut microbiome, Lipid metabolism, Gut-bladder axis †Ya-Ting Chen, Jing Sui, Yu Yang and Hao Zhang contributed equally to this work. *Correspondence: Lianmin Chen [lianminchen@njmu.edu.cn](lianminchen@njmu.edu.cn)[ ](lianminchen@njmu.edu.cn)Hui Xia [huixia@seu.edu.cn](huixia@seu.edu.cn) Evan Yi-Wen Yu [evan.yu@maastrichtuniversity.nl](evan.yu@maastrichtuniversity.nl) Full list of author information is available at the end of the article © The Author(s) 2025. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.org/licenses/by-nc-n

FAQs

What is the main question this study addresses about pentadecanoic acid (PEA)?

Whether dietary PEA is associated with bladder cancer occurrence and invasion, and how it may exert anti-cancer effects through the gut microbiome and lipid metabolism pathways.

How did the researchers test the impact of PEA on bladder cancer?

They combined large-scale cohort analyses with in vitro EJ and T24 bladder cancer cell assays and an in vivo BBN-induced mouse model.

What mechanisms were identified for PEA’s anti-cancer effects?

PEA was linked to changes in lipid-related proteins in serum proteomics, reshaping of gut microbiome composition, and shifts in fecal lipids such as phosphatidylethanolamines, implicating regulation of lipid metabolism via the gut-bladder axis.

Sep 30, 2026

Uploaded by Aran