Osswald, Annika and Wortmann, Esther and Wylensek, David and Kuhls, Stephanie and Coleman, Olivia and Peuker, Kenneth and Strigli, Anne and Ducarmon, Quinten R. and Larralde, Martin and Liang, Wei and Treichel, Nicole S. and Schumacher, Fabian and Volet, Colin and Matysik, Silke and Kleigrewe, Karin and Gigl, Michael and Rohn, Sascha and Guo, Chun-Jun and Kleuser, Burkhard and Liebisch, Gerhard and Schnieke, Angelika and Ridlon, Jason M. and Bernier-Latmani, Rizlan and Zeller, Georg and Zeissig, Sebastian and Haller, Dirk and Flisikowski, Krzysztof and Clavel, Thomas and Ocvirk, Soeren (2026) Secondary bile acid production by gut bacteria promotes Western diet-associated colorectal cancer. GUT, 75. pp. 1505-1519. ISSN 0017-5749, 1468-3288
Full text not available from this repository.Abstract
Background Western diet and associated production of secondary bile acids (BAs) have been linked to the development of sporadic colorectal cancer (CRC). Despite observational studies showing that secondary BAs produced by 7 alpha-dehydroxylating (7 alpha DH+) gut bacteria are increased in CRC, a causal proof of their tumour-promoting effects is lacking.Objective Investigate the causal role of BAs produced by 7 alpha DH+ gut bacteria in CRC.Design We performed feeding studies in a porcine model of CRC combined with multi-omics analyses and gnotobiotic mouse models colonised with 7 alpha DH+ bacteria or a genetically modified strain to demonstrate causality.Results Western diet exacerbated the CRC phenotype in APC1311/+ pigs. This was accompanied by increased levels of the secondary BA deoxycholic acid (DCA) and higher colonic epithelial cell proliferation. The latter was counteracted by the BA-scavenging drug colestyramine. Metagenomic analysis across multiple human cohorts revealed higher occurrence of bai (BA inducible) operons from Clostridium scindens and close relatives in faeces of patients with CRC. Addition of these specific 7 alpha DH+ bacteria (C. scindens/Extibacter muris) to defined communities of gut bacteria led to DCA production and increased colon tumour burden in mouse models of chemically or genetically induced CRC. A mutant strain of Faecalicatena contorta lacking 7 alpha DH caused fewer colonic tumours in azoxymethane/dextran sodium sulfate treated mice and triggered less epithelial cell proliferation in human colon organoids compared with wild-type F. contorta.Conclusion This work provides functional evidence for the causal role of secondary BAs produced by gut bacteria through 7 alpha DH in CRC under adverse dietary conditions, opening avenues for future preventive strategies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SEQUENCES; GROWTH; BILE ACID METABOLISM; BILE ACID; COLORECTAL CANCER; DIETARY - COLON CANCER; MICROBIOME |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 01 Oct 2026 07:36 |
| Last Modified: | 01 Oct 2026 07:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67930 |
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