Academic Journal
Parvimonas micra promotes carcinogenesis of colorectal cancer through phenyllactic acid-induced DNA damage.
| Τίτλος: | Parvimonas micra promotes carcinogenesis of colorectal cancer through phenyllactic acid-induced DNA damage. |
|---|---|
| Συγγραφείς: | Guo S; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; School of Public Health, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Cao M; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Wu J; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Ma W; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Liang D; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Xie H; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China.; Department of Anesthesia, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Xie Y; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Luo Z; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Lai P; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Liu D; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China., Zeng W; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Zheng J; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Xing M; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Yin X; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China., Xia M; School of Public Health, Sun Yat-Sen University, Guangzhou, China., He Z; Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Department of General Surgery (Colorectal Surgery), The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.; Key Laboratory of Human Microbiome and Chronic Diseases (Sun Yat-Sen University), Ministry of Education, Guangzhou, China. |
| Πηγή: | Clinical and translational medicine [Clin Transl Med] 2026 May; Vol. 16 (5), pp. e70667. |
| Τύπος έκδοσης: | Journal Article; Research Support, Non-U.S. Gov't |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Wiley Country of Publication: United States NLM ID: 101597971 Publication Model: Print Cited Medium: Internet ISSN: 2001-1326 (Electronic) Linking ISSN: 20011326 NLM ISO Abbreviation: Clin Transl Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2020- : [Hoboken, NJ] : Wiley Original Publication: Heidelberg : Springer-Verlag |
| Ιατρικοί όροι (MeSH): | Colorectal Neoplasms*/microbiology , Colorectal Neoplasms*/genetics , DNA Damage*/drug effects , Lactates*/adverse effects , Lactates*/metabolism , Carcinogenesis*, Feces/microbiology ; Animals ; Humans ; Mice ; Male ; Female ; Gastrointestinal Microbiome ; Disease Models, Animal |
| Περίληψη: | Recent studies have demonstrated the significance of gut microbiota in the colorectal cancer (CRC) pathogenesis. But their role in carcinogenesis remains to be established. Thus, we established a clinical cohort and the faecal samples from CRC and healthy control were collected. Our metagenomic analysis found that the presence of Parvimonas micra exhibited the most significant relationship with the occurrence of CRC. Increased colonisation of P. micra in CRC was validated with analysis of 1379 faecal metagenomes from eight public cohorts. Untargeted metabolomics subsequently identified an accumulation of phenyllactic acid (PLA) in faecal samples from CRC patients. Higher concentration of PLA was detected in the supernatant from our isolated P. micra. Whole-genome sequencing confirmed that a series of genes associated with PLA biosynthesis such as pdhD were observed in the P. micra genome. Importantly, both P. micra and PLA-induced carcinogenesis in ApcMin/+ and azoxymethane/dextran sulphate sodium salt mice model. The roles of P. micra and PLA in CRC development were associated with DNA damage. Engineered Escherichia coli BL21 that encoded the heterologous pdhD from P. micra could also induce DNA damage. Mechanically, PLA-induced DNA damage and CRC carcinogenesis were significantly alleviated in Ahr-/- mice. Aryl hydrocarbon receptor (AHR) inhibitor exhibited a therapeutic potential to reduce mice carcinogenesis. These findings established the role of P. micra and its metabolite, therefore providing diagnostic and therapeutic targets for treating CRC. (© 2026 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.) |
| References: | Nat Commun. 2025 Mar 07;16(1):2305. (PMID: 40055343) Bioinformatics. 2014 Aug 1;30(15):2114-20. (PMID: 24695404) Nature. 2020 Apr;580(7802):269-273. (PMID: 32106218) Nat Microbiol. 2021 Nov;6(11):1367-1382. (PMID: 34675385) Nat Commun. 2021 Sep 28;12(1):5674. (PMID: 34584098) J Exp Clin Cancer Res. 2023 Jan 10;42(1):13. (PMID: 36627634) Nat Methods. 2012 Mar 04;9(4):357-9. (PMID: 22388286) Microbiome. 2022 Feb 21;10(1):35. (PMID: 35189961) mSystems. 2019 Nov 12;4(6):. (PMID: 31719139) Nat Med. 2019 Jun;25(6):968-976. (PMID: 31171880) Cancer Discov. 2022 Jan;12(1):31-46. (PMID: 35022204) Gut. 2019 Feb;68(2):289-300. (PMID: 30377189) Nat Cell Biol. 2024 Jan;26(1):124-137. (PMID: 38168770) Nat Commun. 2015 Mar 11;6:6528. (PMID: 25758642) CA Cancer J Clin. 2025 Jan-Feb;75(1):10-45. (PMID: 39817679) Microbiome. 2023 May 8;11(1):102. (PMID: 37158970) Anaerobe. 2019 Feb;55:54-60. (PMID: 30359695) Nat Microbiol. 2024 Jun;9(6):1467-1482. (PMID: 38750176) Nat Rev Cancer. 2006 Dec;6(12):947-60. (PMID: 17128211) Nat Med. 2019 Apr;25(4):679-689. (PMID: 30936547) Cell Host Microbe. 2024 Dec 11;32(12):2080-2091.e6. (PMID: 39626677) BMC Microbiol. 2025 Nov 18;25(1):761. (PMID: 41254562) Nat Med. 2019 Apr;25(4):667-678. (PMID: 30936548) Gut. 2022 Jun;71(6):1203-1213. (PMID: 34344785) Cell Host Microbe. 2024 Nov 13;32(11):1927-1943.e9. (PMID: 39541945) J Dairy Sci. 2022 Nov;105(12):9463-9475. (PMID: 36270872) Mol Cancer. 2025 Aug 22;24(1):219. (PMID: 40847302) Gut. 2017 Jan;66(1):70-78. (PMID: 26408641) Nature. 2013 Sep 19;501(7467):426-9. (PMID: 23955152) Cancer Cell. 2021 Oct 11;39(10):1317-1341. (PMID: 34506740) Nat Rev Microbiol. 2026 Mar;24(3):197-214. (PMID: 40983729) Cancer Res. 2025 Dec 1;85(23):4600-4615. (PMID: 40953220) Cancer Res. 2021 May 15;81(10):2745-2759. (PMID: 34003774) Nat Microbiol. 2019 Dec;4(12):2319-2330. (PMID: 31501538) Nat Methods. 2018 Nov;15(11):962-968. (PMID: 30377376) Nat Med. 2025 Jul;31(7):2416-2429. (PMID: 40461820) Gut Microbes. 2023 Dec;15(2):2265138. (PMID: 37842920) Genome Biol. 2019 Nov 28;20(1):257. (PMID: 31779668) Mol Syst Biol. 2014 Nov 28;10:766. (PMID: 25432777) |
| Grant Information: | 2022YFA1304000 National Key R&D Program of China; 2024B1111150001 Guangdong S&T Program; National Key Clinical Discipline; U21A20344 National Natural Science Foundation of China; 82273346 National Natural Science Foundation of China; 2020B1111170004 Guangdong Provincial Clinical Research Center for Digestive Diseases; 2021B1212040017 Science and Technology Program of Guangdong Province, China; 2024A04J4086 Science and Technology Program of Guangdong Province, China; B2302036 Shenzhen Medical Research Special Fund Project Target disease; 2023WST03 Key Laboratory Start-Up Project (Sixth Affiliated Hospital of Sun Yat-Sen University) |
| Contributed Indexing: | Keywords: DNA damage; carcinogenesis; colorectal cancer; metabolomics; microbiota |
| Substance Nomenclature: | 0 (Lactates) 156-05-8 (3-phenyllactic acid) |
| Entry Date(s): | Date Created: 20260503 Date Completed: 20260716 Latest Revision: 20260921 |
| Update Code: | 20260921 |
| PubMed Central ID: | PMC13136068 |
| DOI: | 10.1002/ctm2.70667 |
| PMID: | 42071227 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!