Parvimonas micra, an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes

Emma Bergsten (1, 2) , Denis Mestivier (3) , Francoise Donnadieu (1) , Thierry Pedron (1, 4) , Caroline Barau (5) , Landry Tsoumtsa Meda (2) , Amel Mettouchi (2) , Emmanuel Lemichez (2) , Olivier Gorgette (6) , Mathias Chamaillard (7) , Amaury Vaysse (8) , Stevenn Volant (8) , Abiba Doukani (9) , Philippe J Sansonetti (1, 10) , Iradj Sobhani (11) , Giulia Nigro (12, 13, 1)

1 Pathogénie microbienne moléculaire
2 Toxines bactériennes - Bacterial Toxins
3 IMRB - Institut Mondor de Recherche Biomédicale
4 Bactériophage, bactérie, hôte - Bacteriophage, bacterium, host
5 PRB - Plateforme de Ressources Biologiques [Henri Mondor AP-HP, Créteil]
6 Plate-forme de bioimagerie ultrastructurale - Ultrastructural BioImaging Core Facility
7 PHYCELL - Laboratoire de Physiologie Cellulaire : Canaux ioniques, inflammation et cancer - U 1003
8 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
9 PASS - Unité Mixte de Service Production et Analyse de données en Sciences de la vie et en Santé
10 CdF (institution) - Collège de France
11 Service de gastro-entérologie [Henri Mondor AP-HP, Créteil]
12 Stroma, inflammation et réparation tissulaire - Stroma, Inflammation and Tissue Repair
13 Microenvironnement et Immunité - Microenvironment and Immunity

Recently, an intestinal dysbiotic microbiota with enrichment in oral cavity bacteria has been described in colorectal cancer (CRC) patients. Here, we characterize and investigate one of these oral pathobionts, the Gram-positive anaerobic coccus Parvimonas micra. We identified two phylotypes (A and B) exhibiting different phenotypes and adhesion capabilities. We observed a strong association of phylotype A with CRC, with its higher abundance in feces and in tumoral tissue compared with the normal homologous colonic mucosa, which was associated with a distinct methylation status of patients. By developing an in vitro hypoxic co-culture system of human primary colonic cells with anaerobic bacteria, we show that P. micra phylotype A alters the DNA methylation profile promoters of key tumor-suppressor genes, oncogenes, and genes involved in epithelial-mesenchymal transition. In colonic mucosa of CRC patients carrying P. micra phylotype A, we found similar DNA methylation alterations, together with significant enrichment of differentially expressed genes in pathways involved in inflammation, cell adhesion, and regulation of actin cytoskeleton, providing evidence of P. micra's possible role in the carcinogenic process.

Mots clés: Colorectal cancer; colonic epithelial primary cells; pathobionts; Parvimonas micra; DNA methylation

Domaines: Sciences du Vivant [q-bio]

Emma Bergsten, Denis Mestivier, Francoise Donnadieu, Thierry Pedron, Caroline Barau, et al.. Parvimonas micra, an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes. Gut microbes, 2023, 15 (2), pp.2265138. ⟨10.1080/19490976.2023.2265138⟩. ⟨pasteur-04250370⟩