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            <funder>We are grateful for support: for UBI equipment the French Government Programme Investissements d’Avenir France BioImaging [FBI, N° ANR-10-INSB-04-01]. This study was performed with the financial support from the French government (Agence Nationale de la Recherche) Investissement d’Avenir programme, Laboratoire d’Excellence “Integrative Biology of Emerging Infectious Diseases” [ANR-10-LABX-62-IBEID]; the Université Paris Est Creteil (UPEC), PHRC (Vatnimad) of the French government, SNFGE (French society of Gastroenterology Commad Support 2019), and from ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé, National Alliance for Life Sciences &amp; Health) within the framework of the Cancer Plan [HTE201601] supported by INCA, and executed within the frame of the Oncomix research program between Institut Pasteur and AP-HP.</funder>
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                <title xml:lang="en">Parvimonas micra, an oral pathobiont associated with colorectal cancer, epigenetically reprograms human colonocytes</title>
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                <title level="j">Gut microbes</title>
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                <term xml:lang="en">colonic epithelial primary cells</term>
                <term xml:lang="en">pathobionts</term>
                <term xml:lang="en">Parvimonas micra</term>
                <term xml:lang="en">DNA methylation</term>
                <term xml:lang="en">Colorectal cancer</term>
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              <p>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.</p>
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              <org type="consortium">The authors thank patients for having contributed to the present research program. We thank the bacteriology Departments of Cochin, Pitié Salpétrière, and Mondor Hospitals from APHP for providing P. micra clinical isolates (particularly Drs Asmaa Tazi, Alexandra Aubry, and Biba Nebbad) and the Collection of Institut Pasteur for providing reference strains. We acknowledge the Service de Gastroenterology (Dr M. Uzzan) and URC (F. Canoui Poitrine) of Henri Mondor, and the URC of St Antoine hospitals at APHP (Prof. T. Simon), as well as the Center for Translational Science (CRT)-Cytometry and Biomarkers Unit of Technology and Service (CB UTechS) at Institut Pasteur for their supports. We thank Claude Parsot and Shaynoor Dramsi for their dedication and inspiration in the development of this work, and Pamela Schnupf for careful reading of the manuscript.</org>
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              <addrLine>Département de Biologie cellulaire et Infection, 25-28, rue du docteur Roux, 75724 Paris Cedex 15</addrLine>
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