Background: Gut microbiota alteration is implicated in the pathogenesis of alcoholic liver disease (ALD) and HCC. No study has characterized the dysbiosis associated with ALD by microbial culturomics, an approach that certifies viability and allows the characterization of pathobiont strain candidates. Methods: A case-control study was conducted on patients with ALD without HCC (ALD-NoHCC) (n=16), ALD with HCC (ALD-HCC) (n=19), and controls (n=24). 16S rRNA amplicon sequencing and microbial culturomics were used as complementary methods for gut microbiome profiling. Results: By microbial culturomics, Thomasclavelia ramosa was the most enriched and detected in all ALD samples (100%), while it was cultivated in only a small proportion of controls (20%, p < 0.001). By 16S rRNA amplicon sequencing and 3-groups linear discriminant analysis, T. ramosa was increased explicitly in the ALD-HCC group (LDA-score > 5, p < 0.05). Conclusions: T. ramosa, identified by culturomics and 16 rRNA sequencing, is associated with ALD and ALD-HCC. Alongside the recently reported in vitro genotoxicity of this species in colorectal cancer, this species has been identified as a candidate oncobiont in ALD-HCC.

The authors have declared no competing interest.

This study was funded by the Agence Nationale de la Recherche under two programs: ANR-15-CE36-0004-01 and ANR "Investissements d'avenir", Mediterranee Infection 10-IAHU-03. The Region Provence-Alpes-Cote d'Azur also supported this study, which received financial support from the Fondation Mediterranee Infection.

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Ethics committee of the Institut Hospitalo Universitaire Mediterranee Infection, Marseille, France (2020/004), approved by the Protection of Persons Committee (21.04391.000046/21075) gave ethical approval for this work

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