Thomasclavelia ramosa is a Specific Signature of Hepatocellular Carcinoma among Patients with Alcohol-Related Liver Disease: A Culturomics and Metagenomics Case-Control Study | Thomasclavelia ramosa est une signature spécifique du carcinome hépatocellulaire chez les patients atteints de maladie alcoolique du foie : Une étude cas-témoins de Culturomics et Metagenomics

International audience

English. Backgroundalcohol abuse has deleterious effects on human health by disrupting the functions of many organs and systems, especially the liver, leading to fatal complications such as hepatocellular carcinoma (HCC). Gut microbiota has been implicated in the pathogenesis of alcoholic liver diseases (ALD) and a variety of organ malignancies such as HCC. Current studies revealed that gut microbiota can be used as a biomarker to predict cancers. Methodsa case-control study was conducted on patients with ALD without HCC (ALD_NoHCC) (n=16) and ALD with HCC (ALD_HCC) (n=19) and controls (n=24) groups. The culturomics approach was used for the first time, in addition to 16S rRNA sequencing, to analyze the patients' fecal samples. The taxonomic composition of the gut microbiota and correlation analysis to the fecal and clinical indicators were studied. ResultsCompared to the control group, the gut microbiota of the patients in the ALD_NoHCC and ALD_HCC groups showed significant changes using 16S rRNA sequencing. In ALD_NoHCC, Mediterraneibacter gnavus was significantly increased, while Thomasclavelia ramosa and Gemmiger formicilis were significantly increased in the ALD_HCC group. Alpha diversity was significantly lower in both disease groups compared to the control. Using culturomics, a total of 292 species were isolated from ALD samples, whereas 254 species were isolated from the control samples (p= 0.0342). Thomasclavelia ramosa was confirmed to be significantly enriched in all ALD samples. Patients with ALD_NoHCC and ALD_HCC showed a significant decrease in fecal total cholesterol and triglycerides (p <0.0001). Conclusionsour study reported T. ramosa in HCC for the first time. This species can be used as potential noninvasive biomarkers for diagnosing the progression of ALD to HCC, especially since it has been documented in different types of cancers. Therefore, experimental studies are needed to investigate their carcinogenic role further in addition to disease prediction models for ALD and HCC risk prediction.