Background: Altered bacterial translocation is associated with transitioning from compensated to decompensated cirrhosis. Thus, we aimed to study differences in the blood microbiome of HCV-infected patients with and without hepatic decompensation. Methods: We conducted a cross-sectional study in patients with advanced HCV-related cir-rhosis with or without human immunodeficiency virus (HIV) infection (n=88). MiSeq Illumina technology for bacterial 16S rRNA sequencing was used. Non-targeted metabolomics was performed by GC-MS and LC-MS ESI+ and ESI-. Results: Patients with decompensated cirrhosis had lower levels of richness (Chao1), and alpha diversity (Shannon and Simpson indexes) at phylum level, than patients without de-compensation. Likewise, we observed significant differences in beta diversity between groups at phylum, class and order levels, being lower in decompensated cirrhotic patients. Higher relative abundance of Proteobacteria (Fold Change (FC)=1.54, p=0.012), Alphaprote-obacteria (FC=1.57, p=0.016) and Sphingomonadales (FC=1.61, p=0.050) were significantly associated with hepatic decompensation. The phylum Proteobacteria was positively correlat-ed with ethanolamine and oleic acid (p=0.005 and p=0.004, respectively) and negatively with p-cresol (p=0.006). In addition, the order Sphingomonadales was also negatively correlated with p-cresol (p=0.001). Conclusions: Blood microbial diversity was significantly decreased in patients with decom-pensated cirrhosis, who presented an enrichment of Proteobacteria, Alphaproteobacteria, and Sphingomonadales, compared to patients with compensated cirrhosis.

The authors have declared no competing interest.

This study was supported by grants from Instituto de Salud Carlos III (ISCIII; grant numbers CP17CIII/00007, PI18CIII/00028 and PI21CIII/00033 to MAJS, PI17/00657 and PI20/00474 to JB, PI17/00903 and PI20/00507 to JGG, and PI17CIII/00003 and PI20CIII/00004 to SR) and Ministerio de Ciencia e Innovacion (PID2021-126781OB-I00 funded by MCIN/AEI/10.13039/501100011033 and by "ERDF A way of making Europe" to AFR). The study was also funded by CIBER - Consorcio Centro de Investigacion Biomedica en Red - (CB 2021; CB21/13/00044), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovacion and Union Europea - NextGenerationEU. CB and DR acknowledge funding from the Ministerio de Ciencia, Innovacion y Universidades (RTI2018-095166-B-I00). MAJS and MR are Miguel Servet researchers supported and funded by ISCIII (grant numbers: CP17CIII/00007 to MAJS and CP19CIII/00002 to MR).

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study received the approval of the Research Ethics Committee of the Instituto de Salud Carlos III (CEI42_2020, CEI41_2014) and was carried out following the Declaration of Helsinki. All participants of the study gave their written informed consent.

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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All data produced in the present study are available upon reasonable request to the authors. The raw sequences are publicly available at the European Nucleotide Archive repository (ENA; https://www.ebi.ac.uk/) under the accession number PRJEB65371

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