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                <title level="j">BMC Microbiology</title>
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                  <publisher>BioMed Central</publisher>
                  <biblScope unit="volume">23</biblScope>
                  <biblScope unit="issue">1</biblScope>
                  <biblScope unit="pp">34</biblScope>
                  <date type="datePub">2023-01-30</date>
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              <idno type="doi">10.1186/s12866-023-02774-4</idno>
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                <term xml:lang="en">Liver diseases</term>
                <term xml:lang="en">Metabolic disease</term>
                <term xml:lang="en">Microbiota</term>
                <term xml:lang="en">Tissue microbiota</term>
              </keywords>
              <classCode scheme="mesh">Humans</classCode>
              <classCode scheme="mesh">DNA, Bacterial</classCode>
              <classCode scheme="mesh">RNA, Ribosomal, 16S</classCode>
              <classCode scheme="mesh">Prospective Studies</classCode>
              <classCode scheme="mesh">Fibrosis</classCode>
              <classCode scheme="mesh">Liver Cirrhosis</classCode>
              <classCode scheme="mesh">Microbiota</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.heg">Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology</classCode>
              <classCode scheme="halDomain" n="sdv.mhep.em">Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism</classCode>
              <classCode scheme="halDomain" n="sdv.mp.bac">Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology</classCode>
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              <p>Background: Gut microbiota is involved in the development of liver diseases such as fibrosis. We and others identified that selected sets of gut bacterial DNA and bacteria translocate to tissues, notably the liver, to establish a non-infectious tissue microbiota composed of microbial DNA and a low frequency live bacteria. However, the precise set of bacterial DNA, and thereby the corresponding taxa associated with the early stages of fibrosis need to be identified. Furthermore, to overcome the impact of different group size and patient origins we adapted innovative statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2), to study the early stages of the disease, were collected from Romania(n = 36), Austria(n = 10), Italy(n = 19), and Spain(n = 17). The 16S rRNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences.Results: Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50% of liver taxa associated with the early stage fibrosis were Enterobacteriaceae, Pseudomonadaceae, Xanthobacteriaceae and Burkholderiaceae. The Flavobacteriaceae and Xanthobacteriaceae discriminated between F0 and F1. Predicted metagenomics analysis identified that the preQ0 biosynthesis and the potential pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0.Conclusions: Without demonstrating causality, our results suggest first a role of bacterial translocation to the liver in the progression of fibrosis, notably at the earliest stages. Second, our statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses.</p>
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