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Thus, the microbiome might be a therapeutic target for the treatment of both liver diseases and intestinal permeability. We aimed to investigate the relationship between the intestinal barrier and microbiome composition in cirrhosis and elucidate potential mechanisms for how bacteria influence permeability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analyzed the fecal permeability biomarker zonulin by ELISA and microbiome composition by 16s rDNA sequencing in a discovery (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a078) and a validation cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a090) of patients with liver cirrhosis. In the validation cohort, we analyzed the composition of the fecal metabolome by NMR spectroscopy. For mechanistic exploration, an intestinal barrier cell culture model using T84 cells was used.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In the discovery cohort (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a078, 77% Child\u2010Pugh Grade A, 21% Child\u2010Pugh Grade B, 3% Child\u2010Pugh Grade C), decreasing zonulin levels in stool over 6\u00a0months were associated with higher\n                      <jats:italic>Phascolarctobacterium<\/jats:italic>\n                      abundance in the microbiome.\n                      <jats:italic>Phascolarctobacterium<\/jats:italic>\n                      was associated with better liver function (lower bilirubin,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.04, INR\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.04, MELD Score,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.02). Lower\n                      <jats:italic>Phascolarctobacterium<\/jats:italic>\n                      levels were observed in decompensated cirrhosis and were associated with 36\u2010month mortality in two cohorts. Metabolomics analysis showed an association between\n                      <jats:italic>Phascolarctobacterium<\/jats:italic>\n                      and lower succinate levels. Succinate increased gut permeability in vitro, and\n                      <jats:italic>Phascolarctobacterium succinatutens<\/jats:italic>\n                      strains improved the intestinal permeability, potentially by alleviating the effect of succinate.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Phascolarctobacterium<\/jats:italic>\n                      may represent a candidate biomarker of adverse outcomes in cirrhosis and a promising target for further investigation as a next\u2010generation probiotic involved in gut barrier function and succinate homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial Registration<\/jats:title>\n                    <jats:p>NCT01607528, NCT03080129<\/jats:p>\n                  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