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The pathogenesis has yet to be fully understood. We hypothesized that gut microbiome, bile acid (BA) composition and metabolites differ between cirrhotic patients with and without sarcopenia and contribute to pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Cirrhotic patients with (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a078) and without (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a038) sarcopenia and non\u2010cirrhotic controls with (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a039) and without (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a020) sarcopenia were included in this study. Faecal microbiome composition was studied by 16S rDNA sequencing, serum and faecal BA composition by ultra\u2010high\u2010performance liquid chromatography\u2013tandem mass spectrometry, and metabolite composition in serum, faeces and urine by nuclear magnetic resonance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Bacteroides fragilis<\/jats:italic>\n                      <\/jats:styled-content>\n                      ,\n                      <jats:italic>Blautia marseille<\/jats:italic>\n                      ,\n                      <jats:italic>Sutterella<\/jats:italic>\n                      spp. and\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Veillonella parvula<\/jats:italic>\n                      <\/jats:styled-content>\n                      were associated with cirrhotic patients with sarcopenia, whereas\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Bacteroides ovatus<\/jats:italic>\n                      <\/jats:styled-content>\n                      was more abundant in cirrhotic patients without sarcopenia. We observed significantly elevated secondary BAs, deoxycholic acid (DCA;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01) and lithocholic acid (LCA;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.02), and the ratios of deoxycholic acid to cholic acid (DCA:CA;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04), lithocholic acid to chenodeoxycholic acid (LCA:CDCA;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03) and 12 alpha\u2010hydroxylated to non\u201012 alpha\u2010hydroxylated BAs (12\u2010\u03b1\u2010OH:non\u201012\u2010\u03b1\u2010OH BAs;\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04) in serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia, indicating an enhanced transformation of primary to secondary BAs by the gut microbiome. CA (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.02) and the ratios of CA:CDCA (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03) and total ursodeoxycholic acid to total secondary BAs (T\u2010UDCA:total\u2010sec\u2010BAs,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03) were significantly reduced in the stool of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia. Also, valine and acetate were significantly reduced in the serum of cirrhotic patients with sarcopenia compared with cirrhotic patients without sarcopenia (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03, respectively). Multivariate logistic regression further confirmed the association of\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>B.\u00a0ovatus<\/jats:italic>\n                      <\/jats:styled-content>\n                      (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.01, odds ratio [OR]: 12.8, 95% confidence interval [CI]: 168.1; 2.2), the ratios of 12\u2010\u03b1\u2010OH:non\u201012\u2010\u03b1\u2010OH BAs (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.03, OR: 2.54, 95% CI: 0.99; 6.55) and T\u2010UDCA:total\u2010sec\u2010BAs (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04, OR: 0.25, 95% CI: 0.06; 0.98) in serum and stool CA:CDCA (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04, OR: 0.79, 95% CI: 0.62; 0.99), and serum valine (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.04, OR: 1.00, 95% CI: 1.02; 1.00) with sarcopenia in cirrhosis after correcting for the severity of liver disease and sex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study suggests a potential functional gut microbiome\u2013host interaction linking sarcopenia with the altered gut microbiomes, BA profiles and amino acids pointing towards a potential mechanistic interplay in understanding sarcopenia pathogenesis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13342","type":"journal-article","created":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:54:49Z","timestamp":1695880489000},"page":"2676-2691","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Altered gut microbiome, bile acid 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