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We explored the metabolomic signature of\n                      <jats:italic>Lactobacillus lactis<\/jats:italic>\n                      and\n                      <jats:italic>Pediococcus pentosaceus<\/jats:italic>\n                      in NAFLD mice and its association in NAFLD patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We used Western diet\u2010induced NAFLD mice, and\n                      <jats:italic>L. lactis<\/jats:italic>\n                      and\n                      <jats:italic>P. pentosaceus<\/jats:italic>\n                      were administered to animals in the drinking water at a concentration of 10\n                      <jats:sup>9<\/jats:sup>\n                      CFU\/g for 8\u00a0weeks. NAFLD severity was determined based on liver\/body weight, pathology and biochemistry markers. Caecal samples were collected for the metagenomics by 16S rRNA sequencing. Metabolite profiles were obtained from caecum, liver and serum. Human stool samples (healthy control [\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a022] and NAFLD patients [\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a023]) were collected to investigate clinical reproducibility for microbiota\u2010derived metabolites signature and metabolomics biomarker.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>L. lactis<\/jats:italic>\n                      and\n                      <jats:italic>P. pentosaceus<\/jats:italic>\n                      supplementation effectively normalized weight ratio, NAFLD activity score, biochemical markers, cytokines and gut\u2010tight junction. While faecal microbiota varied according to the different treatments, key metabolic features including short chain fatty acids (SCFAs), bile acids (BAs) and tryptophan metabolites were analogously restored by both probiotic supplementations. The protective effects of indole compounds were validated with in vitro and in vivo models, including anti\u2010inflammatory effects. The metabolomic signatures were replicated in NAFLD patients, accompanied by the comparable levels of\n                      <jats:italic>Firmicutes<\/jats:italic>\n                      \/\n                      <jats:italic>Bacteroidetes<\/jats:italic>\n                      ratio, which was significantly higher (4.3) compared with control (0.6). Besides, the consequent biomarker panel with six stool metabolites (indole, BAs, and SCFAs) showed 0.922 (area under the curve) in the diagnosis of NAFLD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      NAFLD progression was robustly associated with metabolic dys\u2010regulations in the SCFAs, bile acid and indole compounds, and NAFLD can be accurately diagnosed using the metabolites.\n                      <jats:italic>L. lactis<\/jats:italic>\n                      and\n                      <jats:italic>P. pentosaceus<\/jats:italic>\n                      ameliorate NAFLD progression by modulating gut metagenomic and metabolic environment, particularly tryptophan pathway, of the gut\u2010liver axis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.634","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T09:17:14Z","timestamp":1640769434000},"source":"Crossref","is-referenced-by-count":142,"title":["<i>Lactobacillus lactis<\/i>\n                    and\n                    <i>Pediococcus pentosaceus<\/i>\n                    \u2010driven reprogramming of gut microbiome and metabolome ameliorates the progression of non\u2010alcoholic fatty liver disease"],"prefix":"10.1002","volume":"11","author":[{"given":"Jeong Seok","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Agricultural Biotechnology Center for Food and Bioconvergence Research Institute for Agricultural and Life Sciences Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gi Soo","family":"Youn","sequence":"additional","affiliation":[{"name":"Institute for Liver and Digestive Diseases Hallym University  Chuncheon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Agricultural Biotechnology Center for Food and Bioconvergence Research Institute for Agricultural and Life Sciences Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Ho","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Agricultural Biotechnology Center for Food and Bioconvergence Research Institute for Agricultural and Life Sciences Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Yong","family":"Kim","sequence":"additional","affiliation":[{"name":"ChunLab, Inc.  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