{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:22:54Z","timestamp":1787851374060,"version":"build-2784847793"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"13","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":50,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"cardiovascular medicine, University of michigan","award":["233646"],"award-info":[{"award-number":["233646"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82270496,82070649"],"award-info":[{"award-number":["82270496,82070649"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,1]]},"abstract":"<jats:p>\n                    The global prevalence of metabolic dysfunction\u2013associated steatohepatitis (MASH) is rising, driven by a complex interplay of metabolic disturbances, inflammation, and fibrosis, yet effective treatment options remain limited. This study examined the relationships among intestinal microbial dysbiosis, ammonia production, and hepatic CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell activity in MASH, then assessed the therapeutic potential of DT-109, a glycine-based tripeptide. We investigated the gut\/liver axis across human cohorts and both nonhuman primate and mouse MASH models. Multiomics approaches were used to characterize ileal microbiota, ammonia levels, and hepatic immune and metabolic pathways. Causality was verified through microbiota transplantation,\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>perfringens<\/jats:italic>\n                    <jats:italic>NirA<\/jats:italic>\n                    -knockout mutants, and functional validation in vitro and in vivo. The efficacy of DT-109 was evaluated in nonhuman primates and mice. Our results revealed a significant increase in the ammonia-producing gut bacterium\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>perfringens<\/jats:italic>\n                    , which led to elevated intestinal ammonia and disruption of the intestinal barrier in MASH. Elevated ammonia levels triggered FosB-mediated upregulation of\n                    <jats:italic>CCL5<\/jats:italic>\n                    in CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, which in turn drove T cell cytotoxicity in the liver. Notably, DT-109 effectively lowered\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>perfringens<\/jats:italic>\n                    abundance, reduced intestinal ammonia, restored intestinal barrier integrity, and alleviated CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell dysregulation in MASH. These results identify a distinct mechanism in which gut-derived ammonia drives CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell\u2013mediated MASH and demonstrate that DT-109 effectively targets this axis by inhibiting\n                    <jats:italic>C<\/jats:italic>\n                    .\n                    <jats:italic>perfringens<\/jats:italic>\n                    and reducing ammonia, ultimately ameliorating MASH.\n                  <\/jats:p>","DOI":"10.1172\/jci200522","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:00:20Z","timestamp":1778601620000},"source":"Crossref","is-referenced-by-count":2,"title":["Metabolic dysfunction\u2013associated steatohepatitis exacerbated by Clostridium perfringens\u2013derived ammonia is attenuated by tripeptide DT-109"],"prefix":"10.1172","volume":"136","author":[{"given":"Pengxiang","family":"Qu","sequence":"first","affiliation":[{"name":"Laboratory Animal Center, School of Basic Medical Science, Xi\u2019an Jiaotong University; 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