{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T16:25:17Z","timestamp":1790871917261,"version":"4.1.0"},"reference-count":67,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01 GM119174; R01 DK113196; P50 AA024333; R01 AA021890; 3U01AA026976; U01 AA 026976; R56HL141744 U01"],"award-info":[{"award-number":["R01 GM119174; R01 DK113196; P50 AA024333; R01 AA021890; 3U01AA026976; U01 AA 026976; R56HL141744 U01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K08 AA028794"],"award-info":[{"award-number":["K08 AA028794"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Exercise modulates multiple physiological systems, including skeletal muscle and the gut microbiome (GMB). Ammonia, a microbiome-derived cytotoxic metabolite, causes cellular hyperammonemic stress (HAS) in chronic diseases. We investigated the impact of voluntary wheel running (VWR) on GMB during HAS in a mouse model. Male C57BL\/6J mice were randomized to treatment with either ammonium acetate (AmAc) (2.5 mmol\/kg\/day) or vehicle for 6 weeks. Stool 16S rRNA sequencing was performed at baseline, pre-intervention, and post-intervention. GMB diversity, taxa-level abundance, and correlation analyses were performed. Overall GMB composition remained stable between baseline and pre-intervention across groups (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      &gt; 0.57;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001). Following interventions, VWR or usual activity (UA), alpha-diversity was highest in AmAc-treated, specifically AmAc-VWR, mice.\n                      <jats:italic toggle=\"yes\">Eubacterium xylanophilum<\/jats:italic>\n                      was reduced in AmAc-UA vs other groups (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05).\n                      <jats:italic toggle=\"yes\">Akkermansia<\/jats:italic>\n                      abundance declined over time in UA mice, but in AmAc-VWR mice, this depletion was reversed (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.002).\n                      <jats:italic toggle=\"yes\">Clostridium sensu stricto 1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Eubacterium ventriosum<\/jats:italic>\n                      were increased in AmAc-VWR mice (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.05). Correlation analysis revealed high stability in PBS-UA (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      = 0.667;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), moderate restructuring in AmAc-VWR (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      = 0.566;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; 0.001), and PBS-VWR (\n                      <jats:italic toggle=\"yes\">r<\/jats:italic>\n                      = 0.385;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = 0.0099). HAS-induced GMB instability, with loss of beneficial taxa, including short-chain fatty acid-producing bacteria, was partially ameliorated by VWR. Exercise-mediated GMB modulation may be a strategy to mitigate HAS-induced complications in chronic diseases.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>Voluntary exercise is recommended in chronic diseases to improve outcomes, but biological responses in disease are not well characterized. Perturbations in the metabolism of ammonia, a microbiome-generated toxin, occur in chronic diseases that can be compounded by muscle-generated ammonia during exercise. Exercise-induced molecular responses are adversely affected by hyperammonemic stress of chronic diseases, including liver cirrhosis. We investigated gut microbiome changes during voluntary wheel running, which replicates human endurance exercise in a preclinical mouse model of hyperammonemia. Adverse impacts of Hyperammonemic stress included a reduction in short-chain fatty acid producers that were reversed by voluntary wheel running. Our data lay the foundation for future studies on how endurance-type exercise promotes a favorable gut microbial composition and strategies to use exercise as a regulator of hyperammonemic stress via targeting the gut microbiome.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03194-25","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:00:18Z","timestamp":1784120418000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Voluntary wheel running modulates murine gut microbiome during hyperammonemic stress"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8883-663X","authenticated-orcid":false,"given":"Annette","family":"Bellar","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03xjacd83","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Inflammation 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