{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T00:10:10Z","timestamp":1793059810201,"version":"4.5.0"},"reference-count":52,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82302566"],"award-info":[{"award-number":["82302566"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32172872"],"award-info":[{"award-number":["32172872"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"MOST | National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32202889"],"award-info":[{"award-number":["32202889"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"crossref","award":["BX20220131"],"award-info":[{"award-number":["BX20220131"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Guangdong Basic Research Program and applied basic research project","award":["SL2022A04J00581"],"award-info":[{"award-number":["SL2022A04J00581"]}]},{"name":"GDSTC | Basic and Applied Basic Research Foundation of Guangdong Province","award":["2022A1515110966"],"award-info":[{"award-number":["2022A1515110966"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2024,10,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Leptospirosis is a re-emerging worldwide zoonotic disease. Infected patients and animals often exhibit intestinal symptoms. Mounting evidence suggests that host immune responses to bacterial infection are closely associated with intestinal homeostasis. Our previous research has shown that the gut microbiota can protect the host from acute leptospirosis, while the specific bacterial metabolic mediators participating in the pathogenesis remain to be identified. Short-chain fatty acids (SCFAs) are metabolites produced mainly by the gut microbiota that play a role in immune regulation. However, whether SCFAs are the key to protecting the host against leptospirosis and the underlying regulatory mechanisms are unknown. In this study, our results showed that the SCFA butyrate is involved in ameliorating leptospirosis. The depletion of SCFAs by antibiotic cocktail treatment reduced survival time after\n                      <jats:italic>Leptospira<\/jats:italic>\n                      infection while supplementation with butyrate but not acetate or propionate significantly amelioration of leptospirosis.\n                      <jats:italic>In vitro<\/jats:italic>\n                      experiments showed that butyrate treatment enhanced the intracellular bactericidal activity mediated by reactive oxygen species (ROS) production. Mechanistically, butyrate functions as a histone deacetylase 3 inhibitor (HDAC3i) to promote ROS production\n                      <jats:italic>via<\/jats:italic>\n                      monocarboxylate transporter (MCT). The protection of butyrate against acute leptospirosis mediated by ROS was also proven\n                      <jats:italic>in vivo<\/jats:italic>\n                      . Collectively, our data provide evidence that the butyrate-MCT-HDAC3i-ROS signaling axis is a potential therapeutic target for acute leptospirosis. Our work not only interprets the microbial metabolite signaling involved in transkingdom interactions between the host and gut microbiota but also provides a possible target for developing a prevention strategy for acute leptospirosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Leptospirosis is a worldwide zoonotic disease caused by\n                      <jats:italic>Leptospira<\/jats:italic>\n                      . An estimated 1 million people are infected with leptospirosis each year. Studies have shown that healthy gut microbiota can protect the host against leptospirosis but the mechanism is not clear. This work elucidated the mechanism of gut microbiota protecting the host against acute leptospirosis. Here, we find that butyrate, a metabolite of gut microbiota, can improve the survival rate of hamsters with leptospirosis by promoting the bactericidal activity of macrophages. Mechanistically, butyrate upregulates reactive oxygen species (ROS) levels after macrophage infection with\n                      <jats:italic>Leptospira<\/jats:italic>\n                      by inhibiting HDAC3. This work confirms the therapeutic potential of butyrate in preventing acute leptospirosis and provides evidence for the benefits of the macrophage-HDAC3i-ROS axis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01906-24","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T13:01:26Z","timestamp":1726578086000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":14,"title":["Gut microbiota-derived butyrate improved acute leptospirosis in hamster\n                    <i>via<\/i>\n                    promoting macrophage ROS mediated by HDAC3 inhibition"],"prefix":"10.1128","volume":"15","author":[{"given":"Xi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, 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