{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T09:10:34Z","timestamp":1789031434170,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Acute-on-chronic liver failure (ACLF) is a life-threatening condition arising from the abrupt worsening of pre-existing chronic liver disease, typically accompanied by multi-organ failure and markedly elevated short-term mortality. Gut microbiota dysbiosis is frequently observed in patients with ACLF, yet the mechanisms by which microbial alterations contribute to disease progression remain unclear. Here, we investigated whether gut microbiota dysbiosis could exacerbate liver injury in ACLF and explored the underlying mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The correlation between serum lactic acid levels and liver injury in patients with ACLF was analyzed. ACLF model in SD rats was established to investigate the effects of lactate transporter inhibitor on liver injury. 16S rRNA sequencing was performed to characterize alterations in the gut microbiota of ACLF rats, and correlations between serum lactate levels, fecal lactate levels and liver injury-related indicators were evaluated. A pseudo-germ-free ACLF rat model was established to determine whether gut microbiota dysbiosis could aggravate liver injury in ACLF rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum L-lactate and D-lactate levels were significantly positively correlated with ALT levels in patients with ACLF. Moreover, inhibiting lactic acid transport exacerbated liver injury in ACLF rats. The abundance of lactate-producing bacteria, particularly\n                      <jats:italic>Lactobacillus<\/jats:italic>\n                      and\n                      <jats:italic>Ligilactobacillus<\/jats:italic>\n                      , was significantly increased in the gut of ACLF rats, accompanied by elevated lactate levels in serum, liver tissues and feces. Correlation analysis revealed strong positive associations between serum lactic acid levels, fecal lactate levels and biochemical markers of liver injury, and between D-lactate levels and the abundance of lactate-producing taxa. Moreover, transplantation of fecal microbiota from conventional ACLF rats into pseudo-germ-free ACLF rats reduced microbial diversity, enriched lactate-producing genera, increased lactic acid levels in serum, liver tissues and feces, and exacerbated liver injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggested that gut microbiota dysbiosis may contribute to ACLF progression, potentially through expansion of lactate-producing bacteria and subsequent D-lactic acid accumulation. Our results provided a conceptual basis for targeting microbial lactic acid metabolism as a therapeutic strategy for ACLF.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1851153","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:49:51Z","timestamp":1789030191000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Gut microbiota dysbiosis aggravates liver injury in acute-on-chronic liver failure through D-lactate accumulation"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhiwu","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of General Surgery, Shenzhen Bao'an District Songgang People's Hospital","place":["Shenzhen, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lining","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of General Surgery, The Second Medical Center & National Clinical Research Center for Geriatric Diseases, Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingqing","family":"Yang","sequence":"additional","affiliation":[{"name":"Medical Experimental Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhongnan Hospital of Wuhan University","place":["Wuhan, China"]},{"name":"Institute of Hepatobiliary Diseases of Wuhan University","place":["Wuhan, China"]},{"name":"Transplant Center of Wuhan University","place":["Wuhan, China"]},{"name":"National Quality Control Center for Donated Organ Procurement","place":["Wuhan, China"]},{"name":"Hubei Key Laboratory of Medical Technology on Transplantation","place":["Wuhan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2882","DOI":"10.3390\/ijms26072882","article-title":"The microbiome and metabolic dysfunction-associated steatotic liver disease","volume":"26","author":"Beyoglu","year":"2025","journal-title":"Int. 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