{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:18:33Z","timestamp":1792790313720,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,18]]},"group-title":"Microbiology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["F30DK139762"],"award-info":[{"award-number":["F30DK139762"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"National Institute of Diabetes and Digestive and Kidney Diseases","award":["F30DK134204"],"award-info":[{"award-number":["F30DK134204"]}],"id":[{"id":"https:\/\/ror.org\/00adh9b73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","award":["K12HD072245"],"award-info":[{"award-number":["K12HD072245"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,18]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Metabolic diseases are increasingly linked to dysregulation of the gut-liver axis, highlighting the therapeutic potential of probiotics.\n                  <jats:italic>Lactococcus lactis<\/jats:italic>\n                  subsp. cremoris (LLC) protects against experimental hepatic steatosis, but the mechanisms underlying its benefits remain poorly understood. Here, we integrated untargeted metabolomics, gnotobiotic mouse models, targeted bile acid profiling, and liver injury paradigms to systematically define LLC-mediated metabolic reprogramming. LLC extensively remodeled serum and hepatic metabolomes in Western diet-fed mice, enriching pathways associated with lipid metabolism, xenobiotic biotransformation, and redox homeostasis. LLC attenuated ethanol-induced steatosis and acetaminophen-induced liver injury, accompanied by activation of Nrf2-dependent antioxidant programs and FXR signaling. LLC monocolonization was sufficient to reprogram the hepatic metabolome, revealing direct host metabolic effects. Reduced intestinal bile acid conjugation emerged as a prominent LLC-associated phenotype. Together, these findings identify LLC as a probiotic that reprograms the gut-liver metabolic axis to enhance metabolic resilience and hepatoprotection.\n                <\/jats:p>","DOI":"10.64898\/2026.09.16.752188","type":"posted-content","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T05:30:17Z","timestamp":1789795817000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Lactococcus lactis<\/i>\n                  subsp. cremoris Reprograms the Gut-Liver Axis and Protects Against Liver Injury"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2527-9207","authenticated-orcid":false,"given":"C. Anthony","family":"Gacasan","sequence":"first","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaclyn","family":"Weinberg","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle M.","family":"Webster","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crystal R.","family":"Naudin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ViLinh","family":"Tran","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren C.","family":"Askew","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria E.","family":"Barbian","sequence":"additional","affiliation":[{"name":"Division of Neonatology, Department of Pediatrics, Emory University School of Medicine, Atlanta GA, 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean P.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0415-9487","authenticated-orcid":false,"given":"Rheinallt M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092312500628000_2026.09.16.752188v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0031-8"},{"key":"2026092312500628000_2026.09.16.752188v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.10.003"},{"key":"2026092312500628000_2026.09.16.752188v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.07.007"},{"key":"2026092312500628000_2026.09.16.752188v1.4","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0812874106"},{"key":"2026092312500628000_2026.09.16.752188v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.896348"},{"key":"2026092312500628000_2026.09.16.752188v1.6","doi-asserted-by":"crossref","unstructured":"Salvador AC , Huda MN , Arends D , Elsaadi AM , Gacasan AC , Brockmann GA , Valdar W , Bennett BJ , Threadgill DW . Analysis of strain, sex, and diet-dependent modulation of gut microbiota reveals candidate keystone organisms driving microbial diversity in response to American and ketogenic diets. 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