Lactococcus lactis subsp. cremoris Reprograms the Gut-Liver Axis and Protects Against Liver Injury

Abstract

Metabolic diseases are increasingly linked to dysregulation of the gut-liver axis, highlighting the therapeutic potential of probiotics. Lactococcus lactis 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.

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BibTeX RIS

BibTeX

@misc{gacasan2026lactococcus,
  title = {{Lactococcus lactis subsp. cremoris Reprograms the Gut-Liver Axis and Protects Against Liver Injury}},
  author = {C. A. G. Gacasan and J. Weinberg and G. M. Webster and C. R. Naudin and V. Tran and L. C. Askew and M. E. Barbian and D. P. Jones and R. M. Jones},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.16.752188},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.16.752188v1},
  note = {CC BY},
}

RIS

TY  - UNPB
TI  - Lactococcus lactis subsp. cremoris Reprograms the Gut-Liver Axis and Protects Against Liver Injury
AU  - C. A. G. Gacasan
AU  - J. Weinberg
AU  - G. M. Webster
AU  - C. R. Naudin
AU  - V. Tran
AU  - L. C. Askew
AU  - M. E. Barbian
AU  - D. P. Jones
AU  - R. M. Jones
PY  - 2026
DA  - 2026/09/16
PB  - bioRxiv
DO  - 10.64898/2026.09.16.752188
UR  - https://www.biorxiv.org/content/10.64898/2026.09.16.752188v1
AB  - Metabolic diseases are increasingly linked to dysregulation of the gut-liver axis, highlighting the therapeutic potential of probiotics. Lactococcus lactis 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.
ER  -

Abstract

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