ArticleEBioMedicine2024
Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid.
Article in EBioMedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 110 citations in OpenAlex.
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- Lactobacillaceae in Acute and Chronic Liver Diseases: From Microbiota Modulation to Therapeutic Potential.Probiotics and antimicrobial proteins · 2026Review
- Anti-Cancer Effects of Quercetin: What Role Does the Gut Microbiota Play?Molecules (Basel, Switzerland) · 2026Review
- How the gut microbiome affects the immunotherapy response in hepatocellular carcinoma.Cancer biology & medicine · 2026Review
- Metabolic dysfunction-associated steatotic liver disease and steatohepatitis-associated hepatocarcinoma preclinical models.Nature reviews. Gastroenterology & hepatology · 2026Review
- Global Advances in Hepatocellular Carcinoma Research and Therapy in 2025.Cancer innovation · 2026Review
- From One-Size-Fits-All to Precision Medicine: The Promise of Personalized Probiotics.Probiotics and antimicrobial proteins · 2026Review
- Bifidobacterium Breve Yang08 Alleviates Atopic Dermatitis By Enriching Akkermansia Muciniphila and Inhibiting Neutrophil Extracellular Traps Formation In Mice.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sleeve gastrectomy protects lean mice from future obesity.bioRxiv : the preprint server for biology · 2026Article
- Si-Wu-Tang Targets Microbiota Homeostasis and Intestinal Mucosal Barriers to Provide Protection Against MASLD by FavoringPharmaceuticals (Basel, Switzerland) · 2026Article
35 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGut probiotic depletion is associated with non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). Here, we investigated the prophylactic potential of Lactobacillus acidophilus against NAFLD-HCC.
methodsNAFLD-HCC conventional and germ-free mice were established by diethylnitrosamine (DEN) injection with feeding of high-fat high-cholesterol (HFHC) or choline-deficient high-fat (CDHF) diet. Orthotopic NAFLD-HCC allografts were established by intrahepatic injection of murine HCC cells with HFHC feeding. Metabolomic profiling was performed using liquid chromatography-mass spectrometry. Biological functions of L. acidophilus conditional medium (L.a CM) and metabolites were determined in NAFLD-HCC human cells and mouse organoids.
findingsL. acidophilus supplementation suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice. This was confirmed in orthotopic allografts and germ-free tumourigenesis mice. L.a CM inhibited the growth of NAFLD-HCC human cells and mouse organoids. The protective function of L. acidophilus was attributed to its non-protein small molecules. By metabolomic profiling, valeric acid was the top enriched metabolite in L.a CM and its upregulation was verified in liver and portal vein of L. acidophilus-treated mice. The protective function of valeric acid was demonstrated in NAFLD-HCC human cells and mouse organoids. Valeric acid significantly suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice, accompanied by improved intestinal barrier integrity. This was confirmed in another NAFLD-HCC mouse model induced by CDHF diet and DEN. Mechanistically, valeric acid bound to hepatocytic surface receptor GPR41/43 to inhibit Rho-GTPase pathway, thereby ablating NAFLD-HCC.
interpretationL. acidophilus exhibits anti-tumourigenic effect in mice by secreting valeric acid. Probiotic supplementation is a potential prophylactic of NAFLD-HCC.
fundingShown in Acknowledgments.
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