{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:32:58Z","timestamp":1790371978910,"version":"4.1.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"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><jats:title>Introduction<\/jats:title><jats:p>Non-alcoholic fatty liver disease (MASLD) is a common liver condition with a global prevalence of approximately 25%, often associated with overweight, obesity, and abnormalities in glucose and lipid metabolism. Its histological hallmark is hepatic steatosis. Non-alcoholic steatohepatitis (MASH), an advanced form of MASLD, can lead to cirrhosis and liver cancer. Dysbiosis of the gut microbiota plays a significant role in chronic liver diseases, making probiotic treatment a focal point in MASLD research. Studies have shown that <jats:italic>Lactobacillus rhamnosus<\/jats:italic> GG (LGG) can improve gut microbiota, reduce hepatic fat accumulation, and lower blood lipid levels in MASLD model mice. However, the role of LGG in the progression from MASLD to MASH remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we constructed MASLD and MASH models using a high-fructose, high-fat diet combined with carbon tetrachloride (CCl4) induction to explore the effects of LGG on disease progression. Our findings revealed that in the MASLD model, LGG improved lipid metabolism and inflammatory responses by modulating the gut microbiota (e.g., increasing the abundance of Bacteroidetes) and promoting the production of short-chain fatty acids (SCFAs). Additionally, LGG reduced the expression of genes related to lipogenesis, further alleviating MASLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the MASH model, LGG primarily exerted its effects by inhibiting the TGF-\u03b2\/SMAD signaling pathway and reducing the expression of pro-inflammatory factors (e.g., IL-1\u03b2, IL-6, TNF-\u03b1), thereby mitigating liver fibrosis and inflammation. Furthermore, LGG restored intestinal barrier function, reduced intestinal permeability, and prevented harmful substances like endotoxins from entering the liver, further alleviating hepatic inflammation and fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Although LGG shows promise in the treatment of MASLD and MASH, its mechanisms of action and long-term effects require further investigation. Future research should focus on optimizing the types, dosages, and treatment regimens of probiotics, as well as monitoring their long-term impact on gut microbiota balance, to ensure their safety and efficacy in clinical applications.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1586678","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T05:33:28Z","timestamp":1753335208000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Lactobacillus rhamnosus GG attenuates MASLD\/MASH progression by modulating gut microbiota and metabolic pathways"],"prefix":"10.3389","volume":"16","author":[{"given":"Shi-Long","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Wen","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zi-Yi-Ru","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Qing","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"BSR20231532","DOI":"10.1042\/BSR20231532","article-title":"A short-term rodent model for non-alcoholic steatohepatitis induced by a high-fat diet and carbon tetrachloride","volume":"44","author":"Araujo","year":"2024","journal-title":"Biosci. Rep."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"672","DOI":"10.3390\/nu15030672","article-title":"Lactobacillus rhamnosus GG promotes recovery of the Colon barrier in septic mice through accelerating ISCs regeneration","volume":"15","author":"Chen","year":"2023","journal-title":"Nutrients"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2129","DOI":"10.1016\/j.apsb.2021.12.011","article-title":"Bile acid coordinates microbiota homeostasis and systemic immunometabolism in cardiometabolic diseases","volume":"12","author":"Guan","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/s41575-023-00807-x","article-title":"Hepatic inflammatory responses in liver fibrosis","volume":"20","author":"Hammerich","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/19490976.2021.1880240","article-title":"Akkermansia muciniphila and environmental enrichment reverse cognitive impairment associated with high-fat high-cholesterol consumption in rats","volume":"13","author":"Higarza","year":"2021","journal-title":"Gut Microbes"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"e2300141","DOI":"10.1002\/mnfr.202300141","article-title":"A newly Synbiotic combination alleviates obesity by modulating the gut microbiota\u2013fat Axis and inhibiting the hepatic TLR4\/NF-\u03baB signaling pathway","volume":"67","author":"Kang","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"530","DOI":"10.1016\/j.bbrc.2016.03.107","article-title":"Protective effects of Lactobacillus rhamnosus GG against dyslipidemia in high-fat diet-induced obese mice","volume":"473","author":"Kim","year":"2016","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"111429","DOI":"10.1016\/j.intimp.2023.111429","article-title":"Magnesium isoglycyrrhizinate attenuates nonalcoholic fatty liver disease by strengthening intestinal mucosal barrier","volume":"128","author":"Lai","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"120197","DOI":"10.1016\/j.carbpol.2022.120197","article-title":"\u0391-D-1,3-glucan from Radix Puerariae thomsonii improves NAFLD by regulating the intestinal flora and metabolites","volume":"299","author":"Li","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"lxae125","DOI":"10.1093\/jambio\/lxae125","article-title":"Coprococcus protects against high-fat diet-induced nonalcoholic fatty liver disease in mice","volume":"135","author":"Lu","year":"2024","journal-title":"J. Appl. Microbiol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1038\/s41419-023-05853-6","article-title":"Butyrate limits inflammatory macrophage niche in NASH","volume":"14","author":"Sarkar","year":"2023","journal-title":"Cell Death Dis."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1352","DOI":"10.1016\/j.jhep.2023.07.005","article-title":"Bifidobacterium pseudolongum-generated acetate suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma","volume":"79","author":"Song","year":"2023","journal-title":"J. Hepatol."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"8644","DOI":"10.1039\/D4FO01059K","article-title":"Improving insulin resistance by sulforaphane via activating the Bacteroides and Lactobacillus SCFAs-GPR-GLP1 signal axis","volume":"15","author":"Tian","year":"2024","journal-title":"Food Funct."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/j.jhep.2018.03.011","article-title":"A simple diet- and chemical-induced murine NASH model with rapid progression of steatohepatitis, fibrosis and liver cancer","volume":"69","author":"Tsuchida","year":"2018","journal-title":"J. Hepatol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1534","DOI":"10.1038\/s41564-023-01418-7","article-title":"Parabacteroides distasonis uses dietary inulin to suppress NASH via its metabolite pentadecanoic acid","volume":"8","author":"Wei","year":"2023","journal-title":"Nat. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"117841","DOI":"10.1016\/j.jep.2024.117841","article-title":"Chaihu Guizhi Ganjiang decoction attenuates nonalcoholic steatohepatitis by enhancing intestinal barrier integrity and ameliorating PPAR\u03b1 mediated lipotoxicity","volume":"326","author":"Wu","year":"2024","journal-title":"J. Ethnopharmacol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1186\/s12967-024-04996-0","article-title":"Exploring the interplay of gut microbiota, inflammation, and LDL-cholesterol: a multiomics Mendelian randomization analysis of their causal relationship in acute pancreatitis and non-alcoholic fatty liver disease","volume":"22","author":"Yan","year":"2024","journal-title":"J. Transl. Med."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1294826","DOI":"10.3389\/fcimb.2023.1294826","article-title":"Association between gut microbiota and NAFLD\/NASH: a bidirectional two-sample Mendelian randomization study","volume":"13","author":"Zhai","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"8536","DOI":"10.1021\/acs.jafc.3c08910","article-title":"Probiotic mixture ameliorates a diet-induced MASLD\/MASH murine model through the regulation of hepatic lipid metabolism and the gut microbiome","volume":"72","author":"Zhang","year":"2024","journal-title":"J. Agric. Food Chem."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"15125","DOI":"10.1021\/acsnano.3c04449","article-title":"Gut microbiota participates in polystyrene microplastics-induced hepatic injuries by modulating the gut-liver Axis","volume":"17","author":"Zhang","year":"2023","journal-title":"ACS Nano"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3748\/wjg.v23.i1.60","article-title":"Sodium butyrate attenuates high-fat diet-induced steatohepatitis in mice by improving gut microbiota and gastrointestinal barrier","volume":"23","author":"Zhou","year":"2017","journal-title":"World J. Gastroenterol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"329","DOI":"10.3390\/antiox13030329","article-title":"Roles of traditional and next-generation probiotics on non-alcoholic fatty liver disease (NAFLD) and non-alcoholic Steatohepatitis (NASH): a systematic review and network Meta-analysis","volume":"13","author":"Zhu","year":"2024","journal-title":"Antioxidants (Basel)"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1586678\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T05:33:30Z","timestamp":1753335210000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1586678\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":22,"alternative-id":["10.3389\/fmicb.2025.1586678"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1586678","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]},"article-number":"1586678"}}