{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T19:07:27Z","timestamp":1788116847415,"version":"build-2803163510"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T00:00:00Z","timestamp":1736208000000},"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":"Objective<\/jats:title>This study investigates the protective effects of lactic acid, a metabolite of Bifidobacterium<\/jats:italic>, on non-alcoholic fatty liver disease (NAFLD) induced by a high-sugar, high-fat diet (HFD) in mice, in the context of the gut-liver axis.<\/jats:p><\/jats:sec>Methods<\/jats:title>A NAFLD mouse model was established using a HFD, and different intervention groups were set up to study the protective effects of Bifidobacterium<\/jats:italic> and its metabolite lactic acid. The groups included a control group, NAFLD group, Bifidobacterium<\/jats:italic> treatment group, Glyceraldehyde-3-P (G-3P) co-treatment group, and NOD-like receptor family pyrin domain containing 3 (NLRP3) overexpression group. The evaluation of liver function and lipid metabolism was conducted using the liver-to-body weight ratio, histological staining, and biochemical assays. Enzyme-linked immunosorbent assay (ELISA) was performed to measure inflammatory cytokines, and western blotting was used to analyze the expression of NLRP3 inflammasome and autophagy-related molecules. In vitro<\/jats:italic>, an NAFLD cell model was established using oleic acid, with cells treated with lactic acid and NLRP3 overexpression to assess lipid droplet accumulation and inflammation.<\/jats:p><\/jats:sec>Results<\/jats:title>In vivo<\/jats:italic> findings indicated that, in comparison to CBX group (Control group without antibiotic treatment), NAFLD\/CBX group (NAFLD group without antibiotic administration) and NAFLD\/ABX group (NAFLD group with antibiotic administration) exhibited increased liver-to-body weight ratio, higher lipid droplet accumulation, aggravated liver histopathological damage, and elevated levels of AST (Aspartate Aminotransferase), ALT (Alanine Aminotransferase), TC (Total Cholesterol), TG (Triglycerides), LDL-C (Low-Density Lipoprotein Cholesterol), IL-6 (Interleukin-6), TNF-\u03b1 (Tumor Necrosis Factor-alpha), IL-1\u03b2 (Interleukin-1 beta), and NLRP3-related molecules, while HDL-C (High-Density Lipoprotein Cholesterol) levels significantly decreased. Intervention with Bifidobacterium<\/jats:italic> significantly reversed these adverse changes. Further addition of G-3P led to more pronounced improvement in NAFLD symptoms, while overexpression of NLRP3 weakened the protective effects of Bifidobacterium<\/jats:italic>. In vitro<\/jats:italic> results indicated that Ole group exhibited heightened lipid droplet accumulation and expression of NLRP3 inflammasome-related molecules relative to the control group. Treatment with lactic acid effectively reversed these changes; however, the protective effect of lactic acid was significantly weakened with NLRP3 overexpression.<\/jats:p><\/jats:sec>Conclusion<\/jats:title>Lactic acid can alleviate lipid metabolism disorders in NAFLD induced by diet through the inhibition of inflammation mediated by the NLRP3 inflammasome and the regulation of the autophagy process.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1518150","type":"journal-article","created":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T07:06:04Z","timestamp":1736233564000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Exploring the alleviating effects of Bifidobacterium metabolite lactic acid on non-alcoholic steatohepatitis through the gut-liver axis"],"prefix":"10.3389","volume":"15","author":[{"given":"Hongmei","family":"Zhao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingzhi","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"9478630","DOI":"10.1155\/2018\/9478630","article-title":"Probiotic species in the modulation of gut microbiota: an overview","volume":"2018","author":"Azad","year":"2018","journal-title":"Biomed. Res. Int"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1347","DOI":"10.1042\/CS20220572","article-title":"Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways","volume":"136","author":"Badmus","year":"2022","journal-title":"Clin. Sci"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1858","DOI":"10.1053\/j.gastro.2022.01.058","article-title":"Nonalcoholic fatty liver disease and the gut-liver axis: exploring an undernutrition perspective","volume":"162","author":"Bauer","year":"2022","journal-title":"Gastroenterology"},{"key":"B4","doi-asserted-by":"publisher","first-page":"248682","DOI":"10.1136\/bcr-2021-248682","article-title":"Heart failure decompensation alerts in a patient's home using an automated, AI-driven, point-of-care device","volume":"15","author":"Chausiaux","year":"2022","journal-title":"BMJ Case Rep"},{"key":"B5","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1053\/j.gastro.2023.01.040","article-title":"PNPLA3 genotype and diabetes identify patients with nonalcoholic fatty liver disease at high risk of incident cirrhosis","volume":"164","author":"Chen","year":"2023","journal-title":"Gastroenterology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"4368","DOI":"10.3748\/wjg.v29.i28.4368","article-title":"Microbiota revolution: how gut microbes regulate our lives","volume":"29","author":"Colella","year":"2023","journal-title":"World J. Gastroenterol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1970","DOI":"10.1021\/acs.jafc.2c06894","article-title":"Bifidobacterium bifidum ameliorates DSS-induced colitis in mice by regulating AHR\/NRF2\/NLRP3 inflammasome pathways through indole-3-lactic acid production","volume":"71","author":"Cui","year":"2023","journal-title":"J. Agric. Food Chem"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.4254\/wjh.v10.i1.1","article-title":"Role of inflammatory response in liver diseases: therapeutic strategies","volume":"10","author":"Del Campo","year":"2018","journal-title":"World J. Hepatol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1007\/978-3-319-48382-5_19","article-title":"Non-alcoholic fatty liver disease","volume":"960","author":"Engin","year":"2017","journal-title":"Adv. Exp. Med. Biol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.3390\/nu14061171","article-title":"High-salt diet induces depletion of lactic acid-producing bacteria in murine gut","volume":"14","author":"Hamad","year":"2022","journal-title":"Nutrients"},{"key":"B11","doi-asserted-by":"publisher","first-page":"777147","DOI":"10.3389\/fimmu.2021.777147","article-title":"Effect of extracellular vesicles derived from Lactobacillus plantarum Q7 on gut microbiota and ulcerative colitis in mice","volume":"12","author":"Hao","year":"2021","journal-title":"Front. Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"9702","DOI":"10.7150\/thno.44297","article-title":"Fibrinogen-like protein 2 aggravates nonalcoholic steatohepatitis via interaction with TLR4, eliciting inflammation in macrophages and inducing hepatic lipid metabolism disorder","volume":"10","author":"Hu","year":"2020","journal-title":"Theranostics"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1038\/s12276-023-01047-4","article-title":"Thrap3 promotes nonalcoholic fatty liver disease by suppressing AMPK-mediated autophagy","volume":"55","author":"Jang","year":"2023","journal-title":"Exp. Mol. Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1038\/s41598-022-06542-8","article-title":"Pemafibrate suppresses NLRP3 inflammasome activation in the liver and heart in a novel mouse model of steatohepatitis-related cardiomyopathy","volume":"12","author":"Kanno","year":"2022","journal-title":"Sci. Rep"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1216674","DOI":"10.3389\/fmicb.2023.1216674","article-title":"Probiotics: mechanism of action, health benefits and their application in food industries","volume":"14","author":"Latif","year":"2023","journal-title":"Front. Microbiol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2351","DOI":"10.7150\/thno.70692","article-title":"SNX10-mediated degradation of LAMP2A by NSAIDs inhibits chaperone-mediated autophagy and induces hepatic lipid accumulation","volume":"12","author":"Lee","year":"2022","journal-title":"Theranostics"},{"key":"B17","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1016\/j.chom.2018.11.002","article-title":"Microbiota-derived lactate accelerates intestinal stem-cell-mediated epithelial development","volume":"24","author":"Lee","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B18","doi-asserted-by":"publisher","first-page":"2127456","DOI":"10.1080\/19490976.2022.2127456","article-title":"Bifidobacterium spp. and their metabolite lactate protect against acute pancreatitis via inhibition of pancreatic and systemic inflammatory responses","volume":"14","author":"Li","year":"2022","journal-title":"Gut Microbes"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1174800","DOI":"10.3389\/fmicb.2023.1174800","article-title":"Bifidobacterium: a probiotic for the prevention and treatment of depression","volume":"14","author":"Li","year":"2023","journal-title":"Front. Microbiol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.7150\/thno.92350","article-title":"Bifidobacterium breve-derived indole-3-lactic acid ameliorates colitis-associated tumorigenesis by directing the differentiation of immature colonic macrophages","volume":"14","author":"Li","year":"2024","journal-title":"Theranostics"},{"key":"B21","doi-asserted-by":"publisher","first-page":"1212742","DOI":"10.3389\/fphar.2023.1212742","article-title":"Harnessing the potential of probiotics in the treatment of alcoholic liver disorders","volume":"14","author":"Mishra","year":"2023","journal-title":"Front. Pharmacol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"12060824","DOI":"10.3390\/biom12060824","article-title":"NAFLD: mechanisms, treatments, and biomarkers","volume":"12","author":"Nassir","year":"2022","journal-title":"Biomolecules"},{"key":"B23","doi-asserted-by":"publisher","first-page":"720","DOI":"10.1016\/j.jhep.2014.10.039","article-title":"Molecular mechanism of PPARalpha action and its impact on lipid metabolism, inflammation and fibrosis in non-alcoholic fatty liver disease","volume":"62","author":"Pawlak","year":"2015","journal-title":"J. Hepatol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.2741\/4892","article-title":"Current treatment paradigms and emerging therapies for NAFLD\/NASH","volume":"26","author":"Raza","year":"2021","journal-title":"Front. Biosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1087260","DOI":"10.3389\/fendo.2022.1087260","article-title":"Advancements in the treatment of non-alcoholic fatty liver disease (NAFLD)","volume":"13","author":"Rong","year":"2022","journal-title":"Front. Endocrinol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s13105-022-00878-5","article-title":"Antifibrogenic and apoptotic effects of ocoxin in cultured rat hepatic stellate cells","volume":"79","author":"Ruiz de Galarreta","year":"2023","journal-title":"J. Physiol. Biochem"},{"key":"B27","doi-asserted-by":"publisher","first-page":"505878","DOI":"10.1155\/2015\/505878","article-title":"The role of probiotic lactic acid bacteria and bifidobacteria in the prevention and treatment of inflammatory bowel disease and other related diseases: a systematic review of randomized human clinical trials","volume":"2015","author":"Saez-Lara","year":"2015","journal-title":"Biomed. Res. Int"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1513","DOI":"10.1172\/JCI131190","article-title":"Glycerol-3-phosphate is an FGF23 regulator derived from the injured kidney","volume":"130","author":"Simic","year":"2020","journal-title":"J. Clin. Invest"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/nature07976","article-title":"Autophagy regulates lipid metabolism","volume":"458","author":"Singh","year":"2009","journal-title":"Nature"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1700","DOI":"10.1016\/j.cmet.2022.09.017","article-title":"Gut-liver axis: pathophysiological concepts and clinical implications","volume":"34","author":"Tilg","year":"2022","journal-title":"Cell Metab"},{"key":"B31","doi-asserted-by":"publisher","first-page":"12010056","DOI":"10.3390\/biom12010056","article-title":"Understanding the role of the gut microbiome and microbial metabolites in non-alcoholic fatty liver disease: current evidence and perspectives","volume":"12","author":"Vallianou","year":"2021","journal-title":"Biomolecules"},{"key":"B32","doi-asserted-by":"publisher","first-page":"6489012","DOI":"10.1155\/2016\/6489012","article-title":"Role of NLRP3 inflammasome in the progression of NAFLD to NASH","volume":"2016","author":"Wan","year":"2016","journal-title":"Can. J. Gastroenterol. Hepatol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"4137","DOI":"10.1016\/j.cell.2021.06.019","article-title":"Gut-microbiota-targeted diets modulate human immune status","volume":"184","author":"Wastyk","year":"2021","journal-title":"Cell"},{"key":"B34","doi-asserted-by":"publisher","first-page":"5122655","DOI":"10.3390\/nu15122655","article-title":"Lactiplantibacillus plantarum OLL2712 induces autophagy via MYD88 and strengthens tight junction integrity to promote the barrier function in intestinal epithelial cells","volume":"15","author":"Watanabe-Yasuoka","year":"2023","journal-title":"Nutrients"},{"key":"B35","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1038\/s42255-023-00801-2","article-title":"Itaconic acid underpins hepatocyte lipid metabolism in non-alcoholic fatty liver disease in male mice","volume":"5","author":"Weiss","year":"2023","journal-title":"Nat. Metab"},{"key":"B36","doi-asserted-by":"publisher","first-page":"24399","DOI":"10.1038\/srep24399","article-title":"A pharmacological inhibitor of NLRP3 inflammasome prevents non-alcoholic fatty liver disease in a mouse model induced by high fat diet","volume":"6","author":"Yang","year":"2016","journal-title":"Sci. Rep"},{"key":"B37","doi-asserted-by":"publisher","first-page":"1303","DOI":"10.1056\/NEJMoa2118191","article-title":"Endovascular therapy for acute stroke with a large ischemic region","volume":"386","author":"Yoshimura","year":"2022","journal-title":"N. Engl. J. Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"851267","DOI":"10.3389\/fphar.2022.851267","article-title":"Protective effects of tiaoganquzhi decoction in treating inflammatory injury of nonalcoholic fatty liver disease by promoting CGI-58 and inhibiting expression of NLRP3 inflammasome","volume":"13","author":"Zhang","year":"2022","journal-title":"Front. Pharmacol"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1518150\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,7]],"date-time":"2025-01-07T07:06:07Z","timestamp":1736233567000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2024.1518150\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,7]]},"references-count":38,"alternative-id":["10.3389\/fmicb.2024.1518150"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2024.1518150","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,7]]},"article-number":"1518150"}}