{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T19:13:25Z","timestamp":1785352405247,"version":"3.55.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T00:00:00Z","timestamp":1708905600000},"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>Alcoholic-associated liver diseases (ALD) are now widespread issues worldwide. Alcoholic-induced chronic dysbiosis of the gut microbiota is one of the factors in the pathophysiology of ALD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this work, we employed a chronic-binge ethanol feeding mice model, as described in a previous report.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our findings demonstrate that hepatic inflammatory injury damage and accumulation of fat can be effectively reduced in mice with ALD by altering the gut microbiota utilizing <jats:italic>Bacillus coagulans<\/jats:italic>. Treatment with <jats:italic>B. coagulans<\/jats:italic> significantly modulates the levels of TNF-\u03b1, IL-1\u03b2, and IL-22 cytokines while maintaining tight junction proteins and mucin protein expressions to support intestinal barrier function restoration. Treatment with <jats:italic>B. coagulans<\/jats:italic> also alters the composition of the gut microbiota and increases the production of short-chain fatty acids (SCFAs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>This is mostly due to <jats:italic>B. coagulans<\/jats:italic> promotes the growth of bacteria that produce SCFAs, such as <jats:italic>Ruminococcus<\/jats:italic> species and <jats:italic>Akkermansia<\/jats:italic>, while inhibiting the growth of pathogenic bacteria like <jats:italic>Escherichia Shigella<\/jats:italic>. Moreover, treatment with <jats:italic>B. coagulans<\/jats:italic> causes levels of <jats:italic>2-Ketobutyric acid<\/jats:italic>, <jats:italic>ketoleucine<\/jats:italic>, and <jats:italic>indoleacetic acid<\/jats:italic> increase while <jats:italic>homovanillic acid<\/jats:italic> and <jats:italic>3\u2019-O-Methylguanosine<\/jats:italic> metabolites decrease significantly. This study facilitates the development of therapeutic and preventive strategies for ALD using lactic acid bacteria.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2024.1337185","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T10:21:35Z","timestamp":1711448495000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Bacillus coagulans regulates gut microbiota and ameliorates the alcoholic-associated liver disease in mice"],"prefix":"10.3389","volume":"15","author":[{"given":"Zhenzhen","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenting","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yurong","family":"Fan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,26]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"800","DOI":"10.1016\/j.ijbiomac.2015.06.005","article-title":"Bacteriocinogenic potential of a probiotic strain Bacillus coagulans [BDU3] from Ngari","volume":"79","author":"Abdhul","year":"2015","journal-title":"Int. J. Biol. Macromol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1002\/hep.31046","article-title":"An open-label, dose-escalation study to assess the safety and efficacy of IL-22 agonist F-652 in patients with alcohol-associated hepatitis","volume":"72","author":"Arab","year":"2020","journal-title":"Hepatology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/nprot.2013.032","article-title":"Mouse model of chronic and binge ethanol feeding (the NIAAA model)","volume":"8","author":"Bertola","year":"2013","journal-title":"Nat. Protoc."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"17756","DOI":"10.3748\/wjg.v20.i47.17756","article-title":"Pathogenesis of alcoholic liver disease: role of oxidative metabolism","volume":"20","author":"Ceni","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"947382","DOI":"10.3389\/fcimb.2022.947382","article-title":"The gut microbiota: a novel player in autoimmune hepatitis","volume":"12","author":"Cheng","year":"2022","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1097\/CLD.0000000000000033","article-title":"Pharmacotherapy options for alcohol use disorder in patients with alcohol-associated liver disease: a brief guide for clinicians","volume":"21","author":"Coe","year":"2023","journal-title":"Clin. Liver Dis."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/s41586-019-1742-x","article-title":"Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease","volume":"575","author":"Duan","year":"2019","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"3735","DOI":"10.3390\/ijms24043735","article-title":"Alcohol, inflammation, and microbiota in alcoholic liver disease","volume":"24","author":"Duki\u0107","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1490","DOI":"10.3389\/fmicb.2017.01490","article-title":"Bacillus as potential probiotics: status, concerns, and future perspectives","volume":"8","author":"Elshaghabee","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.jhep.2018.10.023","article-title":"Inflammatory pathways in alcoholic steatohepatitis","volume":"70","author":"Gao","year":"2019","journal-title":"J. Hepatol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1015","DOI":"10.1016\/S0140-6736(18)31310-2","article-title":"Alcohol use and burden for 195 countries and territories, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016","volume":"392","year":"2018","journal-title":"Lancet"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"891","DOI":"10.1136\/gutjnl-2016-313432","article-title":"Recovery of ethanol-induced Akkermansia muciniphila depletion ameliorates alcoholic liver disease","volume":"67","author":"Grander","year":"2018","journal-title":"Gut"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/9097276","article-title":"Probiotics for alleviating alcoholic liver injury","volume":"2019","author":"Gu","year":"2019","journal-title":"Gastroenterol. Res. Pract."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"Cd006895","DOI":"10.1002\/14651858.CD006895.pub3","article-title":"Probiotics for preventing acute upper respiratory tract infections","volume":"2015","author":"Hao","year":"2015","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1002\/hep.26321","article-title":"Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice","volume":"58","author":"Hartmann","year":"2013","journal-title":"Hepatology"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1504","DOI":"10.1136\/gutjnl-2018-317232","article-title":"Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice","volume":"68","author":"Hendrikx","year":"2019","journal-title":"Gut"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"719","DOI":"10.1038\/s41579-023-00904-3","article-title":"The gut-liver axis and gut microbiota in health and liver disease","volume":"21","author":"Hsu","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1002\/hep.23837","article-title":"Interleukin-22 treatment ameliorates alcoholic liver injury in a murine model of chronic-binge ethanol feeding: role of signal transducer and activator of transcription 3","volume":"52","author":"Ki","year":"2010","journal-title":"Hepatology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1016\/j.jhep.2018.12.003","article-title":"Fibrosis and alcohol-related liver disease","volume":"70","author":"Lackner","year":"2019","journal-title":"J. Hepatol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/nm.4102","article-title":"CARD9 impacts colitis by altering gut microbiota metabolism of tryptophan into aryl hydrocarbon receptor ligands","volume":"22","author":"Lamas","year":"2016","journal-title":"Nat. Med."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"e0064122","DOI":"10.1128\/spectrum.00641-22","article-title":"Bacillus coagulans in combination with chitooligosaccharides regulates gut microbiota and ameliorates the DSS-induced colitis in mice","volume":"10","author":"Liu","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"830","DOI":"10.1136\/gutjnl-2015-310585","article-title":"Intestinal microbiota contributes to individual susceptibility to alcoholic liver disease","volume":"65","author":"Llopis","year":"2016","journal-title":"Gut"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1038\/s41467-017-00796-x","article-title":"Gastric acid suppression promotes alcoholic liver disease by inducing overgrowth of intestinal Enterococcus","volume":"8","author":"Llorente","year":"2017","journal-title":"Nat. Commun."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"309","DOI":"10.3390\/metabo12040309","article-title":"Untargeted metabolomics reveals metabolic stress alleviation by prepartum exercise in transition dairy cows","volume":"12","author":"Luo","year":"2022","journal-title":"Meta"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1038\/ajg.2015.313","article-title":"Clinical and pathophysiological consequences of alterations in the microbiome in cirrhosis","volume":"110","author":"Macnaughtan","year":"2015","journal-title":"Am. J. Gastroenterol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1017\/S0029665120006916","article-title":"SCFA: mechanisms and functional importance in the gut","volume":"80","author":"Martin-Gallausiaux","year":"2021","journal-title":"Proc. Nutr. Soc."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1002\/hep.26336","article-title":"Therapeutic potential of interleukin 1 inhibitors in the treatment of alcoholic liver disease","volume":"57","author":"Mathews","year":"2013","journal-title":"Hepatology"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1334","DOI":"10.1111\/jam.13690","article-title":"Bacillus probiotics: an alternative to antibiotics for livestock production","volume":"124","author":"Mingmongkolchai","year":"2018","journal-title":"J. Appl. Microbiol."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"679","DOI":"10.3920\/BM2019.0016","article-title":"Bacillus coagulans and its applications in medicine","volume":"10","author":"Mu","year":"2019","journal-title":"Benef Microbes"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"G966","DOI":"10.1152\/ajpgi.00380.2011","article-title":"Colonic microbiome is altered in alcoholism","volume":"302","author":"Mutlu","year":"2012","journal-title":"Am. J. Physiol. Gastrointest. 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J. Mol. Sci."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1574-6941.2007.00375.x","article-title":"Multivariate analyses in microbial ecology","volume":"62","author":"Ramette","year":"2007","journal-title":"FEMS Microbiol. Ecol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"R60","DOI":"10.1186\/gb-2011-12-6-r60","article-title":"Metagenomic biomarker discovery and explanation","volume":"12","author":"Segata","year":"2011","journal-title":"Genome Biol."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"108918","DOI":"10.1016\/j.cbi.2019.108918","article-title":"The role of cytochrome P4502E1 in the pathogenesis of alcoholic liver disease and carcinogenesis","volume":"316","author":"Seitz","year":"2020","journal-title":"Chem. Biol. Interact."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1038\/s41572-018-0014-7","article-title":"Alcoholic liver disease","volume":"4","author":"Seitz","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"3669","DOI":"10.1007\/s00394-020-02200-9","article-title":"Synbiotic supplementation with prebiotic green banana resistant starch and probiotic Bacillus coagulans spores ameliorates gut inflammation in mouse model of inflammatory bowel diseases","volume":"59","author":"Shinde","year":"2020","journal-title":"Eur. J. Nutr."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"818","DOI":"10.3390\/nu11040818","article-title":"Synbiotic supplementation containing whole plant sugar cane fibre and probiotic spores potentiates protective synergistic effects in mouse model of IBD","volume":"11","author":"Shinde","year":"2019","journal-title":"Nutrients"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.jff.2018.10.031","article-title":"Probiotic Bacillus coagulans MTCC 5856 spores exhibit excellent in-vitro functional efficacy in simulated gastric survival, mucosal adhesion and immunomodulation","volume":"52","author":"Shinde","year":"2019","journal-title":"J. Funct. Foods"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1038\/ajg.2017.469","article-title":"ACG clinical guideline: alcoholic liver disease","volume":"113","author":"Singal","year":"2018","journal-title":"Am. J. Gastroenterol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1021\/ac051437y","article-title":"XCMS: processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification","volume":"78","author":"Smith","year":"2006","journal-title":"Anal. Chem."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"1830693","DOI":"10.1080\/19490976.2020.1830693","article-title":"Therapeutic manipulation of gut microbiota by polysaccharides of Wolfiporia cocos reveals the contribution of the gut fungi-induced PGE2 to alcoholic hepatic steatosis","volume":"12","author":"Sun","year":"2020","journal-title":"Gut Microbes"},{"key":"ref45","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1080\/14656566.2018.1465929","article-title":"Alcoholic steatohepatitis (ASH) and alcoholic hepatitis (AH): cascade of events, clinical aspects, and pharmacotherapy options","volume":"19","author":"Teschke","year":"2018","journal-title":"Expert. Opin. Pharmacother."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1002\/hep.28456","article-title":"Interleukin-1 and inflammasomes in alcoholic liver disease\/acute alcoholic hepatitis and nonalcoholic fatty liver disease\/nonalcoholic steatohepatitis","volume":"64","author":"Tilg","year":"2016","journal-title":"Hepatology"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.3389\/fmicb.2016.01144","article-title":"Gut microbiota profiling: metabolomics based approach to unravel compounds affecting human health","volume":"7","author":"Vernocchi","year":"2016","journal-title":"Front. Microbiol."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.chom.2016.01.003","article-title":"Intestinal REG3 lectins protect against alcoholic steatohepatitis by reducing mucosa-associated microbiota and preventing bacterial translocation","volume":"19","author":"Wang","year":"2016","journal-title":"Cell Host Microbe"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1038\/s41423-020-00579-3","article-title":"Immunological mechanisms and therapeutic targets of fatty liver diseases","volume":"18","author":"Wang","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1007\/s11306-016-1050-5","article-title":"Serum metabolomics for early diagnosis of esophageal squamous cell carcinoma by UHPLC-QTOF\/MS","volume":"12","author":"Wang","year":"2016","journal-title":"Metabolomics"},{"key":"ref51","volume-title":"Global status report on alcohol and health 2018","year":"2018"},{"key":"ref52","doi-asserted-by":"publisher","first-page":"1299","DOI":"10.1136\/gutjnl-2020-321565","article-title":"Microbiota tryptophan metabolism induces aryl hydrocarbon receptor activation and improves alcohol-induced liver injury","volume":"70","author":"Wrzosek","year":"2021","journal-title":"Gut"},{"key":"ref53","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1146\/annurev-pathmechdis-031521-030435","article-title":"Recent advances in understanding of pathogenesis of alcohol-associated liver disease","volume":"18","author":"Wu","year":"2023","journal-title":"Annu. Rev. Pathol."},{"key":"ref54","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1002\/hep.24018","article-title":"Enteric dysbiosis associated with a mouse model of alcoholic liver disease","volume":"53","author":"Yan","year":"2011","journal-title":"Hepatology"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1038\/nm1720","article-title":"Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens","volume":"14","author":"Zheng","year":"2008","journal-title":"Nat. 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