{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T18:50:10Z","timestamp":1786560610101,"version":"build-2736575974"},"reference-count":117,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T00:00:00Z","timestamp":1740441600000},"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. Immunol."],"abstract":"<jats:p>The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1526967","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T06:54:01Z","timestamp":1740466441000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":18,"title":["Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Siqi","family":"Ren","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinping","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahong","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zijun","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sipeng","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuai","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingxing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fukuan","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yueshui","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobing","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhangang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11550","article-title":"Diversity, stability and resilience of the human gut microbiota","volume":"489","author":"Lozupone","year":"2012","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-017-0563-2","article-title":"Gut microbial balance and liver transplantation: alteration, management, and prediction","volume":"12","author":"Tian","year":"2018","journal-title":"Front Med"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e0247039","DOI":"10.1371\/journal.pone.0247039","article-title":"Association between physical activity and changes in intestinal microbiota composition: A systematic review","volume":"16","author":"Aya","year":"2021","journal-title":"PloS One"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-010-0093-z","article-title":"Human gut microbiome: the second genome of human body","volume":"1","author":"Zhu","year":"2010","journal-title":"Protein Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.k2179","article-title":"Role of the gut microbiota in nutrition and health","volume":"361","author":"Valdes","year":"2018","journal-title":"BMJ (Clin Res ed)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1111\/1462-2920.13589","article-title":"Formation of propionate and butyrate by the human colonic microbiota","volume":"19","author":"Louis","year":"2017","journal-title":"Environ Microbiol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.003","article-title":"Gut microbiota regulation of tryptophan metabolism in health and disease","volume":"23","author":"Agus","year":"2018","journal-title":"Cell Host Microbe"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3390\/cells12050793","article-title":"Gut-microbiota-derived metabolites maintain gut and systemic immune homeostasis","volume":"12","author":"Wang","year":"2023","journal-title":"Cells"},{"key":"B9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s40168-022-01452-3","article-title":"Gut microbiota-derived metabolites mediate the neuroprotective effect of melatonin in cognitive impairment induced by sleep deprivation","volume":"11","author":"Wang","year":"2023","journal-title":"Microbiome"},{"key":"B10","doi-asserted-by":"publisher","first-page":"943","DOI":"10.1016\/j.cmet.2023.04.015","article-title":"Lactobacillus plantarum-derived indole-3-lactic acid ameliorates colorectal tumorigenesis via epigenetic regulation of CD8(+) T cell immunity","volume":"35","author":"Zhang","year":"2023","journal-title":"Cell Metab"},{"key":"B11","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1186\/s40168-023-01551-9","article-title":"Gut microbiota-derived 3-phenylpropionic acid promotes intestinal epithelial barrier function via AhR signaling","volume":"11","author":"Hu","year":"2023","journal-title":"Microbiome"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.113810","article-title":"Gut microbiota: A new insight into lung diseases","volume":"155","author":"Ma","year":"2022","journal-title":"Biomed Pharmacother"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/nu13082660","article-title":"Effects of probiotic NVP-1704 on mental health and sleep in healthy adults: an 8-week randomized, double-blind, placebo-controlled trial","volume":"13","author":"Lee","year":"2021","journal-title":"Nutrients"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-023-00874-w","article-title":"Early-life interactions between the microbiota and immune system: impact on immune system development and atopic disease","volume":"23","author":"Donald","year":"2023","journal-title":"Nat Rev Immunol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat Rev Dis Primers"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1430991","article-title":"New advances in the treatment of intermediate and advanced hepatocellular carcinoma","volume":"14","author":"Zhonghao","year":"2024","journal-title":"Front Oncol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1021\/acsptsci.3c00216","article-title":"Role of immunological cells in hepatocellular carcinoma disease and associated pathways","volume":"6","author":"Aasarey","year":"2023","journal-title":"ACS Pharmacol Trans Sci"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e44582","DOI":"10.7759\/cureus.44582","article-title":"Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immunotherapy: A promising breakthrough in cancer therapeutics","volume":"15","author":"Abaza","year":"2023","journal-title":"Cureus"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/01635581.2024.2415136","article-title":"Alterations of nutrient elements in hepatocellular carcinoma patients treated with atezolizumab-bevacizumab","volume":"77","author":"Xiao","year":"2024","journal-title":"Nutr Cancer"},{"key":"B20","doi-asserted-by":"publisher","first-page":"746","DOI":"10.3390\/v12070746","article-title":"The multiple roles of hepatitis B virus X protein (HBx) dysregulated microRNA in hepatitis B virus-associated hepatocellular carcinoma (HBV-HCC) and immune pathways","volume":"12","author":"Sartorius","year":"2020","journal-title":"Viruses"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2023.01.001","article-title":"Chronic hepatitis C: advances in therapy and the remaining challenges","volume":"107","author":"Alqahtani","year":"2023","journal-title":"Med Clinics North America"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1177\/20420188231160389","article-title":"Should we undertake surveillance for HCC in patients with MAFLD","volume":"14","author":"Norero","year":"2023","journal-title":"Ther Adv Endocrinol Metab"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.07.022","article-title":"Estimate of hepatocellular carcinoma incidence in patients with alcoholic cirrhosis","volume":"69","author":"Ganne-Carri\u00e9","year":"2018","journal-title":"J Hepatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(21)01374-x","article-title":"Liver cirrhosis","volume":"398","author":"Gin\u00e8s","year":"2021","journal-title":"Lancet (London England)"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.978110","article-title":"Association between sarcopenia and prognosis of hepatocellular carcinoma: A systematic review and meta-analysis","volume":"9","author":"Jiang","year":"2022","journal-title":"Front Nutr"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2024.1429242","article-title":"Changes in the gut microbiota of patients with sarcopenia based on 16S rRNA gene sequencing: a systematic review and meta-analysis","volume":"11","author":"Song","year":"2024","journal-title":"Front Nutr"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1111\/1751-7915.13410","article-title":"Akkermansia muciniphila is a promising probiotic","volume":"12","author":"Zhang","year":"2019","journal-title":"Microbial Biotechnol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"3964","DOI":"10.1038\/s41467-022-31312-5","article-title":"Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment","volume":"13","author":"Schneider","year":"2022","journal-title":"Nat Commun"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1093\/jaoac\/87.3.727","article-title":"Applications and uses of resistant starch","volume":"87","author":"Brown","year":"2004","journal-title":"J AOAC Int"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1016\/j.cmet.2023.08.002","article-title":"Resistant starch decreases intrahepatic triglycerides in patients with NAFLD via gut microbiome alterations","volume":"35","author":"Ni","year":"2023","journal-title":"Cell Metab"},{"key":"B31","doi-asserted-by":"publisher","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":"B32","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1186\/s40168-021-01125-7","article-title":"Commensal microbe-derived acetate suppresses NAFLD\/NASH development via hepatic FFAR2 signalling in mice","volume":"9","author":"Aoki","year":"2021","journal-title":"Microbiome"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1159\/000521358","article-title":"The gut microbiome and hepatocellular carcinoma: implications for early diagnostic biomarkers and novel therapies","volume":"11","author":"Kang","year":"2022","journal-title":"Liver Cancer"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.2001.81.3.1031","article-title":"Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides","volume":"81","author":"Topping","year":"2001","journal-title":"Physiol Rev"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173086","article-title":"Valeric acid lowers arterial blood pressure in rats","volume":"877","author":"Onyszkiewicz","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1097\/hep.0000000000000047","article-title":"Gut microbial metabolite butyrate improves anticancer therapy by regulating intracellular calcium homeostasis","volume":"78","author":"Che","year":"2023","journal-title":"Hepatol (Baltimore Md)"},{"key":"B37","doi-asserted-by":"publisher","first-page":"e2203894119","DOI":"10.1073\/pnas.2203894119","article-title":"Gut flora disequilibrium promotes the initiation of liver cancer by modulating tryptophan metabolism and up-regulating SREBP2","volume":"119","author":"Chen","year":"2022","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B38","doi-asserted-by":"publisher","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":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2023.104952","article-title":"Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid","volume":"100","author":"Lau","year":"2024","journal-title":"EBioMedicine"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.129917","article-title":"EChinacea purpurea polysaccharide intervene in hepatocellular carcinoma via modulation of gut microbiota to inhibit TLR4\/NF-\u03baB pathway","volume":"261","author":"Jing","year":"2024","journal-title":"Int J Biol Macromolecules"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.007","article-title":"Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4","volume":"21","author":"Dapito","year":"2012","journal-title":"Cancer Cell"},{"key":"B42","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/j.ccell.2023.02.016","article-title":"The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth","volume":"41","author":"de Visser","year":"2023","journal-title":"Cancer Cell"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2019.11.009","article-title":"Immune cells within the tumor microenvironment: Biological functions and roles in cancer immunotherapy","volume":"470","author":"Lei","year":"2020","journal-title":"Cancer Lett"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.840610","article-title":"T cell metabolism in infection","volume":"13","author":"Wik","year":"2022","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867189","article-title":"The era of cytotoxic CD4 T cells","volume":"13","author":"Cenerenti","year":"2022","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.1992.tb00662.x","article-title":"Human Th1 and Th2 lymphocytes: their role in the pathophysiology of atopy","volume":"47","author":"Del Prete","year":"1992","journal-title":"Allergy"},{"key":"B47","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1007\/s12032-022-01888-5","article-title":"Role of NKT cells in cancer immunotherapy-from bench to bed","volume":"40","author":"Bayatipoor","year":"2022","journal-title":"Med Oncol (Northwood London England)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0495-2","article-title":"Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study","volume":"25","author":"Depommier","year":"2019","journal-title":"Nat Med"},{"key":"B49","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1186\/s12943-020-01238-x","article-title":"Natural killer cells in cancer biology and therapy","volume":"19","author":"Wu","year":"2020","journal-title":"Mol Cancer"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.879452","article-title":"A phase I study of locoregional high-dose autologous natural killer cell therapy with hepatic arterial infusion chemotherapy in patients with locally advanced hepatocellular carcinoma","volume":"13","author":"Bae","year":"2022","journal-title":"Front Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1016\/bs.podrm.2018.11.003","article-title":"Sorafenib","volume":"44","author":"Abdelgalil","year":"2019","journal-title":"Profiles Drug Substances Excipients Related Methodol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2021.105226","article-title":"Increased effects of 2,5-dimethylcelecoxib on sensitivity of hepatocellular carcinoma cells to sorafenib via CYP3A5 expression and activation of AMPK","volume":"76","author":"Chen","year":"2021","journal-title":"Toxicol Vitro: An Int J Published Assoc BIBRA"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2023-006817","article-title":"2,5-dimethylcelecoxib alleviated NK and T-cell exhaustion in hepatocellular carcinoma via the gastrointestinal microbiota-AMPK-mTOR axis","volume":"11","author":"Pan","year":"2023","journal-title":"J Immunother Cancer"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33885","article-title":"Prediagnostic alterations in circulating bile acid profiles in the development of hepatocellular carcinoma","volume":"150","author":"Stepien","year":"2022","journal-title":"Int J Cancer"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/bs.ircmb.2019.07.004","article-title":"Dendritic cell subsets and locations","volume":"348","author":"Balan","year":"2019","journal-title":"Int Rev Cell Mol Biol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24044253","article-title":"Dendritic cell and cancer therapy","volume":"24","author":"Galati","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14184380","article-title":"Dendritic-cell-vaccine-based immunotherapy for hepatocellular carcinoma: clinical trials and recent preclinical studies","volume":"14","author":"Jeng","year":"2022","journal-title":"Cancers"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22626","article-title":"A phase II study of adoptive immunotherapy using dendritic cells pulsed with tumor lysate in patients with hepatocellular carcinoma","volume":"49","author":"Palmer","year":"2009","journal-title":"Hepatol (Baltimore Md)"},{"key":"B59","doi-asserted-by":"publisher","first-page":"815","DOI":"10.1186\/s12967-023-04716-0","article-title":"Macrophage metabolism, phenotype, function, and therapy in hepatocellular carcinoma (HCC)","volume":"21","author":"Huang","year":"2023","journal-title":"J Trans Med"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Shapouri-Moghaddam","year":"2018","journal-title":"J Cell Physiol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1002\/path.4133","article-title":"Macrophage plasticity and polarization in tissue repair and remodelling","volume":"229","author":"Mantovani","year":"2013","journal-title":"J Pathol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2016.01.004","article-title":"The nature of myeloid-derived suppressor cells in the tumor microenvironment","volume":"37","author":"Kumar","year":"2016","journal-title":"Trends Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1126\/science.1110591","article-title":"Diversity of the human intestinal microbial flora","volume":"308","author":"Eckburg","year":"2005","journal-title":"Sci (New York NY)"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2008.09.007","article-title":"Mucosal glycan foraging enhances fitness and transmission of a saccharolytic human gut bacterial symbiont","volume":"4","author":"Martens","year":"2008","journal-title":"Cell Host Microbe"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2111228119","article-title":"Bacteroides thetaiotaomicron uses a widespread extracellular DNase to promote bile-dependent biofilm formation","volume":"119","author":"B\u00e9chon","year":"2022","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2297846","article-title":"B. thetaiotaomicron-derived acetic acid modulate immune microenvironment and tumor growth in hepatocellular carcinoma","volume":"16","author":"Ma","year":"2024","journal-title":"Gut Microbes"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1007\/s00449-013-0965-8","article-title":"D-Lactic acid biosynthesis from biomass-derived sugars via Lactobacillus delbrueckii fermentation","volume":"36","author":"Zhang","year":"2013","journal-title":"Bioprocess Biosyst Engineering"},{"key":"B68","doi-asserted-by":"publisher","first-page":"eadg2697","DOI":"10.1126\/sciadv.adg2697","article-title":"d-lactate modulates M2 tumor-associated macrophages and remodels immunosuppressive tumor microenvironment for hepatocellular carcinoma","volume":"9","author":"Han","year":"2023","journal-title":"Sci Advances"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241411387","article-title":"Potential effects of regulating intestinal flora on immunotherapy for liver cancer","volume":"24","author":"Yan","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13081949","article-title":"Recent advances and future prospects in immune checkpoint (ICI)-based combination therapy for advanced HCC","volume":"13","author":"Dong","year":"2021","journal-title":"Cancers"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-004779","article-title":"Gut microbiota and metabolites associate with outcomes of immune checkpoint inhibitor-treated unresectable hepatocellular carcinoma","volume":"10","author":"Lee","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B72","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1038\/s41467-022-28744-4","article-title":"Microalgae-based oral microcarriers for gut microbiota homeostasis and intestinal protection in cancer radiotherapy","volume":"13","author":"Zhang","year":"2022","journal-title":"Nat Commun"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201609-1848OC","article-title":"The timing of early antibiotics and hospital mortality in sepsis","volume":"196","author":"Liu","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1128\/aac.00635-18","article-title":"Systematic review and meta-analysis of the efficacy of short-course antibiotic treatments for community-acquired pneumonia in adults","volume":"62","author":"Tansarli","year":"2018","journal-title":"Antimicrobial Agents Chemother"},{"key":"B75","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1186\/s40001-023-01399-7","article-title":"Effect of antibiotic prophylaxis in the prognosis of Post-neurosurgical meningitis patients","volume":"28","author":"Zheng","year":"2023","journal-title":"Eur J Med Res"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1016\/j.cllc.2022.09.005","article-title":"Antibiotic prescriptions in lung cancer and melanoma populations: differences with potential clinical implications in the immunotherapy era","volume":"24","author":"Gonugunta","year":"2023","journal-title":"Clin Lung Cancer"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1159\/000518090","article-title":"Use of antibiotics during immune checkpoint inhibitor treatment is associated with lower survival in hepatocellular carcinoma","volume":"10","author":"Cheung","year":"2021","journal-title":"Liver Cancer"},{"key":"B78","doi-asserted-by":"publisher","first-page":"e0281459","DOI":"10.1371\/journal.pone.0281459","article-title":"Pretreatment with antibiotics is associated with reduced therapeutic response to atezolizumab plus bevacizumab in patients with hepatocellular carcinoma","volume":"18","author":"Maesaka","year":"2023","journal-title":"PloS One"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1159\/000519108","article-title":"Early\u00a0antibiotic exposure is not detrimental to therapeutic effect from immunotherapy in hepatocellular carcinoma","volume":"10","author":"Fessas","year":"2021","journal-title":"Liver Cancer"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23845","article-title":"Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents","volume":"52","author":"Yu","year":"2010","journal-title":"Hepatol (Baltimore Md)"},{"key":"B81","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1186\/s13046-019-1271-3","article-title":"Intestinal dysbacteriosis-induced IL-25 promotes development of HCC via alternative activation of macrophages in tumor microenvironment","volume":"38","author":"Li","year":"2019","journal-title":"J Exp Clin Cancer Res: CR"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan5931","article-title":"Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells","volume":"360","author":"Ma","year":"2018","journal-title":"Sci (New York NY)"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1179\/joc.2010.22.6.373","article-title":"Microbiological evaluation of commercial probiotic products available in the USA in 2009","volume":"22","author":"Drago","year":"2010","journal-title":"J Chemother (Florence Italy)"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.048975-0","article-title":"Probiotics in colorectal cancer (CRC) with emphasis on mechanisms of action and current perspectives","volume":"62","author":"Kahouli","year":"2013","journal-title":"J Med Microbiol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01694-6","article-title":"Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial","volume":"28","author":"Dizman","year":"2022","journal-title":"Nat Med"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz7015","article-title":"Dietary fiber and probiotics influence the gut microbiome and melanoma immunotherapy response","volume":"374","author":"Spencer","year":"2021","journal-title":"Sci (New York NY)"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1007\/s00268-021-06388-7","article-title":"Influence of probiotics administration before liver resection in patients with liver disease: A randomized controlled trial","volume":"46","author":"Roussel","year":"2022","journal-title":"World J Surgery"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052606","article-title":"Mechanisms by which probiotic bacteria attenuate the risk of hepatocellular carcinoma","volume":"22","author":"Thilakarathna","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.4254\/wjh.v14.i2.372","article-title":"Immunomodulation by probiotics and prebiotics in hepatocellular carcinoma","volume":"14","author":"Russo","year":"2022","journal-title":"World J Hepatol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.gene.2011.09.003","article-title":"Effect of probiotic fermented milk and chlorophyllin on gene expressions and genotoxicity during AFB1-induced hepatocellular carcinoma","volume":"490","author":"Kumar","year":"2011","journal-title":"Gene"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1518189113","article-title":"Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice","volume":"113","author":"Li","year":"2016","journal-title":"Proc Natl Acad Sci United States America"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12041683","article-title":"Research progress of fecal microbiota transplantation in liver diseases","volume":"12","author":"Zhao","year":"2023","journal-title":"J Clin Med"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2013.4","article-title":"Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections","volume":"108","author":"Surawicz","year":"2013","journal-title":"Am J Gastroenterol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1136\/bcr-2017-222310","article-title":"Healthy donor faecal transplant for corticosteroid non-responsive severe alcoholic hepatitis","volume":"2017","author":"Philips","year":"2017","journal-title":"BMJ Case Rep"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v27.i42.7340","article-title":"Gut microbiome composition can predict the response to nivolumab in advanced hepatocellular carcinoma patients","volume":"27","author":"Chung","year":"2021","journal-title":"World J Gastroenterol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1905","article-title":"Gut dysbiosis and fecal calprotectin predict response to immune checkpoint inhibitors in patients with hepatocellular carcinoma","volume":"6","author":"Ponziani","year":"2022","journal-title":"Hepatol Commun"},{"key":"B97","doi-asserted-by":"publisher","first-page":"225","DOI":"10.3390\/nu12010225","article-title":"Lactobacillus reuteri DSM 17938 and magnesium oxide in children with functional chronic constipation: A double-blind and randomized clinical trial","volume":"12","author":"Kubota","year":"2020","journal-title":"Nutrients"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10112203","article-title":"Lactobacillus reuteri MJM60668 Prevent Progression of Non-Alcoholic Fatty Liver Disease through Anti-Adipogenesis and Anti-inflammatory Pathway","volume":"10","author":"Werlinger","year":"2022","journal-title":"Microorganisms"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1039\/d0fo02879g","article-title":"Lactobacillus rhamnosus FJSYC4-1 and Lactobacillus reuteri FGSZY33L6 alleviate metabolic syndrome via gut microbiota regulation","volume":"12","author":"Zheng","year":"2021","journal-title":"Food Funct"},{"key":"B100","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1016\/j.cell.2023.03.011","article-title":"Dietary tryptophan metabolite released by intratumoral Lactobacillus reuteri facilitates immune checkpoint inhibitor treatment","volume":"186","author":"Bender","year":"2023","journal-title":"Cell"},{"key":"B101","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/hep.32449","article-title":"Gut microbiota-derived short-chain fatty acids regulate group 3 innate lymphoid cells in HCC","volume":"77","author":"Hu","year":"2023","journal-title":"Hepatol (Baltimore Md)"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2016.05.020","article-title":"Metabolic inflammation-associated IL-17A causes non-alcoholic steatohepatitis and hepatocellular carcinoma","volume":"30","author":"Gomes","year":"2016","journal-title":"Cancer Cell"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.23736\/s1121-421x.17.02374-1","article-title":"Fecal microbiota transplantation: past, present and future perspectives","volume":"63","author":"Bibb\u00f2","year":"2017","journal-title":"Minerva Gastroenterol E Dietol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/125.6.1401","article-title":"Dietary modulation of the human colonic microbiota: introducing the concept of prebiotics","volume":"125","author":"Gibson","year":"1995","journal-title":"J Nutr"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-021-11646-8","article-title":"Probiotics, prebiotics and synbiotics: Safe options for next-generation therapeutics","volume":"106","author":"Yadav","year":"2022","journal-title":"Appl Microbiol Biotechnol"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2009.06.001","article-title":"Gastrointestinal microflora, food components and colon cancer prevention","volume":"20","author":"Davis","year":"2009","journal-title":"J Nutr Biochem"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1111\/cas.12231","article-title":"Vegetable-based dietary pattern and liver cancer risk: results from the Shanghai women\u2019s and men\u2019s health studies","volume":"104","author":"Zhang","year":"2013","journal-title":"Cancer Sci"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.08.005","article-title":"Increased intake of vegetables, but not fruit, reduces risk for hepatocellular carcinoma: a meta-analysis","volume":"147","author":"Yang","year":"2014","journal-title":"Gastroenterology"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau5812","article-title":"The gut microbiota at the intersection of diet and human health","volume":"362","author":"Gentile","year":"2018","journal-title":"Sci (New York NY)"},{"key":"B110","doi-asserted-by":"publisher","first-page":"328","DOI":"10.1038\/s41398-021-01443-2","article-title":"A diet high in sugar and fat influences neurotransmitter metabolism and then affects brain function by altering the gut microbiota","volume":"11","author":"Guo","year":"2021","journal-title":"Trans Psychiatry"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2019-319664","article-title":"Dietary cholesterol drives fatty liver-associated liver cancer by modulating gut microbiota and metabolites","volume":"70","author":"Zhang","year":"2021","journal-title":"Gut"},{"key":"B112","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1016\/j.cell.2018.09.004","article-title":"Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer","volume":"175","author":"Singh","year":"2018","journal-title":"Cell"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2023.116945","article-title":"Enhancing NKT cell-mediated immunity against hepatocellular carcinoma: Role of XYXD in promoting primary bile acid synthesis and improving gut microbiota","volume":"318","author":"Deng","year":"2024","journal-title":"J Ethnopharmacol"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2023.08.052","article-title":"Traditional medicine pien tze huang suppresses colorectal tumorigenesis through restoring gut microbiota and metabolites","volume":"165","author":"Gou","year":"2023","journal-title":"Gastroenterology"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25189938","article-title":"Recent advances and mechanisms of phage-based therapies in cancer treatment","volume":"25","author":"Ooi","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B116","doi-asserted-by":"publisher","first-page":"3215","DOI":"10.1038\/s41467-023-39028-w","article-title":"Bacteriophage targeting microbiota alleviates non-alcoholic fatty liver disease induced by high alcohol-producing Klebsiella pneumoniae","volume":"14","author":"Gan","year":"2023","journal-title":"Nat Commun"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1038\/s41551-019-0423-2","article-title":"Phage-guided modulation of the gut microbiota of mouse models of colorectal cancer augments their responses to chemotherapy","volume":"3","author":"Zheng","year":"2019","journal-title":"Nat Biomed Engineering"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1526967\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T06:54:04Z","timestamp":1740466444000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1526967\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,25]]},"references-count":117,"alternative-id":["10.3389\/fimmu.2025.1526967"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1526967","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,25]]},"article-number":"1526967"}}