Unveiling the complex relationship between gut microbiota and liver cancer: opportunities for novel therapeutic interventions

References

• Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin. 2021;71(3):209–15. doi:10.3322/caac.21660.
   PubMed Web of Science ®Google Scholar
• Brar G, Greten TF, Graubard BI, McNeel TS, Petrick JL, McGlynn KA, Altekruse SF. Hepatocellular carcinoma survival by etiology: A SEER-Medicare database analysis. Hepatol Commun. 2020;4(10):1541–1551. doi:10.1002/hep4.1564.
   PubMed Web of Science ®Google Scholar
• Lubel JS, Roberts SK, Strasser SI, Thompson AJ, Philip J, Goodwin M, Clarke S, Crawford DH, Levy MT, Shackel N, et al. Australian recommendations for the management of hepatocellular carcinoma: a consensus statement. Med J Aust. 2021;214(10):475–483. doi:10.5694/mja2.50885.
   PubMed Web of Science ®Google Scholar
• Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastro Hepat. 2019;16(10):589–604. doi:10.1038/s41575-019-0186-y.
   PubMed Web of Science ®Google Scholar
• Refolo MG, Messa C, Guerra V, Carr BI, D’Alessandro R. Inflammatory mechanisms of HCC development. Cancers. 2020;12(3):641. doi:10.3390/cancers12030641.
   PubMed Web of Science ®Google Scholar
• Roderburg C, Luedde T. The role of the gut microbiome in the development and progression of liver cirrhosis and hepatocellular carcinoma. Gut Microbes. 2014;5(4):441–445. doi:10.4161/gmic.29599.
   PubMed Web of Science ®Google Scholar
• Shen S, Khatiwada S, Behary J, Kim R, Zekry A. Modulation of the gut microbiome to improve clinical outcomes in hepatocellular carcinoma. Cancers. 2022;14(9):2099. doi:10.3390/cancers14092099.
   PubMed Web of Science ®Google Scholar
• Behary J, Raposo AE, Amorim NML, Zheng H, Gong L, McGovern E, Chen J, Liu K, Beretov J, Theocharous C, et al. Defining the temporal evolution of gut dysbiosis and inflammatory responses leading to hepatocellular carcinoma in Mdr2 −/− mouse model. BMC Microbiol. 2021;21(1):113. doi:10.1186/s12866-021-02171-9.
   PubMed Web of Science ®Google Scholar
• Yu LCH. Microbiota dysbiosis and barrier dysfunction in inflammatory bowel disease and colorectal cancers: exploring a common ground hypothesis. J Biomed Sci. 2018;25(1):79. doi:10.1186/s12929-018-0483-8.
   PubMedGoogle Scholar
• Ram AK, Pottakat B, Vairappan B. Increased systemic zonula occludens 1 associated with inflammation and independent biomarker in patients with hepatocellular carcinoma. Bmc Cancer. 2018;18(1):572. doi:10.1186/s12885-018-4484-5.
   PubMedGoogle Scholar
• Behary J, Amorim N, Jiang X-T, Raposo A, Gong L, McGovern E, Ibrahim R, Chu F, Stephens C, Jebeili H, et al. Gut microbiota impact on the peripheral immune response in non-alcoholic fatty liver disease related hepatocellular carcinoma. Nat Commun. 2021;12(1):187. doi:10.1038/s41467-020-20422-7.
   PubMed Web of Science ®Google Scholar
• Ponziani FR, Bhoori S, Castelli C, Putignani L, Rivoltini L, Del Chierico F, Sanguinetti M, Morelli D, Paroni Sterbini F, Petito V, et al. Hepatocellular carcinoma is associated with gut microbiota profile and inflammation in nonalcoholic fatty liver disease. Hepatology. 2019;69(1):107–120. doi:10.1002/hep.30036.
   PubMed Web of Science ®Google Scholar
• Maccioni L, Gao B, Leclercq S, Pirlot B, Horsmans Y, De Timary P, Leclercq I, Fouts D, Schnabl B, Stärkel P, et al. Intestinal permeability, microbial translocation, changes in duodenal and fecal microbiota, and their associations with alcoholic liver disease progression in humans. Gut Microbes. 2020;12(1):1782157. doi:10.1080/19490976.2020.1782157.
   PubMed Web of Science ®Google Scholar
• Guo S, Al-Sadi R, Said HM, Ma TY. Lipopolysaccharide causes an increase in intestinal tight junction permeability in vitro and in vivo by inducing enterocyte membrane expression and localization of TLR-4 and CD14. Am J Pathol. 2013;182(2):375–387. doi:10.1016/j.ajpath.2012.10.014.
   PubMed Web of Science ®Google Scholar
• Dapito Dianne H, Mencin A, Gwak G-Y, Pradere J-P, Jang M-K, Mederacke I, Caviglia J, Khiabanian H, Adeyemi A, Bataller R, et al. Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4. Cancer Cell. 2012;21(4):504–516. doi:10.1016/j.ccr.2012.02.007.
   PubMed Web of Science ®Google Scholar
• Yu LX, Yan HX, Liu Q, Yang W, Wu H-P, Dong W, Tang L, Lin Y, He Y-Q, Zou S-S, et al. Endotoxin accumulation prevents carcinogen‐induced apoptosis and promotes liver tumorigenesis in rodents. Hepatology. 2010;52(4):1322–1333. doi:10.1002/hep.23845.
   PubMed Web of Science ®Google Scholar
• Nighot M, Al-Sadi R, Guo S, Rawat M, Nighot P, Watterson MD, Ma TY. Lipopolysaccharide-induced increase in intestinal epithelial tight permeability is mediated by toll-like receptor 4/myeloid differentiation primary response 88 (MyD88) activation of myosin light chain kinase expression. Am J Pathol. 2017;187(12):2698–2710. doi:10.1016/j.ajpath.2017.08.005.
   PubMed Web of Science ®Google Scholar
• Clayburgh DR, Rosen S, Witkowski ED, Wang F, Blair S, Dudek S, Garcia JGN, Alverdy JC, Turner JR. A differentiation-dependent splice variant of myosin light chain kinase, MLCK1, regulates epithelial tight junction permeability. J Biol Chem. 2004;279(53):55506–55513. doi:10.1074/jbc.M408822200.
   PubMed Web of Science ®Google Scholar
• Liu WT, Jing YY, Gao L, Li R, Yang X, Pan X-R, Yang Y, Meng Y, Hou X-J, Zhao Q-D, et al. Lipopolysaccharide induces the differentiation of hepatic progenitor cells into myofibroblasts constitutes the hepatocarcinogenesis-associated microenvironment. Cell Death Differ. 2020;27(1):85–101. doi:10.1038/s41418-019-0340-7.
   PubMed Web of Science ®Google Scholar
• Li X-Y, Yang X, Zhao Q-D, Han Z-P, Liang L, Pan X-R, Zhu J-N, Li R, Wu M-C, Wei L-X, et al. Lipopolysaccharide promotes tumorigenicity of hepatic progenitor cells by promoting proliferation and blocking normal differentiation. Cancer Lett. 2017;386:35–46. doi:10.1016/j.canlet.2016.10.044.
   PubMed Web of Science ®Google Scholar
• Ma C, Han M, Heinrich B, Fu Q, Zhang Q, Sandhu M, Agdashian D, Terabe M, Berzofsky JA, Fako V, et al. Gut microbiome–mediated bile acid metabolism regulates liver cancer via NKT cells. Science. 2018;360(6391):eaan5931. doi:10.1126/science.aan5931.
   PubMed Web of Science ®Google Scholar
• Singh V, Yeoh BS, Chassaing B, Xiao X, Saha P, Aguilera Olvera R, Lapek JD, Zhang L, Wang W-B, Hao S, et al. Dysregulated microbial fermentation of soluble fiber induces cholestatic liver cancer. Cell. 2018;175(3):679–94.e22. doi:10.1016/j.cell.2018.09.004.
   PubMed Web of Science ®Google Scholar
• Sun M, Wu W, Chen L, Yang W, Huang X, Ma C, Chen F, Xiao Y, Zhao Y, Ma C, et al. Microbiota-derived short-chain fatty acids promote Th1 cell IL-10 production to maintain intestinal homeostasis. Nat Commun. 2018;9(1):3555. doi:10.1038/s41467-018-05901-2.
   PubMed Web of Science ®Google Scholar
• Lasitschka F, Giese T, Paparella M, Kurzhals SR, Wabnitz G, Jacob K, Gras J, Bode KA, Heninger A-K, Sziskzai T, et al. Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n-butyrate. Immun Inflamm Dis. 2017;5(4):480–492. doi:10.1002/iid3.184.
   PubMed Web of Science ®Google Scholar
• Chang PV, Hao L, Offermanns S, Medzhitov R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc Natl Acad Sci USA. 2014;111(6):2247–2252. doi:10.1073/pnas.1322269111.
   PubMed Web of Science ®Google Scholar
• San Yeoh B, Saha P, Golonka RM, Zou J, Petrick JL, Abokor AA, Xiao X, Bovilla VR, Bretin ACA, Rivera-Esteban J, et al. Enterohepatic shunt-driven cholemia predisposes to liver cancer. Gastroenterology. 2022;163(6):1658–1671.e16. doi:10.1053/j.gastro.2022.08.033.
   PubMed Web of Science ®Google Scholar
• Režen T, Rozman D, Kovács T, Kovács P, Sipos A, Bai P, Mikó E. The role of bile acids in carcinogenesis. Cell Mol Life Sci. 2022;79(5):243. doi:10.1007/s00018-022-04278-2.
   PubMed Web of Science ®Google Scholar
• Colosimo S, Tomlinson JW. Bile acids as drivers and biomarkers of hepatocellular carcinoma. World J Hepatol. 2022;14(9):1730–1738. doi:10.4254/wjh.v14.i9.1730.
   PubMed Web of Science ®Google Scholar
• Kong B, Zhu Y, Li G, Williams JA, Buckley K, Tawfik O, Luyendyk JP, Guo GL. Mice with hepatocyte-specific FXR deficiency are resistant to spontaneous but susceptible to cholic acid-induced hepatocarcinogenesis. Am J Physiol Gastrointest Liver Physiol. 2016;310(5):G295–302. doi:10.1152/ajpgi.00134.2015.
   PubMed Web of Science ®Google Scholar
• Li G, Zhu Y, Tawfik O, Kong B, Williams JA, Zhan L, Kassel KM, Luyendyk JP, Wang L, Guo GL, et al. Mechanisms of STAT3 activation in the liver of FXR knockout mice. Am J Physiol Gastrointest Liver Physiol. 2013;305(11):G829–37. doi:10.1152/ajpgi.00155.2013.
   PubMed Web of Science ®Google Scholar
• Shen Y, Lu C, Song Z, Qiao C, Wang J, Chen J, Zhang C, Zeng X, Ma Z, Chen T, et al. Ursodeoxycholic acid reduces antitumor immunosuppression by inducing CHIP-mediated TGF-β degradation. Nat Commun. 2022;13(1):3419. doi:10.1038/s41467-022-31141-6.
   PubMed Web of Science ®Google Scholar
• Sun R, Zhang Z, Bao R, Guo X, Gu Y, Yang W, Wei J, Chen X, Tong L, Meng J, et al. Loss of SIRT5 promotes bile acid-induced immunosuppressive microenvironment and hepatocarcinogenesis. J Hepatol. 2022;77(2):453–466. doi:10.1016/j.jhep.2022.02.030.
   PubMed Web of Science ®Google Scholar
• Nguyen PT, Kanno K, Pham QT, Kikuchi Y, Kakimoto M, Kobayashi T, Otani Y, Kishikawa N, Miyauchi M, Arihiro K, et al. Senescent hepatic stellate cells caused by deoxycholic acid modulates malignant behavior of hepatocellular carcinoma. J Cancer Res Clin Oncol. 2020;146(12):3255–3268. doi:10.1007/s00432-020-03374-9.
   PubMed Web of Science ®Google Scholar
• Grivennikov SI, Greten FR, Karin M. Immunity, Inflammation, and Cancer. Cell. 2010;140(6):883–899. doi:10.1016/j.cell.2010.01.025.
   PubMed Web of Science ®Google Scholar
• Hullar MAJ, Jenkins IC, Randolph TW, Curtis KR, Monroe KR, Ernst T, Shepherd JA, Stram DO, Cheng I, Kristal BS, et al. Associations of the gut microbiome with hepatic adiposity in the multiethnic cohort adiposity phenotype study. Gut Microbes. 2021;13(1):1965463. doi:10.1080/19490976.2021.1965463.
   PubMed Web of Science ®Google Scholar
• Zhang N, Gou Y, Liang S, Chen N, Liu Y, He Q, Zhang J. Dysbiosis of gut microbiota promotes hepatocellular carcinoma progression by regulating the immune response. J Immunol Res. 2021;2021:1–13. doi:10.1155/2021/4973589.
   Web of Science ®Google Scholar
• Kang Y, Cai Y, Yang Y. The gut microbiome and hepatocellular carcinoma: implications for early diagnostic biomarkers and novel therapies. Liver Cancer. 2022;11(2):113–125. doi:10.1159/000521358.
   PubMed Web of Science ®Google Scholar
• Shetty S, Lalor PF, Adams DH. Liver sinusoidal endothelial cells - gatekeepers of hepatic immunity. Nat Rev Gastroenterol Hepatol. 2018;15(9):555–567. doi:10.1038/s41575-018-0020-y.
   PubMed Web of Science ®Google Scholar
• Gola A, Dorrington MG, Speranza E, Sala C, Shih RM, Radtke AJ, Wong HS, Baptista AP, Hernandez JM, Castellani G, et al. Commensal-driven immune zonation of the liver promotes host defence. Nature. 2021;589(7840):131–136. doi:10.1038/s41586-020-2977-2.
   PubMed Web of Science ®Google Scholar
• English K, Bowen DG, Bertolino P. Zone defence - the gut microbiota position macrophages for optimal liver protection. Immunol Cell Biol. 2021;99(6):565–569. doi:10.1111/imcb.12476.
   PubMed Web of Science ®Google Scholar
• Kang T-W, Yevsa T, Woller N, Hoenicke L, Wuestefeld T, Dauch D, Hohmeyer A, Gereke M, Rudalska R, Potapova A, et al. Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Nature. 2011;479(7374):547–551. doi:10.1038/nature10599.
   PubMed Web of Science ®Google Scholar
• Schneider KM, Mohs A, Gui W, Galvez EJC, Candels LS, Hoenicke L, Muthukumarasamy U, Holland CH, Elfers C, Kilic K, et al. Imbalanced gut microbiota fuels hepatocellular carcinoma development by shaping the hepatic inflammatory microenvironment. Nat Commun. 2022;13(1):3964. doi:10.1038/s41467-022-31312-5.
   PubMed Web of Science ®Google Scholar
• Tobin RP, Jordan KR, Kapoor P, Spongberg E, Davis D, Vorwald VM, Couts KL, Gao D, Smith DE, Borgers JSW, et al. IL-6 and IL-8 are linked with myeloid-derived suppressor cell accumulation and correlate with poor clinical outcomes in melanoma patients. Front Oncol. 2019;9:1223. doi:10.3389/fonc.2019.01223.
   PubMed Web of Science ®Google Scholar
• Arpaia N, Campbell C, Fan X, Dikiy S, van der Veeken J, deRoos P, Liu H, Cross JR, Pfeffer K, Coffer PJ, et al. Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation. Nature. 2013;504(7480):451–455. doi:10.1038/nature12726.
   PubMed Web of Science ®Google Scholar
• Liu J, Tan Y, Cheng H, Zhang D, Feng W, Peng C. Functions of gut microbiota metabolites, current status and future perspectives. Aging Dis. 2022;13(4):1106–1126. doi:10.14336/AD.2022.0104.
   PubMed Web of Science ®Google Scholar
• Visekruna A, Luu M. The role of short-chain fatty acids and bile acids in intestinal and liver function, inflammation, and carcinogenesis. Front Cell Dev Biol. 2021;9. doi:10.3389/fcell.2021.703218.
   PubMed Web of Science ®Google Scholar
• Ren Z, Li A, Jiang J, Zhou L, Yu Z, Lu H, Xie H, Chen X, Shao L, Zhang R, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut. 2019;68(6):1014–1023. doi:10.1136/gutjnl-2017-315084.
   PubMed Web of Science ®Google Scholar
• Lapidot Y, Amir A, Nosenko R, Uzan-Yulzari A, Veitsman E, Cohen-Ezra O, Davidov Y, Weiss P, Bradichevski T, Segev S, et al. Alterations in the gut microbiome in the progression of cirrhosis to hepatocellular carcinoma. mSystems. 2020;5(3):e00153–20. doi:10.1128/mSystems.00153-20.
   PubMed Web of Science ®Google Scholar
• Luu M, Riester Z, Baldrich A, Reichardt N, Yuille S, Busetti A, Klein M, Wempe A, Leister H, Raifer H, et al. Microbial short-chain fatty acids modulate CD8+ T cell responses and improve adoptive immunotherapy for cancer. Nat Commun. 2021;12(1):4077. doi:10.1038/s41467-021-24331-1.
   PubMed Web of Science ®Google Scholar
• Singh V, Yeoh BS, Abokor AA, Golonka RM, Tian Y, Patterson AD, Joe B, Heikenwalder M, Vijay-Kumar M. Vancomycin prevents fermentable fiber-induced liver cancer in mice with dysbiotic gut microbiota. Gut Microbes. 2020;11(4):1077–1091. doi:10.1080/19490976.2020.1743492.
   PubMed Web of Science ®Google Scholar
• Zekry A, El-Omar EM. A tale of two fibers: A liver twist! Gastroenterology. 2022;163(6):1495–1497. doi:10.1053/j.gastro.2022.09.012.
   PubMed Web of Science ®Google Scholar
• Sydor S, Best J, Messerschmidt I, Manka P, Vilchez-Vargas R, Brodesser S, Lucas C, Wegehaupt A, Wenning C, Aßmuth S, et al. Altered microbiota diversity and bile acid signaling in cirrhotic and noncirrhotic NASH-HCC. Clin Transl Gastroenterol. 2020;11(3):e00131. doi:10.14309/ctg.0000000000000131.
   PubMedGoogle Scholar
• Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, et al. Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature. 2013;499(7456):97–101. doi:10.1038/nature12347.
   PubMed Web of Science ®Google Scholar
• Larabi AB, Masson HLP, Bäumler AJ. Bile acids as modulators of gut microbiota composition and function. Gut Microbes. 2023;15(1):2172671. doi:10.1080/19490976.2023.2172671.
   PubMed Web of Science ®Google Scholar
• Attia Y, Tawfiq R, Adel A, Elmazar M. The FXR agonist, obeticholic acid, suppresses HCC proliferation & metastasis: Role of IL-6/STAT3 signalling pathway. Sci Rep. 2017;7(1). doi:10.1038/s41598-017-12629-4.
   Google Scholar
• Paik D, Yao L, Zhang Y, Bae S, D’Agostino GD, Zhang M, Kim E, Franzosa EA, Avila-Pacheco J, Bisanz JE, et al. Human gut bacteria produce ΤΗ17-modulating bile acid metabolites. Nature. 2022;603(7903):907–912. doi:10.1038/s41586-022-04480-z.
   PubMed Web of Science ®Google Scholar
• Lan YT, Fan XP, Fan YC, Zhao J, Wang K. Change in the Treg/Th17 cell imbalance in hepatocellular carcinoma patients and its clinical value. Med. 2017;96(32):e7704. doi:10.1097/MD.0000000000007704.
   PubMed Web of Science ®Google Scholar
• Lee P-C, Wu C-J, Hung Y-W, Lee CJ, Chi C-T, Lee I-C, Yu-Lun K, Chou S-H, Luo J-C, Hou M-C, et al. Gut microbiota and metabolites associate with outcomes of immune checkpoint inhibitor–treated unresectable hepatocellular carcinoma. J Immunother Cancer. 2022;10(6):e004779. doi:10.1136/jitc-2022-004779.
   PubMed Web of Science ®Google Scholar
• Smith PM, Howitt MR, Panikov N, Michaud M, Gallini CA, Bohlooly-Y M, Glickman JN, Garrett WS. The microbial metabolites, short-chain fatty acids, regulate colonic treg cell homeostasis. Science. 2013;341(6145):569–573. doi:10.1126/science.1241165.
   PubMed Web of Science ®Google Scholar
• Pinato DJ, Li X, Mishra-Kalyani P, D’Alessio A, Fulgenzi CAM, Scheiner B, Pinter M, Wei G, Schneider J, Rivera DR, et al. Association between antibiotics and adverse oncological outcomes in patients receiving targeted or immune-based therapy for hepatocellular carcinoma. JHEP Rep. 2023;5(6):100747. doi:10.1016/j.jhepr.2023.100747.
   PubMedGoogle Scholar
• Cheung KS, Ka LL, Leung WK. Antibiotics associated with lower survival in hepatocellular cancer patients receiving immune checkpoint inhibitors independent of tumor status. Liver Cancer. 2023;12(1):91–92. doi:10.1159/000528824.
   PubMed Web of Science ®Google Scholar
• Anania C, Perla FM, Olivero F, Pacifico L, Chiesa C. Mediterranean diet and nonalcoholic fatty liver disease. World J Gastroenterol. 2018;24(19):2083–2094. doi:10.3748/wjg.v24.i19.2083.
   PubMed Web of Science ®Google Scholar
• Gelli C, Tarocchi M, Abenavoli L, Di Renzo L, Galli A, De Lorenzo A. Effect of a counseling-supported treatment with the Mediterranean diet and physical activity on the severity of the non-alcoholic fatty liver disease. World J Gastroenterol. 2017;23(17):3150–3162. doi:10.3748/wjg.v23.i17.3150.
   PubMed Web of Science ®Google Scholar
• Baratta F, Pastori D, Polimeni L, Bucci T, Ceci F, Calabrese C, Ernesti I, Pannitteri G, Violi F, Angelico F, et al. Adherence to Mediterranean diet and non-alcoholic fatty liver disease: effect on insulin resistance. Am J Gastroenterol. 2017;112(12):1832–1839. doi:10.1038/ajg.2017.371.
   PubMed Web of Science ®Google Scholar
• Ryan MC, Itsiopoulos C, Thodis T, Ward G, Trost N, Hofferberth S, O’Dea K, Desmond PV, Johnson NA, Wilson AM, et al. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013;59(1):138–143. doi:10.1016/j.jhep.2013.02.012.
   PubMed Web of Science ®Google Scholar
• Trovato FM, Martines GF, Brischetto D, Trovato G, Catalano D. Neglected features of lifestyle: Their relevance in non-alcoholic fatty liver disease. World J Hepatol. 2016;8(33):1459–1465. doi:10.4254/wjh.v8.i33.1459.
   PubMedGoogle Scholar
• Bajaj JS, Idilman R, Mabudian L, Hood M, Fagan A, Turan D, White MB, Karakaya F, Wang J, Atalay R, et al. Diet affects gut microbiota and modulates hospitalization risk differentially in an international cirrhosis cohort. Hepatology. 2018;68(1):234–247. doi:10.1002/hep.29791.
   PubMed Web of Science ®Google Scholar
• De Filippis F, Pellegrini N, Vannini L, Jeffery IB, La Storia A, Laghi L, Serrazanetti DI, Di Cagno R, Ferrocino I, Lazzi C, et al. High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome. Gut. 2016;65(11):1812–1821. doi:10.1136/gutjnl-2015-309957.
   PubMed Web of Science ®Google Scholar
• Merra G, Noce A, Marrone G, Cintoni M, Tarsitano MG, Capacci A, De Lorenzo A. Influence of Mediterranean diet on human gut microbiota. Nutrients. 2020;13(1):7. doi:10.3390/nu13010007.
   PubMed Web of Science ®Google Scholar
• Godny L, Reshef L, Sharar Fischler T, Elial-Fatal S, Pfeffer-Gik T, Raykhel B, Rabinowitz K, Levi-Barda A, Perets TT, Barkan R, et al. Increasing adherence to the Mediterranean diet and lifestyle is associated with reduced fecal calprotectin and intra-individual changes in microbial composition of healthy subjects. Gut Microbes. 2022;14(1):2120749. doi:10.1080/19490976.2022.2120749.
   PubMed Web of Science ®Google Scholar
• Pastori D, Carnevale R, Nocella C, Novo M, Santulli M, Cammisotto V, Menichelli D, Pignatelli P, Violi F. Gut-derived serum lipopolysaccharide is associated with enhanced risk of major adverse cardiovascular events in atrial fibrillation: effect of adherence to Mediterranean diet. J Am Heart Assoc. 2017;6(6). doi:10.1161/JAHA.117.005784.
   PubMed Web of Science ®Google Scholar
• André P, Pais de Barros J-P, Mj Merle B, Samieri C, Helmer C, Delcourt C, Féart C. Mediterranean diet and prudent diet are both associated with low circulating esterified 3-hydroxy fatty acids, a proxy of LPS burden, among older adults. Am J Clin Nutr. 2021;114(3):1080–1091. doi:10.1093/ajcn/nqab126.
   PubMed Web of Science ®Google Scholar
• Duarte-Salles T, Fedirko V, Stepien M, Aleksandrova K, Bamia C, Lagiou P, Laursen ASD, Hansen L, Overvad K, Tjønneland A, et al. Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort. Int J Cancer. 2015;137(11):2715–2728. doi:10.1002/ijc.29643.
   PubMed Web of Science ®Google Scholar
• George ES, Sood S, Broughton A, Cogan G, Hickey M, Chan WS, Sudan S, Nicoll AJ. The association between diet and hepatocellular carcinoma: A systematic review. Nutrients. 2021;13(1):172. doi:10.3390/nu13010172.
   PubMed Web of Science ®Google Scholar
• Moussa I, Day RS, Li R, Kaseb A, Jalal PK, Daniel‐MacDougall C, Hatia RI, Abdelhakeem A, Rashid A, Chun YS, et al. Association of dietary fat intake and hepatocellular carcinoma among US adults. Cancer Med. 2021;10(20):7308–7319. doi:10.1002/cam4.4256.
   PubMed Web of Science ®Google Scholar
• Polesel J, Talamini R, Montella M, Maso LD, Crovatto M, Parpinel M, Izzo F, Tommasi LG, Serraino D, Vecchia CL, et al. Nutrients intake and the risk of hepatocellular carcinoma in Italy. Eur J Cancer. 2007;43(16):2381–2387. doi:10.1016/j.ejca.2007.07.012.
   PubMed Web of Science ®Google Scholar
• López-Salazar V, Tapia MS, Tobón-Cornejo S, Díaz D, Alemán-Escondrillas G, Granados-Portillo O, Noriega L, Tovar AR, Torres N. Consumption of soybean or olive oil at recommended concentrations increased the intestinal microbiota diversity and insulin sensitivity and prevented fatty liver compared to the effects of coconut oil. J Nutr Biochem. 2021;94:108751. doi:10.1016/j.jnutbio.2021.108751.
   PubMed Web of Science ®Google Scholar
• Lyons CL, Finucane OF, Murphy AM, Cooke AA, Viollet B, Vieira PM, Oldham W, Kahn BB, Roche HM. Monounsaturated fatty acids impede inflammation partially through activation of AMPK. FASEB J. 2016;30(S1):296–5.
   Google Scholar
• Rocha DM, Bressan J, Hermsdorff HH. The role of dietary fatty acid intake in inflammatory gene expression: a critical review. Sao Paulo Med J. 2017;135(2):157–168. doi:10.1590/1516-3180.2016.008607072016.
   PubMed Web of Science ®Google Scholar
• Shen W, Gaskins HR, McIntosh MK. Influence of dietary fat on intestinal microbes, inflammation, barrier function and metabolic outcomes. J Nutr Biochem. 2014;25(3):270–280. doi:10.1016/j.jnutbio.2013.09.009.
   PubMed Web of Science ®Google Scholar
• Liu F, Smith AD, Solano-Aguilar G, Wang TTY, Pham Q, Beshah E, Tang Q, Urban JF, Xue C, Li RW, et al. Mechanistic insights into the attenuation of intestinal inflammation and modulation of the gut microbiome by krill oil using in vitro and in vivo models. Microbiome. 2020;8(1):83. doi:10.1186/s40168-020-00843-8.
   PubMed Web of Science ®Google Scholar
• Fu Y, Wang Y, Gao H, Li D, Jiang R, Ge L, Tong C, Xu K. Associations among dietary omega-3 polyunsaturated fatty acids, the gut microbiota, and intestinal immunity. Mediators Inflamm. 2021;2021:1–11. doi:10.1155/2021/8879227.
   Web of Science ®Google Scholar
• Rong Y, Dong Z, Hong Z, Jin Y, Zhang W, Zhang B, Mao W, Kong H, Wang C, Yang B, et al. Reactivity toward Bifidobacterium longum and Enterococcus hirae demonstrate robust CD8(+) T cell response and better prognosis in HBV-related hepatocellular carcinoma. Exp Cell Res. 2017;358(2):352–359. doi:10.1016/j.yexcr.2017.07.009.
   PubMed Web of Science ®Google Scholar
• Bajaj JS, Ng SC, Schnabl B. Promises of microbiome-based therapies. J Hepatol. 2022;76(6):1379–1391. doi:10.1016/j.jhep.2021.12.003.
   PubMed Web of Science ®Google Scholar
• Zhou D, Pan Q, Shen F, Cao H-X, Ding W-J, Chen Y-W, Fan J-G. Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci Rep. 2017;7(1):1529. doi:10.1038/s41598-017-01751-y.
   PubMed Web of Science ®Google Scholar
• Davar D, Dzutsev AK, McCulloch JA, Rodrigues RR, Chauvin J-M, Morrison RM, Deblasio RN, Menna C, Ding Q, Pagliano O, et al. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science. 2021;371(6529):595–602. doi:10.1126/science.abf3363.
   PubMed Web of Science ®Google Scholar
• Baruch EN, Youngster I, Ben-Betzalel G, Ortenberg R, Lahat A, Katz L, Adler K, Dick-Necula D, Raskin S, Bloch N, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science. 2021;371(6529):602–609. doi:10.1126/science.abb5920.
   PubMed Web of Science ®Google Scholar
• Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, Fluckiger A, Messaoudene M, Rauber C, Roberti MP, et al. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Science. 2018;359(6371):91–97. doi:10.1126/science.aan3706.
   PubMed Web of Science ®Google Scholar
• Kaźmierczak-Siedlecka K, Skonieczna-Żydecka K, Hupp T, Duchnowska R, Marek-Trzonkowska N, Połom K. Next-generation probiotics – do they open new therapeutic strategies for cancer patients? Gut Microbes. 2022;14(1):2035659. doi:10.1080/19490976.2022.2035659.
   PubMed Web of Science ®Google Scholar
• Lee NY, Yoon SJ, Han DH, Gupta H, Youn GS, Shin MJ, Ham YL, Kwak MJ, Kim BY, Yu JS, et al. Lactobacillus and pediococcus ameliorate progression of non-alcoholic fatty liver disease through modulation of the gut microbiome. Gut Microbes. 2020;11(4):882–899. doi:10.1080/19490976.2020.1712984.
   PubMed Web of Science ®Google Scholar
• Li J, Sung CYJ, Lee N, Ni Y, Pihlajamäki J, Panagiotou G, El-Nezami H. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice. Proc Natl Acad Sci USA. 2016;113(9):E1306–E15. doi:10.1073/pnas.1518189113.
   PubMed Web of Science ®Google Scholar
• Zhang H-L, Yu L-X, Yang W, Tang L, Lin Y, Wu H, Zhai B, Tan Y-X, Shan L, Liu Q, et al. Profound impact of gut homeostasis on chemically-induced pro-tumorigenic inflammation and hepatocarcinogenesis in rats. J Hepatol. 2012;57(4):803–812. doi:10.1016/j.jhep.2012.06.011.
   PubMed Web of Science ®Google Scholar
• El-Nezami HS, Polychronaki NN, Ma J, Zhu H, Ling W, Salminen EK, Juvonen RO, Salminen SJ, Poussa T, Mykkänen HM, et al. Probiotic supplementation reduces a biomarker for increased risk of liver cancer in young men from Southern China. Am J Clin Nutr. 2006;83(5):1199–1203. doi:10.1093/ajcn/83.5.1199.
   PubMed Web of Science ®Google Scholar
• El-Nezami H, Mykkänen H, Kankaanpää P, Salminen S, Ahokas J. Ability of Lactobacillus and Propionibacterium strains to remove aflatoxin B1 from the chicken duodenum. J Food Prot. 2000;63(4):549–552. doi:10.4315/0362-028X-63.4.549.
   PubMed Web of Science ®Google Scholar
• Gutiérrez-Díaz I, Fernández-Navarro T, Sánchez B, Margolles A, González S. Mediterranean diet and faecal microbiota: a transversal study. Food Funct. 2016;7(5):2347–2356. doi:10.1039/C6FO00105J.
   PubMed Web of Science ®Google Scholar
• Philips CA, Pande A, Shasthry SM, Jamwal KD, Khillan V, Chandel SS, Kumar G, Sharma MK, Maiwall R, Jindal A, et al. Healthy donor fecal microbiota transplantation in steroid-ineligible severe alcoholic hepatitis: A pilot study. Clin Gastroenterol Hepatol. 2017;15(4):600–602. doi:10.1016/j.cgh.2016.10.029.
   PubMed Web of Science ®Google Scholar
• Spahn S, Roessler D, Pompilia R, Gabernet G, Gladstone BP, Horger M, Biskup S, Feldhahn M, Nahnsen S, Hilke FJ, et al. Clinical and genetic tumor characteristics of responding and non-responding patients to PD-1 inhibition in hepatocellular carcinoma. Cancers Basel. 2020;12(12):3830. doi:10.3390/cancers12123830.
   PubMed Web of Science ®Google Scholar
• Zheng Y, Wang T, Tu X, Huang Y, Zhang H, Tan D, Jiang W, Cai S, Zhao P, Song R, et al. Gut microbiome affects the response to anti-PD-1 immunotherapy in patients with hepatocellular carcinoma. J Immunother Cancer. 2019;7(1):193. doi:10.1186/s40425-019-0650-9.
   PubMed Web of Science ®Google Scholar
• Yeh F-S, Yu MC, Mo C-C, Luo S, Tong MJ, Henderson BE. Hepatitis B virus, aflatoxins, and hepatocellular carcinoma in southern Guangxi, China. Cancer Res. 1989;49:2506–2509.
   PubMed Web of Science ®Google Scholar