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 Cancer J Clin. 2021;71(3):209–49. https://doi.org/10.3322/caac.21660.

Article  PubMed  Google Scholar 

Ghiringhelli F, Apetoh L. Enhancing the anticancer effects of 5-fluorouracil: current challenges and future perspectives. Biomed J. 2015;38(2):111–6. https://doi.org/10.4103/2319-4170.130923.

Article  PubMed  Google Scholar 

Longley DB, Harkin DP, Johnston PG. 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003;3(5):330–8. https://doi.org/10.1038/nrc1074.

CAS  Article  PubMed  Google Scholar 

Hamouda N, Sano T, Oikawa Y, Ozaki T, Shimakawa M, Matsumoto K, Amagase K, Higuchi K, Kato S. Apoptosis, dysbiosis and expression of inflammatory cytokines are sequential events in the development of 5-fluorouracil-induced intestinal muco-sitis in mice. Basic Clin Pharmacol Toxicol. 2017;121(3):159–68. https://doi.org/10.1111/bcpt.12793.

CAS  Article  PubMed  Google Scholar 

Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100(S9):1995–2025. https://doi.org/10.1002/cncr.20162.

Article  PubMed  Google Scholar 

Neish AS. Microbes in gastrointestinal health and disease. Gastroenterology. 2009;136(1):65–80. https://doi.org/10.1053/j.gastro.2008.10.080.

Article  PubMed  Google Scholar 

Nicholson JK, Holmes E, Wilson ID. Gut microorganisms, mammalian metabolism and personalized health care. Nat Rev Microbiol. 2005;3(5):431–8. https://doi.org/10.1038/nrmicro1152.

CAS  Article  PubMed  Google Scholar 

Alexander JL, Wilson ID, Teare J, Marchesi JR, Nicholson JK, Kinross JM. Gut mi-crobiota modulation of chemotherapy efficacy and toxicity. Nat Rev Gastroenterol Hepatol. 2017;14(6):356–65. https://doi.org/10.1038/nrgastro.2017.20.

CAS  Article  PubMed  Google Scholar 

Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillère R, Hannani D, Enot DP, Pfirschke C, Engblom C, Pittet MJ. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342(6161):971–6. https://doi.org/10.1126/science.1240537.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Iida N, Dzutsev A, Stewart CA, Smith L, Bouladoux N, Weingarten RA, Molina DA, Salcedo R, Back T, Cramer S. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science. 2013;342(6161):967–70. https://doi.org/10.1126/science.1240527.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Vétizou M, Pitt JM, Daillère R, Lepage P, Waldschmitt N, Flament C, Rusakiewicz S, Routy B, Roberti MP, Duong CP. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079–84. https://doi.org/10.1126/science.aad1329.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Man Lei Y, Jabri B, Alegre M-L. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science. 2015;350(6264):1084–9. https://doi.org/10.1126/science.aac4255.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Wong SH, Yu J. Gut microbiota in colorectal cancer: mechanisms of action and cl-inical applications. Nat Rev Gastroenterol Hepatol. 2019;16(11):690–704. https://doi.org/10.1038/s41575-019-0209-8.

CAS  Article  PubMed  Google Scholar 

Brennan CA, Garrett WS. Gut microbiota, inflammation, and colorectal cancer. Annu Rev Microbiol. 2016;70:395–411. https://doi.org/10.1146/annurev-micro-102215-095513.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Wu J, Gan Y, Li M, Chen L, Liang J, Zhuo J, Luo H, Xu N, Wu X, Wu Q. Patcho-uli alcohol attenuates 5-fluorouracil-induced intestinal mucositis via TLR2/MyD88/NF-kB pathway and regulation of microbiota. Biomed Pharmacother. 2020;124: 109883. https://doi.org/10.1016/j.biopha.2020.109883.

CAS  Article  PubMed  Google Scholar 

Li H-L, Lu L, Wang X-S, Qin L-Y, Wang P, Qiu S-P, Wu H, Huang F, Zhang B-B, Shi H-L. Alteration of gut microbiota and inflammatory cytokine/chemokine profil-es in 5-fluorouracil induced intestinal mucositis. Front Cell Infect Microbiol. 2017;7:455. https://doi.org/10.3389/fcimb.2017.00455.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Yuan L, Zhang S, Li H, Yang F, Mushtaq N, Ullah S, Shi Y, An C, Xu J. The influence of gut microbiota dysbiosis to the efficacy of 5-Fluorouracil treatment on colorectal cancer. Biomed Pharmacother. 2018;108:184–93. https://doi.org/10.1016/j.biopha.2018.08.165.

CAS  Article  PubMed  Google Scholar 

Sougiannis A, VanderVeen B, Enos R, Velazquez K, Bader J, Carson M, Chatzist-amou I, Walla M, Pena M, Kubinak J. Impact of 5 fluorouracil chemotherapy on gut inflammation, functional parameters, and gut microbiota. Brain, behavior, and im-munity. 2019;80:44–55. https://doi.org/10.1016/j.bbi.2019.02.020.

CAS  Article  Google Scholar 

Justino PF, Melo LF, Nogueira AF, Costa JV, Silva LM, Santos CM, Mendes WO, Costa MR, Franco AX, Lima AA. Treatment with Saccharomyces boulardii reduces the inflammation and dysfunction of the gastrointestinal tract in 5-fluorouracil-induced intestinal mucositis in mice. Br J Nutr. 2014;111(9):1611–21. https://doi.org/10.1017/S0007114513004248.

CAS  Article  PubMed  Google Scholar 

Wu T, Munro AJ, Guanjian L, Liu GJ. Chinese medical herbs for chemotherapy side effects in colorectal cancer patients. Cochrane Database Syst Rev. 2005. https://doi.org/10.1002/14651858.CD004540.pub2.

Article  PubMed  PubMed Central  Google Scholar 

Chen K-J, Huang Y-L, Kuo L-M, Chen Y-T, Hung C-F, Hsieh P-W. Protective role of casuarinin from Melastoma malabathricum against a mouse model of 5-fluorouracil–induced intestinal mucositis: Impact on inflammation and gut microbiota dys-biosis. Phytomedicine. 2022;101: 154092. https://doi.org/10.1016/j.phymed.2022.154092.

CAS  Article  PubMed  Google Scholar 

Huang G, Khan I, Li X, Chen L, Leong W, Ho LT, Hsiao WLW. Ginsenosides Rb3 and Rd reduce polyps formation while reinstate the dysbiotic gut microbiota and the intestinal microenvironment in ApcMin/+ mice. Sci Rep. 2017;7(1):12552. https://doi.org/10.1038/s41598-017-12644-5.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Khan I, Huang G, Li X, Leong W, Xia W, Hsiao WLW. Mushroom polysaccharides from Ganoderma lucidum and Poria cocos reveal prebiotic functions. J Funct Foods. 2018;41:191–201. https://doi.org/10.1016/j.jff.2017.12.046.

CAS  Article  Google Scholar 

Khan I, Huang G, Li X, Liao W, Leong WK, Xia W, Bian X, Wu J, Hsiao WLW. Mushroom polysaccharides and jiaogulan saponins exert cancer preventive effects by shaping the gut microbiota and microenvironment in ApcMin/+ mice. Pharmacolo-gical Res. 2019;148: 104448. https://doi.org/10.1016/j.phrs.2019.104448.

CAS  Article  Google Scholar 

Xia W, Li X, Khan I, Yin L, Su L, Leong WK, Bian X, Su J, Hsiao W, Huang G. Lycium Berry polysaccharides strengthen gut microenvironment and modulate gut microbiota of the mice. Evid Based Complement Alternat Med. 2020. https://doi.org/10.1155/2020/8097021.

Article  PubMed  PubMed Central  Google Scholar 

Sun S-S, Wang K, Ma K, Bao L, Liu H-W. An insoluble polysaccharide from the sclerotium of Poria cocos improves hyperglycemia, hyperlipidemia and hepatic steatosis in ob/ob mice via modulation of gut microbiota. Chin J Nat Med. 2019;17(1):3–14. https://doi.org/10.1016/s1875-5364(19)30003-2.

CAS  Article  PubMed  Google Scholar 

Jiang Y, Fan L. The effect of Poria cocos ethanol extract on the intestinal barrier function and intestinal microbiota in mice with breast cancer. J Ethnopharmacol. 2021;266: 113456. https://doi.org/10.1016/j.jep.2020.113456.

CAS  Article  PubMed  Google Scholar 

Wang N, Liu D, Guo J, Sun Y, Guo T, Zhu X. Molecular mechanism of Poria cocos combined with oxaliplatin on the inhibition of epithelial-mesenchymal transition in gastric cancer cells. Biomed Pharmacother. 2018;102:865–73. https://doi.org/10.1016/j.biopha.2018.03.134.

CAS  Article  PubMed  Google Scholar 

Wang J, Zheng D, Huang F, Zhao A, Kuang J, Ren Z, Chen T, Lei J, Lin J, Wang X, Jia W, Xie G, Zheng X. Theabrownin and Poria cocos polysaccharide improve lipid metabolism via modulation of bile acid and fatty acid metabolism. Front Pharmacol. 2022;13: 875549. https://doi.org/10.3389/fphar.2022.875549.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Lai Y, Yu H, Deng H, Fang Q, Lei H, Liu L, Wu N, Guo X, Song C. Three main metabolites from Wolfiporia cocos (F. A. Wolf) Ryvarden & Gilb regulate the gut microbiota in mice: a comparative study using microbiome-metabolomics. Front Pharmacol. 2022. https://doi.org/10.3389/fphar.2022.911140.

Article  PubMed  PubMed Central  Google Scholar 

Sun S, Wang K, Sun L, Cheng B, Qiao S, Dai H, Shi W, Ma J, Liu H. Therapeutic manipulation of gut microbiota by polysaccharides of Wolfiporia cocos reveals the contribution of the gut fungi-induced PGE2 to alcoholic hepatic steatosis. Gut Microbes. 2020;12(1):1830693. https://doi.org/10.1080/19490976.2020.1830693.

CAS  Article  PubMed  PubMed Central  Google Scholar 

Chen L, Brar MS, Leung FC, Hsiao WW. Triterpenoid herbal saponins enhance beneficial bacteria, decrease sulfate-reducing bacteria, modulate inflammatory intestinal microenvironment and exert cancer preventive effects in ApcMin/+ mice. Oncotarget. 2016;7(21):31226. https://doi.org/10.1080/19490976.2020.

Article  PubMed  PubMed Central  Google Scholar 

Dowd SE, Sun Y, Wolcott RD, Domingo A, Carroll JA. Bacterial tag–encoded FLX amplicon pyrosequencing (bTEFAP) for microbiome studies: bacterial diversity in the ileum of newly weaned Salmonella-infected pigs. Foodborne Pathog Dis. 2008;5(4):459–72. https://doi.org/10.1089/fpd.2008.0107.

CAS