Intestinal flora affects occurrence of hepatocellular carcinoma by regulating tumor microenvironment_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHENG Yan ¹ , XU Lingcong ¹ , ZHOU Yongqiang ¹ , YAN Jiexi ² ,  LI Xun ^1,2,3

1. The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China;
2. Precision Medicine Center, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;
3. Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou 730000, P. R. China;

Corresponding author：

LI Xun, Email: lxdr21@126.com

Keywords：

hepatocellular carcinoma; intestinal flora; tumor microenvironment

DOI：

10.7507/1007-9424.202311036

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To review the role of intestinal flora on the tumor microenvironment and the effect of both on the development of hepatocellular carcinoma (HCC), with a view to providing new ideas on the causes of HCC development and progression. Method Relevant articles in the direction of intestinal flora and tumor microenvironment and HCC as well as the relationship between intestinal flora and tumor microenvironment in recent years were searched and summarized. Results The tumor microenvironment played an important role in the occurrence, development and postoperative recurrence of HCC. The intestinal flora, as one of the important regulators of tumor microenvironment, could induce HCC by affecting the tumor microenvironment in addition to interacting with the liver through the gut-liver axis. Conclusion Intestinal flora can influence to HCC by regulating the tumor microenvironment, and its specific mechanism of action still needs to be further investigated, which can be a new direction for HCC research.

Citation： ZHENG Yan, XU Lingcong, ZHOU Yongqiang, YAN Jiexi, LI Xun. Intestinal flora affects occurrence of hepatocellular carcinoma by regulating tumor microenvironment. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2024, 31(4): 502-507. doi: 10.7507/1007-9424.202311036 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	Kuo CL, Chou HY, Chiu YC, et al. Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. Cancer Lett, 2020, 474: 138-150.
3.	Li W, Wang H, Ma Z, et al. Multi-omics analysis of microen-vironment characteristics and immune escape mechanisms of hepatocellular carcinoma. Front Oncol, 2019, 9: 1019. doi: 10.3389/fonc.2019.01019.
4.	Martínez-Reyes I, Chandel NS. Cancer metabolism: looking forward. Nat Rev Cancer, 2021, 21(10): 669-680.
5.	Yang X, Guo Y, Chen C, et al. Interaction between intestinal microbiota and tumour immunity in the tumour microen-vironment. Immunology, 2021, 164(3): 476-493.
6.	Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther, 2021, 221: 107753. doi: 10.1016/j.pharmthera.2020.107753.
7.	Nejman D, Livyatan I, Fuks G, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science, 2020, 368(6494): 973-980.
8.	Qiu Q, Lin Y, Ma Y, et al. Exploring the emerging role of the gut microbiota and tumor microenvironment in cancer immunotherapy. Front Immunol, 2021, 11: 612202. doi: 10.3389/fimmu.2020.612202.
9.	Chen C, Wang Z, Ding Y, et al. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol, 2023, 14: 1133308. doi: 10.3389/fimmu.2023.1133308.
10.	Doroshow DB, Bhalla S, Beasley MB, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol, 2021, 18(6): 345-362.
11.	Tang T, Huang X, Zhang G, et al. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduct Target Ther, 2021, 6(1): 72. doi: 10.1038/s41392-020-00449-4.
12.	Narunsky-Haziza L, Sepich-Poore GD, Livyatan I, et al. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. Cell, 2022, 185(20): 3789-3806.
13.	Neuzillet C, Marchais M, Vacher S, et al. Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients. Sci Rep, 2021, 11(1): 7870. doi: 10.1038/s41598-021-86816-9.
14.	Kohi S, Macgregor-Das A, Dbouk M, et al. Alterations in the duodenal fluid microbiome of patients with pancreatic cancer. Clin Gastroenterol Hepatol, 2022, 20(2): e196-e227. doi: 10.1016/j.cgh.2020.11.006.
15.	Xie Y, Xie F, Zhou X, et al. Microbiota in tumors: from understanding to application. Adv Sci (Weinh), 2022, 9(21): e2200470. doi: 10.1002/advs.202200470.
16.	Bertocchi A, Carloni S, Ravenda PS, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell, 2021, 39(5): 708-724.
17.	Chen Y, Liu B, Wei Y, et al. Influence of gut and intratumoral microbiota on the immune microenvironment and anti-cancer therapy. Pharmacol Res, 2021, 174: 105966. doi: 10.1016/j.phrs.2021.105966.
18.	Fu A, Yao B, Dong T, et al. Emerging roles of intratumor microbiota in cancer metastasis. Trends Cell Biol, 2023, 33(7): 583-593.
19.	Sas Z, Cendrowicz E, Weinhäuser I, et al. Tumor microenvironment of hepatocellular carcinoma: challenges and opportunities for new treatment options. Int J Mol Sci, 2022, 23(7): 3778. doi: 10.3390/ijms23073778.
20.	Yang Q, Guo N, Zhou Y, et al. The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. Acta Pharm Sin B, 2020, 10(11): 2156-2170.
21.	Pavlović N, Calitz C, Thanapirom K, et al. Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma. Elife, 2020, 9: e55865. doi: 10.7554/eLife.55865.
22.	Yuen VW, Wong CC. Hypoxia-inducible factors and innate immunity in liver cancer. J Clin Invest, 2020, 130(10): 5052-5062.
23.	Kudo M. Scientific rationale for combined immunotherapy with PD-1/PD-L1 antibodies and VEGF inhibitors in advanced hepatocellular carcinoma. Cancers (Basel), 2020, 12(5): 1089. doi: 10.3390/cancers12051089.
24.	Wu Z, Li S, Zhu X. The mechanism of stimulating and mobilizing the immune system enhancing the anti-tumor immunity. Front Immunol, 2021, 12: 682435. doi: 10.3389/fimmu.2021.682435.
25.	El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007, 132(7): 2557-2576.
26.	Boedtkjer E, Pedersen SF. The acidic tumor microenvironment as a driver of cancer. Annu Rev Physiol, 2020, 82: 103-126.
27.	Gao X, Huang H, Wang Y, et al. Tumor immune microen-vironment characterization in hepatocellular carcinoma identifies four prognostic and immunotherapeutically relevant subclasses. Front Oncol, 2021, 10: 610513. doi: 10.3389/fonc.2020.610513.
28.	Huang Y, Fan XG, Wang ZM, et al. Identification of helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol, 2004, 57(12): 1273-1277.
29.	Qu D, Wang Y, Xia Q, et al. Intratumoral microbiome of human primary liver cancer. Hepatol Commun, 2022, 6(7): 1741-1752.
30.	Liu B, Zhou Z, Jin Y, et al. Hepatic stellate cell activation and senescence induced by intrahepatic microbiota disturbances drive progression of liver cirrhosis toward hepatocellular carcinoma. J Immunother Cancer, 2022, 10(1): e003069. doi: 10.1136/jitc-2021-003069.
31.	Poore GD, Kopylova E, Zhu Q, et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature, 2020, 579(7800): 567-574.
32.	Xue C, Chu Q, Zheng Q, et al. Current understanding of the intratumoral microbiome in various tumors. Cell Rep Med, 2023, 4(1): 100884. doi: 10.1016/j.xcrm.2022.100884.
33.	Zhang YJ, Li S, Gan RY, et al. Impacts of gut bacteria on human health and diseases. Int J Mol Sci, 2015, 16(4): 7493-7519.
34.	Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol, 2021, 19(1): 55-71.
35.	Ding RX, Goh WR, Wu RN, et al. Revisit gut microbiota and its impact on human health and disease. J Food Drug Anal, 2019, 27(3): 623-631.
36.	Kuziel GA, Rakoff-Nahoum S. The gut microbiome. Curr Biol, 2022, 32(6): R257-R264. doi: 10.1016/j.cub.2022.02.023.
37.	Zhou C, Zhao H, Xiao XY, et al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis. J Autoimmun, 2020, 107: 102360. doi: 10.1016/j.jaut.2019.102360.
38.	Primec M, Klemenak M, Di Gioia D, et al. Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids. Clin Nutr, 2019, 38(3): 1373-1381.
39.	Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, et al. Obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids. Cell Metab, 2020, 32(4): 548-560.
40.	Bashir M, Prietl B, Tauschmann M, et al. Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract. Eur J Nutr, 2016, 55(4): 1479-1489.
41.	Cervantes-Barragan L, Chai JN, Tianero MD, et al. Lactobacillus reuteri induces gut intraepithelial CD4⁺CD8αα⁺ T cells. Science, 2017, 357(6353): 806-810.
42.	Chen D, Jin D, Huang S, et al. Clostridium butyricum, a butyrate-producing probiotic, inhibits intestinal tumor development through modulating Wnt signaling and gut microbiota. Cancer Lett, 2020, 469: 456-467.
43.	Ma W, Mao Q, Xia W, et al. Gut microbiota shapes the efficiency of cancer therapy. Front Microbiol, 2019, 10: 1050. doi: 10.3389/fmicb.2019.01050.
44.	Sepich-Poore GD, Zitvogel L, Straussman R, et al. The microbiome and human cancer. Science, 2021, 371(6536): eabc4552. doi: 10.1126/science.abc4552.
45.	Yang W, Yu T, Huang X, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun, 2020, 11(1): 4457. doi: 10.1038/s41467-020-18262-6.
46.	Ogawa R, Yamamoto T, Hirai H, et al. Loss of SMAD4 promotes colorectal cancer progression by recruiting tumor-associated neutrophils via the CXCL1/8-CXCR2 axis. Clin Cancer Res, 2019, 25(9): 2887-2899.
47.	Zhang Y, Guoqiang L, Sun M, et al. Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment. Cancer Biol Med, 2020, 17(1): 32-43.
48.	Schneider KM, Mohs A, Gui W, 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.
49.	Albillos A, de Gottardi A, Rescigno M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol, 2020, 72(3): 558-577.
50.	Tripathi A, Debelius J, Brenner DA, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol, 2018, 15(7): 397-411.
51.	Shi L, Jin L, Huang W. Bile acids, intestinal barrier dysfunction, and related diseases. Cells, 2023, 12(14): 1888. doi: 10.3390/cells12141888.
52.	Enright EF, Griffin BT, Gahan CGM, et al. Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism. Pharmacol Res, 2018, 133: 170-186.
53.	Guzior DV, Quinn RA. Review: microbial transformations of human bile acids. Microbiome, 2021, 9(1): 140. doi: 10.1186/s40168-021-01101-1.
54.	Fiorucci S, Distrutti E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med, 2015, 21(11): 702-714.
55.	Lepercq P, Gérard P, Béguet F, et al. Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium baratii isolated from human feces. FEMS Microbiol Lett, 2004, 235(1): 65-72.
56.	Sannasiddappa TH, Lund PA, Clarke SR. In vitro antibacterial activity of unconjugated and conjugated bile salts on staphylococcus aureus. Front Microbiol, 2017, 8: 1581. doi: 10.3389/fmicb.2017.01581.
57.	Grüner N, Mattner J. Bile acids and microbiota: multifaceted and versatile regulators of the liver-gut axis. Int J Mol Sci, 2021, 22(3): 1397. doi: 10.3390/ijms22031397.
58.	Wu L, Feng J, Li J, et al. The gut microbiome-bile acid axis in hepatocarcinogenesis. Biomed Pharmacother, 2021, 133: 111036. doi: 10.1016/j.biopha.2020.111036.
59.	Schwabe RF, Greten TF. Gut microbiome in HCC—Mechanisms, diagnosis and therapy. J Hepatol, 2020, 72(2): 230-238.
60.	Rattan P, Minacapelli CD, Rustgi V. The microbiome and hepatocellular carcinoma. Liver Transpl, 2020, 26(10): 1316-1327.
61.	Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol, 2017, 17(4): 219-232.
62.	Guo X, Okpara ES, Hu W, et al. Interactive relationships between intestinal flora and bile acids. Int J Mol Sci, 2022, 23(15): 8343. doi: 10.3390/ijms23158343.
63.	Temraz S, Nassar F, Kreidieh F, et al. Hepatocellular carcinoma immunotherapy and the potential influence of gut microbiome. Int J Mol Sci, 2021, 22(15): 7800. doi: 10.3390/ijms22157800.
64.	Chen W, Wen L, Bao Y, et al. Gut flora disequilibrium promotes the initiation of liver cancer by modulating tryptophan metabolism and up-regulating SREBP2. Proc Natl Acad Sci U S A, 2022, 119(52): e2203894119. doi: 10.1073/pnas.2203894119.
65.	Huang H, Ren Z, Gao X, et al. Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma. Genome Med, 2020, 12(1): 102. doi: 10.1186/s13073-020-00796-5.
66.	Ren Z, Li A, Jiang J, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut, 2019, 68(6): 1014-1023.
67.	Yang J, He Q, Lu F, et al. A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma. Gut Microbes, 2023, 15(1): 2201159. doi: 10.1080/19490976.2023.2201159.
68.	Qiao Y, Wang J, Karagoz E, et al. Axis inhibition protein 1 (Axin1) deletion-induced hepatocarcinogenesis requires intact β-Catenin but not notch cascade in mice. Hepatology, 2019, 70(6): 2003-2017.
69.	Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, et al. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature, 2019, 570(7762): 462-467.
70.	Li Z, Zhang Y, Hong W, et al. Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma via STING signaling. Gut Microbes, 2022, 14(1): 2119055. doi: 10.1080/19490976.2022.2119055.
71.	皮丽娜, 候艳莹, 张维. 肠道菌群失调、炎症因子变化、维生素缺乏与肝癌患者根治术后复发的关系. 现代肿瘤医学, 2019, 27(17): 3078-3081.
72.	Garrett WS. Cancer and the microbiota. Science, 2015, 348(6230): 80-86.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. Kuo CL, Chou HY, Chiu YC, et al. Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis. Cancer Lett, 2020, 474: 138-150.
3. Li W, Wang H, Ma Z, et al. Multi-omics analysis of microen-vironment characteristics and immune escape mechanisms of hepatocellular carcinoma. Front Oncol, 2019, 9: 1019. doi: 10.3389/fonc.2019.01019.
4. Martínez-Reyes I, Chandel NS. Cancer metabolism: looking forward. Nat Rev Cancer, 2021, 21(10): 669-680.
5. Yang X, Guo Y, Chen C, et al. Interaction between intestinal microbiota and tumour immunity in the tumour microen-vironment. Immunology, 2021, 164(3): 476-493.
6. Xiao Y, Yu D. Tumor microenvironment as a therapeutic target in cancer. Pharmacol Ther, 2021, 221: 107753. doi: 10.1016/j.pharmthera.2020.107753.
7. Nejman D, Livyatan I, Fuks G, et al. The human tumor microbiome is composed of tumor type-specific intracellular bacteria. Science, 2020, 368(6494): 973-980.
8. Qiu Q, Lin Y, Ma Y, et al. Exploring the emerging role of the gut microbiota and tumor microenvironment in cancer immunotherapy. Front Immunol, 2021, 11: 612202. doi: 10.3389/fimmu.2020.612202.
9. Chen C, Wang Z, Ding Y, et al. Tumor microenvironment-mediated immune evasion in hepatocellular carcinoma. Front Immunol, 2023, 14: 1133308. doi: 10.3389/fimmu.2023.1133308.
10. Doroshow DB, Bhalla S, Beasley MB, et al. PD-L1 as a biomarker of response to immune-checkpoint inhibitors. Nat Rev Clin Oncol, 2021, 18(6): 345-362.
11. Tang T, Huang X, Zhang G, et al. Advantages of targeting the tumor immune microenvironment over blocking immune checkpoint in cancer immunotherapy. Signal Transduct Target Ther, 2021, 6(1): 72. doi: 10.1038/s41392-020-00449-4.
12. Narunsky-Haziza L, Sepich-Poore GD, Livyatan I, et al. Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions. Cell, 2022, 185(20): 3789-3806.
13. Neuzillet C, Marchais M, Vacher S, et al. Prognostic value of intratumoral Fusobacterium nucleatum and association with immune-related gene expression in oral squamous cell carcinoma patients. Sci Rep, 2021, 11(1): 7870. doi: 10.1038/s41598-021-86816-9.
14. Kohi S, Macgregor-Das A, Dbouk M, et al. Alterations in the duodenal fluid microbiome of patients with pancreatic cancer. Clin Gastroenterol Hepatol, 2022, 20(2): e196-e227. doi: 10.1016/j.cgh.2020.11.006.
15. Xie Y, Xie F, Zhou X, et al. Microbiota in tumors: from understanding to application. Adv Sci (Weinh), 2022, 9(21): e2200470. doi: 10.1002/advs.202200470.
16. Bertocchi A, Carloni S, Ravenda PS, et al. Gut vascular barrier impairment leads to intestinal bacteria dissemination and colorectal cancer metastasis to liver. Cancer Cell, 2021, 39(5): 708-724.
17. Chen Y, Liu B, Wei Y, et al. Influence of gut and intratumoral microbiota on the immune microenvironment and anti-cancer therapy. Pharmacol Res, 2021, 174: 105966. doi: 10.1016/j.phrs.2021.105966.
18. Fu A, Yao B, Dong T, et al. Emerging roles of intratumor microbiota in cancer metastasis. Trends Cell Biol, 2023, 33(7): 583-593.
19. Sas Z, Cendrowicz E, Weinhäuser I, et al. Tumor microenvironment of hepatocellular carcinoma: challenges and opportunities for new treatment options. Int J Mol Sci, 2022, 23(7): 3778. doi: 10.3390/ijms23073778.
20. Yang Q, Guo N, Zhou Y, et al. The role of tumor-associated macrophages (TAMs) in tumor progression and relevant advance in targeted therapy. Acta Pharm Sin B, 2020, 10(11): 2156-2170.
21. Pavlović N, Calitz C, Thanapirom K, et al. Inhibiting IRE1α-endonuclease activity decreases tumor burden in a mouse model for hepatocellular carcinoma. Elife, 2020, 9: e55865. doi: 10.7554/eLife.55865.
22. Yuen VW, Wong CC. Hypoxia-inducible factors and innate immunity in liver cancer. J Clin Invest, 2020, 130(10): 5052-5062.
23. Kudo M. Scientific rationale for combined immunotherapy with PD-1/PD-L1 antibodies and VEGF inhibitors in advanced hepatocellular carcinoma. Cancers (Basel), 2020, 12(5): 1089. doi: 10.3390/cancers12051089.
24. Wu Z, Li S, Zhu X. The mechanism of stimulating and mobilizing the immune system enhancing the anti-tumor immunity. Front Immunol, 2021, 12: 682435. doi: 10.3389/fimmu.2021.682435.
25. El-Serag HB, Rudolph KL. Hepatocellular carcinoma: epidemiology and molecular carcinogenesis. Gastroenterology, 2007, 132(7): 2557-2576.
26. Boedtkjer E, Pedersen SF. The acidic tumor microenvironment as a driver of cancer. Annu Rev Physiol, 2020, 82: 103-126.
27. Gao X, Huang H, Wang Y, et al. Tumor immune microen-vironment characterization in hepatocellular carcinoma identifies four prognostic and immunotherapeutically relevant subclasses. Front Oncol, 2021, 10: 610513. doi: 10.3389/fonc.2020.610513.
28. Huang Y, Fan XG, Wang ZM, et al. Identification of helicobacter species in human liver samples from patients with primary hepatocellular carcinoma. J Clin Pathol, 2004, 57(12): 1273-1277.
29. Qu D, Wang Y, Xia Q, et al. Intratumoral microbiome of human primary liver cancer. Hepatol Commun, 2022, 6(7): 1741-1752.
30. Liu B, Zhou Z, Jin Y, et al. Hepatic stellate cell activation and senescence induced by intrahepatic microbiota disturbances drive progression of liver cirrhosis toward hepatocellular carcinoma. J Immunother Cancer, 2022, 10(1): e003069. doi: 10.1136/jitc-2021-003069.
31. Poore GD, Kopylova E, Zhu Q, et al. Microbiome analyses of blood and tissues suggest cancer diagnostic approach. Nature, 2020, 579(7800): 567-574.
32. Xue C, Chu Q, Zheng Q, et al. Current understanding of the intratumoral microbiome in various tumors. Cell Rep Med, 2023, 4(1): 100884. doi: 10.1016/j.xcrm.2022.100884.
33. Zhang YJ, Li S, Gan RY, et al. Impacts of gut bacteria on human health and diseases. Int J Mol Sci, 2015, 16(4): 7493-7519.
34. Fan Y, Pedersen O. Gut microbiota in human metabolic health and disease. Nat Rev Microbiol, 2021, 19(1): 55-71.
35. Ding RX, Goh WR, Wu RN, et al. Revisit gut microbiota and its impact on human health and disease. J Food Drug Anal, 2019, 27(3): 623-631.
36. Kuziel GA, Rakoff-Nahoum S. The gut microbiome. Curr Biol, 2022, 32(6): R257-R264. doi: 10.1016/j.cub.2022.02.023.
37. Zhou C, Zhao H, Xiao XY, et al. Metagenomic profiling of the pro-inflammatory gut microbiota in ankylosing spondylitis. J Autoimmun, 2020, 107: 102360. doi: 10.1016/j.jaut.2019.102360.
38. Primec M, Klemenak M, Di Gioia D, et al. Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids. Clin Nutr, 2019, 38(3): 1373-1381.
39. Arnoriaga-Rodríguez M, Mayneris-Perxachs J, Burokas A, et al. Obesity impairs short-term and working memory through gut microbial metabolism of aromatic amino acids. Cell Metab, 2020, 32(4): 548-560.
40. Bashir M, Prietl B, Tauschmann M, et al. Effects of high doses of vitamin D3 on mucosa-associated gut microbiome vary between regions of the human gastrointestinal tract. Eur J Nutr, 2016, 55(4): 1479-1489.
41. Cervantes-Barragan L, Chai JN, Tianero MD, et al. Lactobacillus reuteri induces gut intraepithelial CD4⁺CD8αα⁺ T cells. Science, 2017, 357(6353): 806-810.
42. Chen D, Jin D, Huang S, et al. Clostridium butyricum, a butyrate-producing probiotic, inhibits intestinal tumor development through modulating Wnt signaling and gut microbiota. Cancer Lett, 2020, 469: 456-467.
43. Ma W, Mao Q, Xia W, et al. Gut microbiota shapes the efficiency of cancer therapy. Front Microbiol, 2019, 10: 1050. doi: 10.3389/fmicb.2019.01050.
44. Sepich-Poore GD, Zitvogel L, Straussman R, et al. The microbiome and human cancer. Science, 2021, 371(6536): eabc4552. doi: 10.1126/science.abc4552.
45. Yang W, Yu T, Huang X, et al. Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity. Nat Commun, 2020, 11(1): 4457. doi: 10.1038/s41467-020-18262-6.
46. Ogawa R, Yamamoto T, Hirai H, et al. Loss of SMAD4 promotes colorectal cancer progression by recruiting tumor-associated neutrophils via the CXCL1/8-CXCR2 axis. Clin Cancer Res, 2019, 25(9): 2887-2899.
47. Zhang Y, Guoqiang L, Sun M, et al. Targeting and exploitation of tumor-associated neutrophils to enhance immunotherapy and drug delivery for cancer treatment. Cancer Biol Med, 2020, 17(1): 32-43.
48. Schneider KM, Mohs A, Gui W, 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.
49. Albillos A, de Gottardi A, Rescigno M. The gut-liver axis in liver disease: Pathophysiological basis for therapy. J Hepatol, 2020, 72(3): 558-577.
50. Tripathi A, Debelius J, Brenner DA, et al. The gut-liver axis and the intersection with the microbiome. Nat Rev Gastroenterol Hepatol, 2018, 15(7): 397-411.
51. Shi L, Jin L, Huang W. Bile acids, intestinal barrier dysfunction, and related diseases. Cells, 2023, 12(14): 1888. doi: 10.3390/cells12141888.
52. Enright EF, Griffin BT, Gahan CGM, et al. Microbiome-mediated bile acid modification: Role in intestinal drug absorption and metabolism. Pharmacol Res, 2018, 133: 170-186.
53. Guzior DV, Quinn RA. Review: microbial transformations of human bile acids. Microbiome, 2021, 9(1): 140. doi: 10.1186/s40168-021-01101-1.
54. Fiorucci S, Distrutti E. Bile acid-activated receptors, intestinal microbiota, and the treatment of metabolic disorders. Trends Mol Med, 2015, 21(11): 702-714.
55. Lepercq P, Gérard P, Béguet F, et al. Epimerization of chenodeoxycholic acid to ursodeoxycholic acid by Clostridium baratii isolated from human feces. FEMS Microbiol Lett, 2004, 235(1): 65-72.
56. Sannasiddappa TH, Lund PA, Clarke SR. In vitro antibacterial activity of unconjugated and conjugated bile salts on staphylococcus aureus. Front Microbiol, 2017, 8: 1581. doi: 10.3389/fmicb.2017.01581.
57. Grüner N, Mattner J. Bile acids and microbiota: multifaceted and versatile regulators of the liver-gut axis. Int J Mol Sci, 2021, 22(3): 1397. doi: 10.3390/ijms22031397.
58. Wu L, Feng J, Li J, et al. The gut microbiome-bile acid axis in hepatocarcinogenesis. Biomed Pharmacother, 2021, 133: 111036. doi: 10.1016/j.biopha.2020.111036.
59. Schwabe RF, Greten TF. Gut microbiome in HCC—Mechanisms, diagnosis and therapy. J Hepatol, 2020, 72(2): 230-238.
60. Rattan P, Minacapelli CD, Rustgi V. The microbiome and hepatocellular carcinoma. Liver Transpl, 2020, 26(10): 1316-1327.
61. Levy M, Kolodziejczyk AA, Thaiss CA, et al. Dysbiosis and the immune system. Nat Rev Immunol, 2017, 17(4): 219-232.
62. Guo X, Okpara ES, Hu W, et al. Interactive relationships between intestinal flora and bile acids. Int J Mol Sci, 2022, 23(15): 8343. doi: 10.3390/ijms23158343.
63. Temraz S, Nassar F, Kreidieh F, et al. Hepatocellular carcinoma immunotherapy and the potential influence of gut microbiome. Int J Mol Sci, 2021, 22(15): 7800. doi: 10.3390/ijms22157800.
64. Chen W, Wen L, Bao Y, et al. Gut flora disequilibrium promotes the initiation of liver cancer by modulating tryptophan metabolism and up-regulating SREBP2. Proc Natl Acad Sci U S A, 2022, 119(52): e2203894119. doi: 10.1073/pnas.2203894119.
65. Huang H, Ren Z, Gao X, et al. Integrated analysis of microbiome and host transcriptome reveals correlations between gut microbiota and clinical outcomes in HBV-related hepatocellular carcinoma. Genome Med, 2020, 12(1): 102. doi: 10.1186/s13073-020-00796-5.
66. Ren Z, Li A, Jiang J, et al. Gut microbiome analysis as a tool towards targeted non-invasive biomarkers for early hepatocellular carcinoma. Gut, 2019, 68(6): 1014-1023.
67. Yang J, He Q, Lu F, et al. A distinct microbiota signature precedes the clinical diagnosis of hepatocellular carcinoma. Gut Microbes, 2023, 15(1): 2201159. doi: 10.1080/19490976.2023.2201159.
68. Qiao Y, Wang J, Karagoz E, et al. Axis inhibition protein 1 (Axin1) deletion-induced hepatocarcinogenesis requires intact β-Catenin but not notch cascade in mice. Hepatology, 2019, 70(6): 2003-2017.
69. Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, et al. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature, 2019, 570(7762): 462-467.
70. Li Z, Zhang Y, Hong W, et al. Gut microbiota modulate radiotherapy-associated antitumor immune responses against hepatocellular carcinoma via STING signaling. Gut Microbes, 2022, 14(1): 2119055. doi: 10.1080/19490976.2022.2119055.
71. 皮丽娜, 候艳莹, 张维. 肠道菌群失调、炎症因子变化、维生素缺乏与肝癌患者根治术后复发的关系. 现代肿瘤医学, 2019, 27(17): 3078-3081.
72. Garrett WS. Cancer and the microbiota. Science, 2015, 348(6230): 80-86.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Intestinal flora affects occurrence of hepatocellular carcinoma by regulating tumor microenvironment

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