Loss of SIRT5 promotes bile acid-induced immunosuppressive microenvironment and hepatocarcinogenesis

Sun, Renqiang; Zhang, Zhiyong; Bao, Ruoxuan; Guo, Xiaozhen; Gu, Yuan; Yang, Wenjing; Wei, Jinsong; Chen, Xinyu; Tong, Lingfeng; Meng, Jian; Zhong, Cheng; Zhang, Cheng; Zhang, Jinye; Sun, Yiping; Chen, Ling; Tong, Xuemei; Yu, Fa‐Xing; Yu, Hongxiu; Qu, Wei‐Feng; Zhao, Bin; Guo, Wei; Qian, Maoxiang; Saiyin, Hexige; Liu, Ying; Liu, Ronghua; Xie, Cen; Liu, Weiren; Xiong, Yue; Guan, Kun‐Liang; Shi, Ying‐Hong; Wang, Pu; Ye, Dan

doi:10.1016/j.jhep.2022.02.030

Cited by 73 publications

(52 citation statements)

References 47 publications

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“…53 SIRT5 deficiency increases BA-induced immunosuppressive microenvironments in the liver. 54 The present study demonstrated that LPS challenge reduced the expression of the ileal SIRT5 gene and protein, whereas CUR had the reverse effects. Previous research also demonstrated that CUR activated mitochondrial biogenesis to counteract LPS-induced mitochondrial dysfunction.…”

Section: Discussionsupporting

confidence: 47%

Curcumin alleviates LPS-induced intestinal homeostatic imbalance through reshaping gut microbiota structure and regulating group 3 innate lymphoid cells in chickens

Ruan

Fouad

et al. 2022

Food Funct.

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Section: Discussionsupporting

confidence: 47%

Curcumin alleviates LPS-induced intestinal homeostatic imbalance through reshaping gut microbiota structure and regulating group 3 innate lymphoid cells in chickens

Ruan

Fouad

et al. 2022

Food Funct.

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“…A recent study found that the decreased expression of SITR5 in hepatocellular carcinoma patients leads to increased bile acid synthesis. Bile acids act as signaling molecules to stimulate their nuclear receptors and promote the polarization of M2-type macrophages, thereby creating an immunosuppressive tumor microenvironment and promoting tumor growth ( 30 ). It is reasonable to infer that bile acids play a role in the occurrence and development of biliary tract tumors by interacting with the immune system.…”

Section: Introductionmentioning

confidence: 99%

Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers

Liu

et al. 2022

Front. Immunol.

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Biliary tract cancers (BTCs), including cholangiocarcinoma and gallbladder carcinoma, originate from the biliary epithelium and have a poor prognosis. Surgery is the only choice for cure in the early stage of disease. However, most patients are diagnosed in the advanced stage and lose the chance for surgery. Early diagnosis could significantly improve the prognosis of patients. Bile has complex components and is in direct contact with biliary tract tumors. Bile components are closely related to the occurrence and development of biliary tract tumors and may be applied as biomarkers for BTCs. Meanwhile, arising evidence has confirmed the immunoregulatory role of bile components. In this review, we aim to summarize and discuss the relationship between bile components and biliary tract cancers and their ability as biomarkers for BTCs, highlighting the role of bile components in regulating immune response, and their promising application prospects.

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“…The role of BAs in immune cell-mediated CRC progression remains undetermined, and the effects of BAs on macrophages and T cells have been reported to affect liver cancer. TCA can induce macrophages polarization into M2–like phenotype and facilitated immunosuppressive TME formation that favors to liver tumor growth [ 59 ]. Recruitment of neutrophils and inflammatory monocytes also contributed to the CRC metastasis [ 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

A High Hepatic Uptake of Conjugated Bile Acids Promotes Colorectal Cancer—Associated Liver Metastasis

Zheng

Wei

Hou

et al. 2022

Cells

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The liver is the most common site for colorectal cancer (CRC)–associated metastasis. There remain unsatisfactory medications in liver metastasis given the incomplete understanding of pathogenic mechanisms. Herein, with an orthotopic implantation model fed either regular or high-fat diets (HFD), more liver metastases were associated with an expansion of conjugated bile acids (BAs), particularly taurocholic acid (TCA) in the liver, and an increased gene expression of Na+–taurocholate cotransporting polypeptide (NTCP). Such hepatic BA change was more apparently shown in the HFD group. In the same model, TCA was proven to promote liver metastases and induce a tumor-favorable microenvironment in the liver, characterizing a high level of fibroblast activation and increased proportions of myeloid-derived immune cells. Hepatic stellate cells, a liver-residing source of fibroblasts, were dose-dependently activated by TCA, and their conditioned medium significantly enhanced the migration capability of CRC cells. Blocking hepatic BA uptake with NTCP neutralized antibody can effectively repress TCA–triggered liver metastases, with an evident suppression of tumor microenvironment niche formation. This study points to a new BA–driven mechanism of CRC–associated liver metastases, suggesting that a reduction of TCA overexposure by limiting liver uptake is a potential therapeutic option for CRC—associated liver metastasis.

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Loss of SIRT5 promotes bile acid-induced immunosuppressive microenvironment and hepatocarcinogenesis

Cited by 73 publications

References 47 publications

Curcumin alleviates LPS-induced intestinal homeostatic imbalance through reshaping gut microbiota structure and regulating group 3 innate lymphoid cells in chickens

Curcumin alleviates LPS-induced intestinal homeostatic imbalance through reshaping gut microbiota structure and regulating group 3 innate lymphoid cells in chickens

Research progress of bile biomarkers and their immunoregulatory role in biliary tract cancers

A High Hepatic Uptake of Conjugated Bile Acids Promotes Colorectal Cancer—Associated Liver Metastasis

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