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Review
. 2023 Aug 29:14:1252616.
doi: 10.3389/fimmu.2023.1252616. eCollection 2023.

Insights into vitamin A in bladder cancer, lack of attention to gut microbiota?

Peiyue Luo  1   2   3 , Liying Zheng  4 , Junrong Zou  2   3 , Tao Chen  1   2   3 , Jun Zou  1   2   3 , Wei Li  1   2   3 , Qi Chen  1   2   3 , Biao Qian  2   3
Affiliations
Review

Insights into vitamin A in bladder cancer, lack of attention to gut microbiota?

Peiyue Luo et al. Front Immunol. .

Abstract

Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over the years. However, the effectiveness of these strategies in clinical practice has not met expectations, and they have not been widely adopted. Recent medical research on intestinal flora has revealed that bladder cancer patients exhibit reduced serum vitamin A levels and an imbalance of gut microbiota. In light of the close relationship between gut microbiota and vitamin A, one can speculate that a complex regulatory mechanism exists between the two in the development and occurrence of bladder cancer. As such, further exploration of their interaction in bladder cancer may help guide the use of vitamin A for preventive purposes. During the course of this review, attention is paid to the influence of intestinal microbiota on the vitamin A metabolism and the RA signaling pathway, as well as the mutual promotion relationships between them in the prevention of bladder cancer, In addition, it emphasizes the importance of intestinal microbiota for bladder cancer prevention and treatment.

Keywords: bladder cancer; gut microbiota; lipopolysaccharides; retinoic acid; vitamin A.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Vitamin A absorption. Various animal-derived vitamin A is first converted into retinol in the gastrointestinal tract, then absorbed into the blood through the intestine, combined with RBP4 for transport in the blood, and finally transported to the liver for storage. A part of phytogenic vitamin A can be converted into retinol by β-carotene oxygenase and absorbed, and the other part can be integrated into chylomicron with retinol and enter the blood circulation through lymphatic reflux. RBP4, retinol-binding protein 4; GM, gut microbiota.
Figure 2
Figure 2
Retinoic acid metabolism. Retinol, β-carotene and chylomicron enter target cells through specific receptors and are transformed into the most active RA after a multi-step enzymatic reaction. RA binds different protein transporters and then interacts with different receptors. It also binds to CRABP and is transported to the RAR/RXR dimer to activate transcription, which can regulate the expression of genes such as cell proliferation and metabolism. In addition, RAs that are not transported to the nucleus are eventually degraded by CYP26 and lose functional activity. RBP4, retinol-binding protein 4; STRA6, stimulated by retinoic acid gene 6 protein; LRAT, lecithin retinol acyltransferase; RDHs, retinol dehydrogenases; ALDHs, aldehyde dehydrogenases; RA, retinoic acid; FAB5, fatty acid binding protein; CRABP, cellular retinol-binding proteins; PPAR, peroxisome proliferator activating receptor; RAR, retinoic acid receptor; CYP26, cytochrome P450 family 26.
Figure 3
Figure 3
Mechanism of gut microbiota mediating tumor development. 1. The gut microbiota induces chronic inflammation by activating the NF-kB or STAT3 pathways and various tumorigenic-related pathways. 2. Abnormal signaling pathways TNF/IL-8 and Wnt/β-catenin promote the metastasis and invasion of tumor cells. 3. The gut microbiota induces DNA damage and cell proliferation. 4. Gut microbiota recruit MDSCs release active mediators, thus mediating immunosuppression and promoting tumorigenesis. 5. The gut microbiota can change the content of various metabolites. For example, SCFA can induce the differentiation of macrophages and inhibit the NF-kB pathway, while bile acids can activate multiple pathways to affect the tumor microenvironment and the occurrence and development of tumors. DC, dendritic cell; SCFA, short-chain fatty acid; MDSC, myeloid-derived suppressor cells.
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References

    1. Lobo N, Afferi L, Moschini M, Mostafid H, Porten S, Psutka SP, et al. . Epidemiology, screening, and prevention of bladder cancer. Eur Urol Oncol (2022) 5(6):628–39. doi: 10.1016/j.euo.2022.10.003 - DOI - PubMed
    1. Cumberbatch MGK, Jubber I, Black PC, Esperto F, Figueroa JD, Kamat AM, et al. . Epidemiology of bladder cancer: A systematic review and contemporary update of risk factors in 2018. Eur Urol (2018) 74(6):784–95. doi: 10.1016/j.eururo.2018.09.001 - DOI - PubMed
    1. Li Y, Zhang H, Guo Y, Cai H, Li X, He J, et al. . A qualitative transcriptional signature for predicting recurrence risk of stage I-III bladder cancer patients after surgical resection. Front Oncol (2019) 9:629. doi: 10.3389/fonc.2019.00629 - DOI - PMC - PubMed
    1. Catto JWF, Downing A, Mason S, Wright P, Absolom K, Bottomley S, et al. . Quality of life after bladder cancer: A cross-sectional survey of patient-reported outcomes. Eur Urol (2021) 79(5):621–32. doi: 10.1016/j.eururo.2021.01.032 - DOI - PMC - PubMed
    1. de Thé H, Chomienne C, Lanotte M, Degos L, Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor alpha gene to a novel transcribed locus. Nature (1990) 347(6293):558–61. doi: 10.1038/347558a0 - DOI - PubMed

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Grants and funding

This work was supported by the Health Commission Research Project of China (No. HDSL202001057), the Jiangxi Provincial Health Commission Research Project (No. SKJP20203656), and the Jiangxi Province 2021 Postgraduate Innovation Special Fund Project (No. YC2022-S959).