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一种肠道产丁酸细菌调节短链脂肪酸转运体和受体以减缓1,2 - 二甲基肼相关结直肠癌的进展。

A gut butyrate-producing bacterium regulates short-chain fatty acid transporter and receptor to reduce the progression of 1,2-dimethylhydrazine-associated colorectal cancer.

作者信息

Chang Shih-Chang, Shen Ming-Hung, Liu Chih-Yi, Pu Chi-Ming, Hu Je-Ming, Huang Chi-Jung

机构信息

Division of Colorectal Surgery, Department of Surgery, Cathay General Hospital, Taipei 10630, Taiwan, R.O.C.

Department of Surgery, Fu Jen Catholic University Hospital, New Taipei City 24352, Taiwan, R.O.C.

出版信息

Oncol Lett. 2020 Dec;20(6):327. doi: 10.3892/ol.2020.12190. Epub 2020 Oct 5.

Abstract

Gut microbes influence tumor development and progression in the intestines and may provide a novel paradigm for the treatment of colorectal cancer (CRC). Gut dysbiosis may be associated with the development and progression of CRC. Identifying the interactions between the colonic tract and gut microbiota may provide novel information relevant to CRC prevention. The present study examined the effects of butyrate-producing () on mice with 1,2-dimethylhydrazine (DMH)-induced CRC and the microbial metabolite of on CRC cells. Immunohistochemical staining of the mouse colon tissues and reverse transcription PCR of CRC cells were used to determine the protein and mRNA expression levels of the short-chain fatty acid (SCFA) transporter solute carrier family 5 member 8 (SLC5A8) and G-protein-coupled receptor 43 (GPR43). In CRC-bearing mice fed , DMH-induced CRC regressed, body weight increased and serum carcinoembryonic antigen levels decreased. Notably, SLC5A8 and GPR43 were diffusely and moderately to strongly expressed in the neoplastic epithelial cells and underlying muscularis propria in the colons of the mice. In conclusion, administration of or its metabolites improved the clinical outcome of CRC by activating the SCFA transporter and/or receptor. These results indicated that was a probiotic with anti-CRC potential.

摘要

肠道微生物影响肠道肿瘤的发生和进展,可能为结直肠癌(CRC)的治疗提供新的范例。肠道微生物群失调可能与CRC的发生和进展有关。确定结肠与肠道微生物群之间的相互作用可能为CRC预防提供新的相关信息。本研究检测了产丁酸菌对1,2 - 二甲基肼(DMH)诱导的CRC小鼠的影响以及其微生物代谢产物对CRC细胞的影响。采用小鼠结肠组织免疫组化染色和CRC细胞逆转录PCR法,检测短链脂肪酸(SCFA)转运体溶质载体家族5成员8(SLC5A8)和G蛋白偶联受体43(GPR43)的蛋白和mRNA表达水平。在喂食产丁酸菌的荷CRC小鼠中,DMH诱导的CRC消退,体重增加,血清癌胚抗原水平降低。值得注意的是,SLC5A8和GPR43在小鼠结肠的肿瘤上皮细胞和固有肌层中呈弥漫性、中度至强表达。总之,给予产丁酸菌或其代谢产物可通过激活SCFA转运体和/或受体改善CRC的临床结局。这些结果表明产丁酸菌是一种具有抗CRC潜力的益生菌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61c/7577080/17a5f6e7b6dd/ol-20-06-12190-g00.jpg

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