Abstract：
BACKGROUND: The intake of high-fructose corn syrup (HFCS) may increase the risk of colorectal cancer (CRC). This study aimed to explore the potential effects and mechanisms of resistant starch (RS) in HFCS-induced colon tumorigenesis.
METHODS: The azoxymethane/dextran sodium sulfate (AOM/DSS) and ApcMin/+ mice models were used to investigate the roles of HFCS and RS in CRC in vivo. An immunohistochemistry (IHC) staining analysis was used to detect the expression of proliferation-related proteins in tissues. 16S rRNA sequencing for microbial community, gas chromatography for short-chain fatty acids (SCFAs), and mass spectrometry analysis for glycolysis products in the intestines were performed. Furthermore, lactic acid assay kit was used to detect the glycolysis levels in vitro.
RESULTS: RS suppressed HFCS-induced colon tumorigenesis through reshaping the microbial community. Mechanistically, the alteration of the microbial community after RS supplement increased the levels of intestinal SCFAs, especially butyrate, leading to the suppression of glycolysis and CRC cell proliferation by downregulating HK2.
CONCLUSIONS: Our study identified RS as a candidate of protective factors in CRC and may provide a potential target for HFCS-related CRC treatment.
METHODS: The azoxymethane/dextran sodium sulfate (AOM/DSS) and ApcMin/+ mice models were used to investigate the roles of HFCS and RS in CRC in vivo. An immunohistochemistry (IHC) staining analysis was used to detect the expression of proliferation-related proteins in tissues. 16S rRNA sequencing for microbial community, gas chromatography for short-chain fatty acids (SCFAs), and mass spectrometry analysis for glycolysis products in the intestines were performed. Furthermore, lactic acid assay kit was used to detect the glycolysis levels in vitro.
RESULTS: RS suppressed HFCS-induced colon tumorigenesis through reshaping the microbial community. Mechanistically, the alteration of the microbial community after RS supplement increased the levels of intestinal SCFAs, especially butyrate, leading to the suppression of glycolysis and CRC cell proliferation by downregulating HK2.
CONCLUSIONS: Our study identified RS as a candidate of protective factors in CRC and may provide a potential target for HFCS-related CRC treatment.
摘要：
背景：摄入高果糖玉米糖浆（HFCS）可能会增加结直肠癌（CRC）的风险。本研究旨在探讨抗性淀粉(RS)在HFCS诱导的结肠肿瘤发生中的潜在作用及其机制。
方法：采用偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）和ApcMin/+小鼠模型研究HFCS和RS在CRC中的作用。免疫组织化学(IHC)染色分析用于检测组织中增殖相关蛋白的表达。微生物群落的16SrRNA测序，短链脂肪酸(SCFA)的气相色谱法，并对肠道中的糖酵解产物进行质谱分析。此外，用乳酸检测试剂盒检测体外糖酵解水平。
结果：RS通过重塑微生物群落抑制HFCS诱导的结肠肿瘤发生。机械上,补充RS后微生物群落的改变增加了肠道SCFA的水平，尤其是丁酸,通过下调HK2来抑制糖酵解和CRC细胞增殖。
结论：我们的研究将RS确定为CRC保护因子的候选因子，并可能为HFCS相关CRC治疗提供潜在靶点。
方法：采用偶氮甲烷/葡聚糖硫酸钠（AOM/DSS）和ApcMin/+小鼠模型研究HFCS和RS在CRC中的作用。免疫组织化学(IHC)染色分析用于检测组织中增殖相关蛋白的表达。微生物群落的16SrRNA测序，短链脂肪酸(SCFA)的气相色谱法，并对肠道中的糖酵解产物进行质谱分析。此外，用乳酸检测试剂盒检测体外糖酵解水平。
结果：RS通过重塑微生物群落抑制HFCS诱导的结肠肿瘤发生。机械上,补充RS后微生物群落的改变增加了肠道SCFA的水平，尤其是丁酸,通过下调HK2来抑制糖酵解和CRC细胞增殖。
结论：我们的研究将RS确定为CRC保护因子的候选因子，并可能为HFCS相关CRC治疗提供潜在靶点。
