College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China.
Biomed Res Int. 2019 Jun 17;2019:8020785. doi: 10.1155/2019/8020785. eCollection 2019.
The intestinal microbiome plays a crucial role in promoting intestinal health, and perturbations to its constitution may result in chronic intestinal inflammation and lead to colorectal cancer (CRC). -Ketoglutarate is an important intermediary in the NF-B-mediated inflammatory pathway that maintains intestinal homeostasis and prevents initiation of intestinal inflammation, a known precursor to carcinoma development. The objective of this study was to assess the potential protective effects of -ketoglutarate intervention against CRC development, which may arise due to its known anti-inflammatory and antitumour effects. CRC was induced in C57BL/6 mice using azoxymethane (AOM) and dextran sulfate sodium (DSS). Tumour frequency, histological rating, and colonic microbiota were assessed in colonic samples. The findings demonstrated that -ketoglutarate offered significant protection against CRC development in mice. Furthermore, -ketoglutarate also exhibited immunomodulatory effects mediated via downregulation of interleukin (IL)-6, IL-22, tumour necrosis factor (TNF)-, and IL-1 cytokines. Finally, intervention with -ketoglutarate tended to minimise the frequency of opportunistic pathogens ( and ) while increasing the populations of , and . Taken together, our findings show that dietary -ketoglutarate intervention may protect against inflammation-related CRC.
肠道微生物群在促进肠道健康方面发挥着关键作用，其组成的紊乱可能导致慢性肠道炎症，并导致结直肠癌（CRC）。-酮戊二酸是 NF-B 介导的炎症途径中的重要中间产物，可维持肠道内稳态并防止肠道炎症的发生，而后者是癌前病变的已知诱因。本研究旨在评估 -酮戊二酸干预对 CRC 发展的潜在保护作用，这可能是由于其已知的抗炎和抗肿瘤作用。本研究采用氧化偶氮甲烷（AOM）和葡聚糖硫酸钠（DSS）诱导 C57BL/6 小鼠发生 CRC。评估结肠样本中的肿瘤发生率、组织学评分和结肠微生物群。结果表明，-酮戊二酸为小鼠提供了对 CRC 发展的显著保护。此外，-酮戊二酸还通过下调白细胞介素（IL）-6、IL-22、肿瘤坏死因子（TNF）- 和 IL-1 细胞因子发挥免疫调节作用。最后，-酮戊二酸的干预倾向于最小化机会性病原体（ 和 ）的频率，同时增加 、 和 的数量。综上所述，我们的研究结果表明，饮食干预 -酮戊二酸可能有助于预防与炎症相关的 CRC。
