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Dietary inclusion of nitrite-containing frankfurter exacerbates colorectal cancer pathology, alters metabolism and causes gut dybiosis in APCmin mice
bioRxiv - Biochemistry Pub Date : 2022-11-25 , DOI: 10.1101/2022.03.17.484445
William Crowe , Xiaobei Pan , James Mackle , Adam Harris , Gary Hardiman , Chris T Elliott , Brian D Green

Colorectal cancer (CRC) is the second most prevalent malignancy in Europe and diet is an important modifiable risk factor. Processed meat consumption, including meats with preservative salts such as sodium nitrite, have been implicated in CRC pathogenesis. This study investigated how the CRC pathology and metabolic status of adenomatous polyposis coli (APC) multiple intestinal neoplasia (min) mice was perturbed following 8 weeks of pork meat consumption. Dietary inclusions (15%) of either nitrite-free pork, nitrite-free sausage or nitrite-containing sausage (frankfurter) were compared against a parallel control group (100% chow). Comprehensive studies investigated: gastrointestinal tract histology (tumours, aberrant crypt foci (ACF) and mucin deplin foci (MDF), lipid peroxidation (urine and serum), faecal microbiota and serum metabolomics (599 metabolites). After 8 weeks mice consuming the frankfurter diet had 53% more (P=0.014) gastrointestinal tumours than control, although ACF and MDF did not differ. Urine and serum lipid peroxidation markers were 59% (P=0.001) and 108% (P=0.001) higher, respectively in the frankfurter group. Gut dysbiosis was evident in these mice with comparably fewer Bacteriodes and more Firmicutes. Fasting serum levels of trimethylamine N-oxide (TMAO) and numerous triglycerides were elevated. Various serum phosphotidylcholine species were decreased. These results demonstrate that nitrite-containing sausages may exaccerbate the development of CRC pathology in APCMin mice to a greater extent than nitrite-free sausages, and this is associated with greater lipid peroxidation, wide-ranging metabolic alternation and gut dysbiosis.

中文翻译:

膳食中包含含亚硝酸盐的法兰克福香肠会加剧 APCmin 小鼠的结直肠癌病理、改变新陈代谢并导致肠道菌群失调

结直肠癌 (CRC) 是欧洲第二大流行的恶性肿瘤,饮食是一个重要的可改变风险因素。食用加工肉类,包括含有亚硝酸钠等防腐盐的肉类,与 CRC 的发病机制有关。本研究调查了食用猪肉 8 周后腺瘤性结肠息肉病 (APC) 多发性肠肿瘤 (min) 小鼠的 CRC 病理学和代谢状态如何受到干扰。将无亚硝酸盐猪肉、无亚硝酸盐香肠或含亚硝酸盐香肠(法兰克福香肠)的膳食内含物 (15%) 与平行对照组 (100% 食物) 进行比较。综合研究调查:胃肠道组织学(肿瘤、异常隐窝病灶 (ACF) 和粘蛋白 deplin 病灶 (MDF)、脂质过氧化(尿液和血清)、粪便微生物群和血清代谢组学(599 种代谢物)。8 周后,食用法兰克福香肠饮食的小鼠胃肠道肿瘤比对照组多 53% (P=0.014),尽管 ACF 和 MDF 没有差异。法兰克福香肠组的尿液和血清脂质过氧化标志物分别高出 59% (P=0.001) 和 108% (P=0.001)。这些小鼠的肠道菌群失调很明显,拟杆菌相对较少,而厚壁菌门较多。三甲胺 N-氧化物 (TMAO) 和许多甘油三酯的空腹血清水平升高。多种血清磷脂酰胆碱种类减少。这些结果表明,与不含亚硝酸盐的香肠相比,含亚硝酸盐的香肠可能会在更大程度上加剧 APCMin 小鼠 CRC 病理学的发展,并且这与更大的脂质过氧化有关,
更新日期:2022-11-26
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