Lurz Eberhard, Horne Rachael G, Määttänen Pekka, Wu Richard Y, Botts Steven R, Li Bo, Rossi Laura, Johnson-Henry Kathene C, Pierro Agostino, Surette Michael G, Sherman Philip M
Cell Biology Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.
Division of Gastroenterology, Hepatology and Nutrition, Department of Paediatrics, Toronto, ON, Canada.
Front Nutr. 2020 Jun 5;7:83. doi: 10.3389/fnut.2020.00083. eCollection 2020.
Inflammatory bowel disease (IBD) refers to a spectrum of autoimmune diseases, which result in chronic intestinal inflammation. Previous findings suggest a role for diet, nutrition and dysbiosis of the gut microbiota in both the development and progression of the condition. Vitamin B12 is a key cofactor of methionine synthase and is produced solely by microbes. Previous work links increased levels of homocysteine, a substrate of methionine synthase, MetH, to IBD indicating a potential role for vitamin B12 deficiency in intestinal injury and inflammation. This study assessed the role of vitamin B12 in shaping the gut microbiota and determining responses to intestinal injury using a reproducible murine model of colitis. The effects of vitamin B12 supplementation and deficiency were assessed ; 3-week-old post-weanling C57Bl/6 mice were divided into three dietary treatment groups: (1) sufficient vitamin B12 (50 mg/Kg), (2) deficient vitamin B12 (0 mg/Kg) and (3) supplemented vitamin B12 (200 mg/Kg) for a period of 4 weeks. Intestinal injury was induced with 2% dextran sodium sulphate (DSS) via drinking water for 5 days. The impact of varying levels of dietary vitamin B12 on gut microbiota composition was assessed using 16S rRNA gene sequencing from fecal samples collected at day 0 and day 28 of the dietary intervention, and 7 days following induction of colitis on day 38, when blood and colonic tissues were also collected. No significant alterations were found in the gut microbiota composition of disease-free animals in response to dietary interventions. By contrast, after DSS-induced colitis, >30 genera were significantly altered in vitamin B12 deficient mice. Altered B12 levels produced no significant effect on composite disease-activity scores; however, administration of a B12 deficient diet resulted in reduced DSS-induced epithelial tissue damage. Vitamin B12 supplementation does not alter the gut microbiota composition under healthy conditions, but does contribute to differential microbial responses and intestinal dysbiosis following the induction of experimental colitis.
炎症性肠病（IBD）是指一系列自身免疫性疾病，可导致慢性肠道炎症。先前的研究结果表明，饮食、营养和肠道微生物群失调在该疾病的发生和发展中都起作用。维生素B12是甲硫氨酸合酶的关键辅因子，且仅由微生物产生。先前的研究将甲硫氨酸合酶（MetH）的底物同型半胱氨酸水平升高与IBD联系起来，表明维生素B12缺乏在肠道损伤和炎症中可能起作用。本研究使用可重复的小鼠结肠炎模型评估了维生素B12在塑造肠道微生物群以及确定对肠道损伤的反应中的作用。评估了补充和缺乏维生素B12的影响；将3周龄断奶后的C57Bl/6小鼠分为三个饮食治疗组：（1）维生素B12充足（50 mg/Kg），（2）维生素B12缺乏（0 mg/Kg），（3）补充维生素B12（200 mg/Kg），为期4周。通过饮用水给予2%葡聚糖硫酸钠（DSS）诱导肠道损伤5天。使用16S rRNA基因测序评估不同水平的饮食维生素B12对肠道微生物群组成的影响，测序样本为在饮食干预第0天和第28天以及结肠炎诱导后第38天（此时还采集了血液和结肠组织）收集的粪便样本。未发现无疾病动物的肠道微生物群组成因饮食干预而发生显著改变。相比之下，在DSS诱导的结肠炎后，维生素B12缺乏的小鼠中有超过30个属发生了显著改变。B12水平的改变对综合疾病活动评分没有显著影响；然而，给予缺乏B12的饮食会导致DSS诱导的上皮组织损伤减轻。在健康条件下，补充维生素B12不会改变肠道微生物群组成，但在实验性结肠炎诱导后确实会导致不同的微生物反应和肠道生态失调。
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