Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.
Early life exposure to broccoli sprouts confers stronger protection against enterocolitis development in an immunological mouse model of inflammatory bowel disease.
复制标题
在炎症性肠病的免疫小鼠模型中，生命早期接触西兰花芽可以提供更强的保护，防止小肠结肠炎的发展。
DOI：
10.1101/2023.01.27.525953
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Ishaq,Suzanne
中科院分区：
文献类型：
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作者：
Holcomb,Lola;Holman,JohannaM;Hurd,Molly;Lavoie,Brigitte;Colucci,Louisa;Hunt,Benjamin;Hunt,Timothy;Kinney,Marissa;Pathak,Jahnavi;Mawe,GaryM;Moses,PeterL;Perry,Emma;Stratigakis,Allesandra;Zhang,Tao;Chen,Grace;Ishaq,Suzanne
克罗恩病（CD）是一种炎症性肠病（IBD）的表现，在儿童和青少年中表现出来，涉及慢性和严重的小肠结肠炎，免疫和肠道微生物失调以及其他并发症。饮食和肠道微生物群产生的代谢产物是可以改善症状的抗炎药的来源。然而，关于IBD如何影响肠道中微生物位置和功能的肠道微生物学模式，早期生活过渡肠道群落如何受到IBD和饮食干预的影响，以及肠道微生物学的破坏如何改变饮食成分或微生物代谢产物的疾病介导，仍然存在问题。尽管存在免疫调节的CD模型，但许多关于饮食和IBD的研究仍使用化学诱导的溃疡性结肠炎模型。在C57 BL/6背景下的白细胞介素-10-敲除（IL-10-KO）小鼠，从4或7周龄开始，喂食对照饮食或含有10%（wt/wt）生西兰花芽的饮食，其在芽来源的抗炎萝卜硫素中含量高。在接种肝螺杆菌前7天和接种后2周开始饮食，肝螺杆菌在这些免疫受损的小鼠中引发克罗恩病样症状。西兰花芽饮食增加了血浆中的萝卜硫素;减少了体重停滞，粪便血液和相关腹泻;增加了肠道中的微生物群丰富度，特别是在年轻小鼠中。低热量饮食导致年轻小鼠体内产生一些解剖学上特异性的细菌，并减少了IL-10-KO小鼠体内引发炎症的致病菌的流行和丰度，例如大肠杆菌和螺杆菌。总的来说，IL-10-KO小鼠模型对生西兰花芽饮食有反应，并代表了更多饮食-宿主-微生物组研究的机会。重要信息据我们所知，IL-10-KO小鼠以前没有被用于研究宿主，微生物群和西兰花，西兰花芽或西兰花生物活性物质在解决CD症状中的相互作用。我们发现，含有10%生西兰花芽的饮食增加了抗炎化合物萝卜硫素的血浆浓度，并在不同程度上保护小鼠免受疾病症状，包括体重减轻或停滞，粪便血液和腹泻。年轻小鼠对饮食的反应更强烈，进一步减轻症状，以及肠道细菌丰富度增加，细菌群落彼此相似性增加，并且比饮食干预的老年小鼠具有更多的位置特异性群落。克罗恩病扰乱了患者的生活，需要人们改变饮食和生活习惯来控制症状。目前的医疗费用昂贵，副作用明显，饮食干预是一种负担得起的，可获得的，简单的策略，以减少症状的负担。
Crohn’s disease (CD) is a presentation of inflammatory bowel disease (IBD) that manifests in childhood and adolescence and involves chronic and severe enterocolitis, immune and gut microbial dysregulation, and other complications. Diet and gut-microbiota-produced metabolites are sources of anti-inflammatories that could ameliorate symptoms. However, questions remain on how IBD influences biogeographic patterns of microbial location and function in the gut, how early life transitional gut communities are affected by IBD and diet interventions, and how disruption to biogeography alters disease mediation by diet components or microbial metabolites. Many studies on diet and IBD use a chemically induced ulcerative colitis model, despite the availability of an immune-modulated CD model. Interleukin-10-knockout (IL-10-KO) mice on a C57BL/6 background, beginning at age 4 or 7 weeks, were fed a control diet or one containing 10% (wt/wt) raw broccoli sprouts, which was high in the sprout-sourced anti-inflammatory sulforaphane. Diets began 7 days prior to, and for 2 weeks after inoculation withHelicobacter hepaticus,which triggers Crohn’s-like symptoms in these immune-impaired mice. The broccoli sprout diet increased sulforaphane in plasma; decreased weight stagnation, fecal blood, and diarrhea associated; and increased microbiota richness in the gut, especially in younger mice. Sprout diets resulted in some anatomically specific bacteria in younger mice and reduced the prevalence and abundance of pathobiont bacteria which trigger inflammation in the IL-10-KO mouse, for example,Escherichia coliandHelicobacter. Overall, the IL-10-KO mouse model is responsive to a raw broccoli sprout diet and represents an opportunity for more diet-host-microbiome research.IMPORTANCETo our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention. Crohn’s disease disrupts the lives of patients and requires people to alter dietary and lifestyle habits to manage symptoms. The current medical treatment is expensive with significant side effects, and a dietary intervention represents an affordable, accessible, and simple strategy to reduce the burden of symptoms.