Immunomodulatory effects of pre- and probiotics

益生菌和益生菌的免疫调节作用

• 批准号: BB/H00470X/1
• 负责人: Parveen Yaqoob
• 金额: $ 69.16万
• 依托单位: University of Reading
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FH00470X%2F1
• 关键词: Immunomodulatory; effects; pre; probiotics

The number of people aged 65 years and over is expected to rise by over 60% in the next 25 years, which presents an enormous challenge for the healthcare system. Elderly people suffer from more frequent and severe infections than younger people; influenza is particularly common in older individuals and is a major cause of death in the elderly population. Ageing dramatically affects immune function; as we age, the repertoire of cells potentially available to respond to a new pathogen shrinks and there is an accumulation of poorly functioning mature cells. This phenomenon is known as immunosenescence and partly explains the increased susceptibility for infection in older individual. Vaccination is recommended to protect the older people against influenza, but immunosenescence also reduces the efficacy of vaccination. It has been estimated that 30-50% of older adults fail to mount protective antibody responses after influenza vaccination, representing a considerable waste of resource and a false sense of security for those receiving the vaccinations. Probiotics are beneficial bacteria, which can be consumed and which have a long and safe record of use in humans. They have shown promise in the prevention or treatment of several disease states ranging from lactose intolerance, constipation and diarrhoea, alleviation of allergy and even to more chronic systemic diseases, such as cardiovascular disease and cancer. Often they are taken together with prebiotics, which are normally fermentable carbohydrates that provide a food source for the beneficial bacteria when they reach the lower gut. There is particular interest in the positive influences of pre- and probiotics in older people, who are subject to alteration in gut microflora composition as well as immunosenescence. Several studies have demonstrated beneficial effects of specific pre- and probiotics on immune function in older subjects. However, none of these studies have taken into account the age-related shift in immune cell populations. Furthermore, there is little understanding of the mechanisms underlying these effects. Despite this, probiotics have recently been proposed as prime candidates for 'anti-immunosenescence' therapy. We propose to investigate the impact of a pre- and probiotic on immune function in young and older subjects, taking into account the age-related shifts in immunity due to immunosenescence. We aim to establish biomarkers and methodology which could be exploited to establish the underpinning science behind the immunomodulatory effects of commercial pre- and probiotics. The project will involve 60 young (18-35y) and 60 older (65-85y) subjects, who will take a pre- and probiotic mixture or a placebo for a total of 8 weeks. The probiotic is not currently commercially produced, but has been demonstrated to have particular ecological fitness and anti-pathogenic effects in the gastrointestinal tract in old age. A suitable prebiotic will be selected on the basis of ability to promote optimal growth and survival of this probiotic. After 4 weeks on the treatment, the subjects will receive an influenza vaccination. Blood samples will be taken before treatment, and at 4, 6 and 8 weeks after commencement. The samples taken at 6 and 8 weeks will be used to assess the immune response to the vaccination. A wide range of immune parameters will be assessed, taking into account the age-related shifts in immune cell populations. In conjunction with the human study, a series of in vitro studies will investigate the mechanistic basis for the impact of the probiotic on immune function and will determine whether there are differential effects of the probiotic in young and older subjects at the cellular and molecular level. The overall aim of both components of the project is to determine whether older subjects derive specific additional benefit from pre- and probiotics by modulation of the impact of immunological ageing.

在未来25年中，65岁及以上的人数预计将增加60％以上，这对医疗保健系统提出了巨大的挑战。老年人比年轻人更频繁和严重感染。流感在老年人中尤其常见，是老年人口的主要死亡原因。衰老会极大地影响免疫功能；随着年龄的增长，细胞的曲目可能可用于应对新的病原体收缩，并且积累了功能较差的成熟细胞。这种现象被称为免疫衰老，部分解释了老年人感染的敏感性增加。建议进行疫苗接种以保护老年人免受流感侵害，但免疫衰老也降低了疫苗接种的疗效。据估计，在流感疫苗接种后，有30-50％的老年人未能实现保护性抗体反应，这代表了接受疫苗接种的人的大量浪费和错误的安全感。益生菌是有益的细菌，可以食用，并且在人类中具有长期安全的使用记录。他们在预防或治疗几种疾病状态方面表现出了希望，从乳糖不耐症，便秘和腹泻，缓解过敏甚至更多慢性全身性疾病（例如心血管疾病和癌症）。通常，它们与益生元一起进行，它们通常是可发酵的碳水化合物，当它们到达较低的肠道时，它们为有益细菌提供了食物来源。对老年人的前和益生菌的积极影响特别感兴趣，这些老年人会受到肠道菌群组成以及免疫衰老的改变。几项研究表明，特定前和益生菌对老年受试者免疫功能的有益作用。但是，这些研究都没有考虑到免疫细胞群体与年龄相关的转移。此外，对这些效果的基础机制几乎没有理解。尽管如此，最近还是提出了益生菌作为“抗免疫”疗法的主要候选者。我们提议研究预先考虑到年龄相关的因免疫衰老引起的与年龄相关的免疫变化，研究益生菌对年轻和老年受试者免疫功能的影响。我们旨在建立生物标志物和方法论，可以利用这些生物标志物和方法来建立商业前和益生菌的免疫调节作用背后的基础科学。该项目将涉及60名年轻（18-35岁）和60名年龄较大（65-85岁）的受试者，他们将服用前和益生菌的混合物或安慰剂，总计8周。目前尚未商业生产益生菌，但已被证明在老年对胃肠道中具有特殊的生态适应性和抗病原作用。将根据促进该益生菌的最佳生长和生存的能力选择合适的益生元。治疗4周后，受试者将接受流感疫苗接种。血液样本将在治疗前，在开始后的4、6和8周。在6和8周时采集的样品将用于评估对疫苗接种的免疫反应。考虑到免疫细胞群体中与年龄相关的变化，将评估广泛的免疫参数。结合人类研究，一系列体外研究将研究益生菌对免疫功能的影响的机理基础，并将确定益生菌在细胞和分子水平上是否存在益生菌的差异作用。该项目的两个组成部分的总体目的是确定较老的受试者是否通过调节免疫老化的影响来从预生物和益生菌中获得特定的额外好处。

项目成果

Additional file 1: Figure S1. of Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence

附加文件 1：图 S1。

• DOI: 10.6084/m9.figshare.c.3599351_d3
• 发表时间: 2016
• 作者: Przemska-Kosicka A

Impact of ageing and a synbiotic on the immune response to seasonal influenza vaccination; a randomised controlled trial.

• DOI: 10.1016/j.clnu.2017.01.011
• 发表时间: 2018-04
• 期刊: Clinical nutrition (Edinburgh, Scotland)
• 作者: Enani S;Przemska-Kosicka A;Childs CE;Maidens C;Dong H;Conterno L;Tuohy K;Todd S;Gosney M;Yaqoob P
• 通讯作者: Yaqoob P

Impact of probiotics on the immune response to influenza vaccination is strongly influenced by ageing

益生菌对流感疫苗免疫反应的影响受到衰老的强烈影响

• DOI: 10.1111/nbu.12253
• 发表时间: 2017
• 期刊: Nutrition Bulletin
• 影响因子: 3.3
• 作者: Yaqoob P

Additional file 3: Figure S3. of Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence

附加文件 3：图 S3。

• DOI: 10.6084/m9.figshare.c.3599351_d2
• 发表时间: 2016
• 作者: Przemska-Kosicka A

Effect of a synbiotic on the response to seasonal influenza vaccination is strongly influenced by degree of immunosenescence.

• DOI: 10.1186/s12979-016-0061-4
• 发表时间: 2016
• 期刊: Immunity & ageing : I & A
• 作者: Przemska-Kosicka A;Childs CE;Enani S;Maidens C;Dong H;Dayel IB;Tuohy K;Todd S;Gosney MA;Yaqoob P
• 通讯作者: Yaqoob P