饮食对多发性硬化症病程有影响 Diet has an impact on the multiple sclerosis disease course

News Release 11-Mar-2020

Neurology

Ruhr-University Bochum

The short-chain fatty acid propionic acid influences the intestine-mediated immune regulation in people with multiple sclerosis (MS). This has been shown by a team from the Department of Neurology of Ruhr-Universität Bochum (RUB) at St. Josef-Hospital in an international study headed by Professor Aiden Haghikia. The application of propionic acid in addition to MS medication reduced the relapse rate and the risk of disability progression in the long term. Moreover, initial Magnetic Resonance Imaging studies indicated that propionic acid may reduce brain atrophy as a sign of neuronal cell death. The results were published in the journal Cell from 10 March 2020.

Self-sufficient organ within the gut

The gut microbiome, i.e. the entire bacterial colonisation of the intestine, plays an important role not only for the healthy organism, but its association with chronic diseases, such as multiple sclerosis has been recently appreciated. Within the gut, the interaction between dietary components, microbiota, their metabolites, and the immune system takes place in the intestinal wall. “This is how intestinal bacteria can directly and indirectly affect anatomically distant structures such as the brain,” explains Aiden Haghikia. “Accordingly, the gut microbiome acts like an self-sufficient endocrine organ that interacts with the environment.”

Short chain fatty acids can suppress inflammatory reactions

In the current study, the researchers successfully transferred the results previously shown in the cell culture dish and the experimental model to their MS patients: short-chain fatty acids such as propionic acid or its salt propionate increased the differentiation and function of regulatory T cells in the gut. “These cells stop excessive inflammatory processes and reduce auto-immune cells in autoimmune diseases like MS,” says Professor Ralf Gold, Director of the Department of Neurology at St. Josef Hospital.

In their study, the researchers showed that the microbiome composition is altered in MS patients. Moreover, they demonstrated a deficiency of propionic acid in the feces and serum of MS patients, which was most pronounced in the earliest phases of the disease. These data were obtained in collaboration with the Max Delbrück Center Berlin and the Institute of Nutritional Sciences at Martin Luther University Halle-Wittenberg.

Intestinal bacteria and the power plants of the cells of paramount importance

In collaboration with researchers from the Bar-Ilan University in Israel, who had developed an intestinal model for the functional analysis of the microbiome, it emerged that propionate associated changes of the gut microbiome play a crucial role in the differentiation of regulatory cells. The increased function of these cells was due to their improved energy utilisation through an altered function of the mitochondria, as the research team demonstrated in collaboration with the Molecular Cell Biology research group at the RUB Faculty of Medicine.

The intestine as target for future therapeutic approaches

The short-chain fatty acids represent only a fraction of the metabolites of intestinal bacteria that are generated from the diet. “Further research into this largely unknown organ and the knowledge gained from it will enable us to develop innovative dietary measures to complement the known therapeutics in the future,” says Aiden Haghikia.

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Cooperation partners

The study was conducted in collaboration with research teams at the universities of Berlin (Max Delbrück Center), Düsseldorf (Proteomics), Erlangen (Rheumatology), Freiburg (Neuropathology), Halle-Wittenberg (Nutritional Science), Hattingen (Neurology and Complementary Medicine), Copenhagen (Denmark), Leipzig, Los Angeles (USA), Ramat Gan (Israel) and Regensburg (Neurology).

Funding

The research was co-funded by the German Research Foundation as part of the Collaborative Research Centre/Transregio 128 and the Collaborative Research Centre 1365, the RUB Faculty of Medicine in the Forum Programme, Rose-Stiftung, the RUB Centre for Protein Diagnostics Prodi, Deutsche Multiple-Sklerose-Gesellschaft in NRW, the Ministry of Culture and Science in North Rhine-Westphalia (INST 213/840-1 FUGG), the Israel Science Foundation (1384/18) as well as the Federal Ministry of Education and Research (FKZ 031 A 534A).

Original publication

Alexander Duscha, Aiden Haghikia et al.: Propionic acid shapes multiple sclerosis disease course by immunomodulatory mechanism, in: Cell, 2020, DOI: 10.1016/j.cell.2020.02.035, https://www.sciencedirect.com/science/article/pii/S0092867420302129?via%3Dihub

Press contact

Prof. Dr. Aiden Haghikia St. Josef-Hospital Bochum Neurologic Clinic at Ruhr-Universität Bochum Germany Phone: +49 234 509 2422 Email: [email protected]

短链脂肪酸丙酸影响多发性硬化症（MS）患者肠道介导的免疫调节。来自圣约瑟夫医院的波鸿鲁尔大学神经病学系（RUB）的一个团队在艾登·哈吉基亚（Aiden Haghikia）教授的领导下进行的一项国际研究中已经证明了这一点。从长远来看，除了MS药物外，丙酸的使用还降低了复发率和残疾发展的风险。此外，最初的磁共振成像研究表明丙酸可以减少脑萎缩，这是神经元细胞死亡的迹象。该结果于2020年3月10日发表在《细胞》杂志上。

肠道内的自给器官

肠道微生物组，即肠道的整个细菌定植，不仅对健康的生物体起着重要的作用，而且它与诸如多发性硬化症之类的慢性疾病的联系最近也得到了人们的认可。在肠道内，饮食成分，微生物群，其代谢产物和免疫系统之间的相互作用发生在肠壁中。 “这就是肠道细菌可以直接和间接影响解剖学上遥远的结构（例如大脑）的方式，” Aiden Haghikia解释说。 “因此，肠道微生物组的作用就像与环境相互作用的自给自足的内分泌器官。”

短链脂肪酸可以抑制炎症反应

在当前的研究中，研究人员成功地将先前在细胞培养皿和实验模型中显示的结果转移给了他们的MS患者：短链脂肪酸（如丙酸或其丙酸盐）增加了调节性T细胞的分化和功能。肠子。 “这些细胞可以阻止过度的炎症过程，并减少像MS这样的自身免疫性疾病中的自身免疫细胞，”圣约瑟夫医院神经科主任Ralf Gold教授说。

在他们的研究中，研究人员表明，MS患者的微生物组组成发生了改变。而且，他们证明了MS患者粪便和血清中丙酸的缺乏，这在疾病的最早阶段最为明显。这些数据是与柏林马克斯·德尔布吕克中心和马丁·路德大学哈勒·威登堡大学营养科学研究所合作获得的。

肠道细菌和细胞至关重要的发电厂

与以色列Bar-Ilan大学的研究人员合作，他们开发了用于微生物组功能分析的肠道模型，结果表明，肠道微生物组的丙酸相关变化在调节细胞的分化中起着至关重要的作用。这些细胞功能增强是由于线粒体功能改变，从而提高了能量利用率，研究团队与RUB医学院的分子细胞生物学研究小组合作证明了这一点。

肠作为未来治疗方法的目标

短链脂肪酸仅占饮食中肠道细菌代谢产物的一小部分。艾登·哈吉基亚（Aiden Haghikia）表示：“对该未知器官的进一步研究和从中获得的知识将使我们能够开发创新的饮食措施，以补充未来已知的疗法。”

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