Duscha Alexander, Hegelmaier Tobias, Dürholz Kerstin, Desel Christiane, Gold Ralf, Zaiss Mario M, Haghikia Aiden
Department of Neurology, Universitätsklinikum Magdeburg A.ö.R., Otto von Guericke University Magdeburg, Magdeburg, Germany.
Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-University Erlangen-Nürnberg (FAU) and Universitätsklinik Erlangen, Erlangen, Germany.
Ther Adv Neurol Disord. 2022 Jun 21;15:17562864221103935. doi: 10.1177/17562864221103935. eCollection 2022.
The impact of the gut and its microbiota are increasingly appreciated in health and disease. Short-chain fatty acids (SCFAs) are among the main metabolites synthesized from bacterial fermentation. Recently, we showed the anti-inflammatory and potentially neuroprotective effect of propionic acid (PA) in multiple sclerosis (MS). Osteoporosis is one of the most common co-morbidities for MS patients with limited therapeutic options available. Osteoporosis is closely linked to an imbalance of cells of the immune system and an immune-mediated impact on bone structure the gut has been shown. Interestingly, intake of SCFA leads to bone mass increase and concomitant reduction of inflammation-induced bone loss in mice.
To determine the impact of PA supplementation on markers of bone metabolism in MS patients.
We investigated the influence of 14 days supplementation with PA on bone metabolism in 20 MS patients. To this end, β-CrossLaps and osteocalcin, established markers of bone metabolism, were measured in serum before and after PA intake and correlated with phenotypic and functional immunodata.
Supplementation with PA induced a significant increase in serum levels of osteocalcin, a surrogate marker for bone formation. Levels of β-CrossLaps, a marker for bone resorption, were significantly decreased after therapy. Regulatory T-cell (Treg) numbers and suppressive capacity positively correlated with serum levels of osteocalcin while Th17 cell numbers showed an inverse correlation. Our findings are in line with animal studies showing that SCFA induced increased bone formation and reduced bone resorption.
In addition to its immune regulatory, disease-modifying effect on MS disease course, supplementation with PA beneficially influences serum levels of β-CrossLaps and osteocalcin and may thus also protect against osteoporosis, a common co-morbidity in MS.
肠道及其微生物群在健康和疾病中的影响日益受到重视。短链脂肪酸（SCFAs）是细菌发酵产生的主要代谢产物之一。最近，我们发现丙酸（PA）在多发性硬化症（MS）中具有抗炎和潜在的神经保护作用。骨质疏松症是MS患者最常见的合并症之一，可用的治疗选择有限。骨质疏松症与免疫系统细胞失衡以及对骨骼结构的免疫介导影响密切相关，而肠道已被证明与之有关。有趣的是，摄入SCFA可导致小鼠骨量增加，并同时减少炎症诱导的骨质流失。
确定补充PA对MS患者骨代谢标志物的影响。
我们研究了20例MS患者补充PA 14天对骨代谢的影响。为此，在摄入PA前后测量血清中已确立的骨代谢标志物β-交联C端肽和骨钙素，并将其与表型和功能性免疫数据相关联。
补充PA可导致血清骨钙素水平显著升高，骨钙素是骨形成的替代标志物。治疗后，骨吸收标志物β-交联C端肽水平显著降低。调节性T细胞（Treg）数量和抑制能力与血清骨钙素水平呈正相关，而Th17细胞数量呈负相关。我们的发现与动物研究一致，表明SCFA可诱导骨形成增加和骨吸收减少。
除了对MS病程具有免疫调节、疾病修饰作用外，补充PA还对血清β-交联C端肽和骨钙素水平产生有益影响，因此也可能预防骨质疏松症，这是MS中常见的合并症。
