Telethon Kids Institute, University of Western Australia, PO Box 855, West Perth, WA, 6872, Australia.
Centre for Neuromuscular and Neurological Disorders, Perron Institute for Neurological and Translational Science, University of Western Australia, Perth, WA, Australia.
Sci Rep. 2021 Mar 4;11(1):5244. doi: 10.1038/s41598-021-84881-8.
Altered composition of gut bacteria and changes to the production of their bioactive metabolites, the short-chain fatty acids (SCFAs), have been implicated in the development of multiple sclerosis (MS). However, the immunomodulatory actions of SCFAs and intermediaries in their ability to influence MS pathogenesis are uncertain. In this study, levels of serum SCFAs were correlated with immune cell abundance and phenotype as well as with other relevant serum factors in blood samples taken at first presentation of Clinically Isolated Syndrome (CIS; an early form of MS) or MS and compared to healthy controls. There was a small but significant reduction in propionate levels in the serum of patients with CIS or MS compared with healthy controls. The frequencies of circulating T follicular regulatory cells and T follicular helper cells were significantly positively correlated with serum levels of propionate. Levels of butyrate associated positively with frequencies of IL-10-producing B-cells and negatively with frequencies of class-switched memory B-cells. TNF production by polyclonally-activated B-cells correlated negatively with acetate levels. Levels of serum SCFAs associated with changes in circulating immune cells and biomarkers implicated in the development of MS.
肠道细菌组成的改变和其生物活性代谢产物短链脂肪酸（SCFAs）的产生变化，与多发性硬化症（MS）的发展有关。然而，SCFAs 的免疫调节作用及其影响 MS 发病机制的能力的中间产物尚不确定。在这项研究中，在首次出现临床孤立综合征（CIS；MS 的早期形式）或 MS 时采集的血液样本中，将血清 SCFA 水平与免疫细胞丰度和表型以及其他相关血清因素相关联，并与健康对照组进行比较。与健康对照组相比，CIS 或 MS 患者的血清中丙酸盐水平略有但显著降低。循环滤泡辅助 T 细胞和滤泡辅助 T 细胞的频率与丙酸盐的血清水平呈显著正相关。丁酸盐水平与产生 IL-10 的 B 细胞的频率呈正相关，与类别转换的记忆 B 细胞的频率呈负相关。多克隆激活的 B 细胞产生的 TNF 与醋酸盐水平呈负相关。血清 SCFA 水平与循环免疫细胞的变化以及与 MS 发展有关的生物标志物相关。
