Ann Romney Center for Neurologic Diseases, Partners Multiple Sclerosis Center, Brigham and Women's Hospital, Department of Neurology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Evergrande Center for Immunologic Diseases.
Ann Neurol. 2018 Jun;83(6):1147-1161. doi: 10.1002/ana.25244. Epub 2018 Jun 8.
Effect of a probiotic on the gut microbiome and peripheral immune function in healthy controls and relapsing-remitting multiple sclerosis (MS) patients.
MS patients (N = 9) and controls (N = 13) were orally administered a probiotic containing Lactobacillus, Bifidobacterium, and Streptococcus twice-daily for two months. Blood and stool specimens were collected at baseline, after completion of the 2-month treatment, and 3 months after discontinuation of therapy. Frozen peripheral blood mononuclear cells (PBMCs) were used for immune cell profiling. Stool samples were used for 16S rRNA profiling and metabolomics.
Probiotic administration increased the abundance of several taxa known to be depleted in MS such as Lactobacillus. We found that probiotic use decreased the abundance of taxa previously associated with dysbiosis in MS, including Akkermansia and Blautia. Predictive metagenomic analysis revealed a decrease in the abundance of several KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways associated with altered gut microbiota function in MS patients, such as methane metabolism, following probiotic supplementation. At the immune level, probiotic administration induced an anti-inflammatory peripheral immune response characterized by decreased frequency of inflammatory monocytes, decreased mean fluorescence intensity (MFI) of CD80 on classical monocytes, as well as decreased human leukocyte antigen (HLA) D related MFI on dendritic cells. Probiotic administration was also associated with decreased expression of MS risk allele HLA-DQA1 in controls. Probiotic-induced increase in abundance of Lactobacillus and Bifidobacterium was associated with decreased expression of MS risk allele HLA.DPB1 in controls.
Our results suggest that probiotics could have a synergistic effect with current MS therapies. Ann Neurol 2018.
研究益生菌对健康对照者和复发性缓解型多发性硬化症(MS)患者肠道微生物组和外周免疫功能的影响。
将 MS 患者(N=9)和对照者(N=13)分为两组,分别口服含有乳杆菌、双歧杆菌和链球菌的益生菌,每天两次,持续两个月。在基线、治疗结束后两个月和停药 3 个月时采集血样和粪便标本。使用冷冻的外周血单核细胞(PBMCs)进行免疫细胞分析。使用粪便样本进行 16S rRNA 分析和代谢组学分析。
益生菌的使用增加了一些在 MS 中丰度降低的菌群,如乳杆菌。我们发现,益生菌的使用降低了与 MS 中菌群失调相关的菌群丰度,包括阿克曼氏菌和布劳特氏菌。预测代谢组学分析显示,益生菌补充后,与 MS 患者肠道微生物群功能改变相关的几个 KEGG(京都基因与基因组百科全书)途径的丰度降低,如甲烷代谢。在免疫水平上,益生菌的使用诱导了一种抗炎的外周免疫反应,表现为炎症性单核细胞频率降低,经典单核细胞上 CD80 的平均荧光强度(MFI)降低,树突状细胞上 HLA 相关 MFI 降低。益生菌的使用还与对照组 HLA-DQA1 风险等位基因表达降低有关。益生菌诱导的乳杆菌和双歧杆菌丰度增加与对照组 HLA-DPB1 风险等位基因表达降低有关。
我们的研究结果表明,益生菌可能与目前的 MS 治疗方法具有协同作用。神经病学年鉴 2018 年。