From the Department of Medicine (Neurology) (A.I.M., F.Z., Y.Z., H.T.), The University of British Columbia, Vancouver; National Microbiology Laboratory (N.K., G.V.D., M.G.), Public Health Agency of Canada; Department of Medical Microbiology and Infectious Diseases (N.K., G.V.D., M.G.), Department of Internal Medicine, Max Rady College of Medicine, Rady Faculty of Health Sciences (C.N.B., R.A.M.), and Inflammatory Bowel Disease Clinical and Research Centre (C.N.B.), University of Manitoba, Winnipeg; Roy Romanow Provincial Laboratory (J.D.F.), Regina; Department of Pathology and Laboratory Medicine (J.D.F.), College of Medicine, University of Saskatchewan, Saskatoon, Canada; Department of Neurology (J.H., E.W.), University of California San Francisco; Department of Pediatrics (Neurology) (E.A.Y., J.O.), The Hospital for Sick Children, Toronto; Department of Neurology and Neurosurgery (D.L.A.), Montreal Neurological Institute, McGill University, Montreal, Canada; Centre for Neuroinflammation and Experimental Therapeutics and Department of Neurology (A.B.-O.), University of Pennsylvania Perelman School of Medicine, Philadelphia; Faculty of Health Sciences (W.H.), Simon Fraser University, Burnaby, Canada; and The Children's Hospital of Philadelphia (B.B.), PA.
Neurology. 2022 Mar 8;98(10):e1050-e1063. doi: 10.1212/WNL.0000000000013245. Epub 2021 Dec 22.
Little is known of the functional potential of the gut microbiome in pediatric-onset multiple sclerosis (MS). We performed metagenomic analyses using stool samples from individuals with pediatric-onset MS and unaffected controls.
Persons ≤21 years old enrolled in the Canadian Pediatric Demyelinating Disease Network providing a stool sample were eligible. Twenty patients with MS (McDonald criteria) with symptom onset <18 years were matched to 20 controls by sex, age (±3 years), stool consistency, and race. Microbial taxonomy and functional potentials were estimated from stool sample-derived metagenomic reads and compared by disease status (MS vs controls) and disease-modifying drug (DMD) exposure using alpha diversity, relative abundance, and prevalence using Wilcoxon rank sum, ALDEx2, and Fisher exact tests, respectively.
Individuals with MS were aged 13.6 years (mean) at symptom onset and 8 were DMD-naive. Mean ages at stool sample were 16.1 and 15.4 years for MS and control participants, respectively; 80% were girls. Alpha diversity of enzymes and proteins did not differ by disease or DMD status ( > 0.20), but metabolic pathways, gene annotations, and microbial taxonomy did. Individuals with MS (vs controls) exhibited higher methanogenesis prevalence (odds ratio 10, = 0.044) and abundance (log fold change [LFC] 1.7, = 0.0014), but lower homolactic fermentation abundance (LFC -0.48, = 0.039). Differences by DMD status included lower phosphate butyryl transferase for DMD-naive vs exposed patients with MS (LFC -1.0, = 0.033).
The gut microbiome's functional potential and taxonomy differed between individuals with pediatric-onset MS vs controls, including higher prevalence of a methane-producing pathway from and depletion of the lactate fermentation pathway. DMD exposure was associated with butyrate-producing enzyme enrichment. Together these findings indicate that the gut microbiome of individuals with MS may have a disturbed functional potential.
儿童发病多发性硬化症（MS）患者的肠道微生物组的功能潜能知之甚少。我们使用来自儿童发病 MS 患者和未受影响对照者的粪便样本进行了宏基因组分析。
符合条件的是参加加拿大儿科脱髓鞘疾病网络的≤21 岁个体，他们提供了粪便样本。20 例符合 McDonald 标准的 MS 患者（发病年龄<18 岁）与 20 名性别、年龄（±3 岁）、粪便稠度和种族匹配的对照者进行了匹配。从粪便样本衍生的宏基因组读中估计微生物分类和功能潜能，并通过疾病状态（MS 与对照）和疾病修饰药物（DMD）暴露进行比较，使用 Wilcoxon 秩和检验、ALDEx2 和 Fisher 精确检验分别比较 alpha 多样性、相对丰度和患病率。
MS 患者的症状发病年龄为 13.6 岁（平均），8 例患者为 DMD 初治者。MS 和对照组参与者的粪便样本平均年龄分别为 16.1 岁和 15.4 岁，80%为女孩。酶和蛋白的 alpha 多样性不因疾病或 DMD 状态而不同（>0.20），但代谢途径、基因注释和微生物分类学则不同。与对照组相比，MS 患者的产甲烷作用的患病率更高（优势比 10，=0.044）和丰度更高（对数倍变化[LFC]1.7，=0.0014），但同型乳酸发酵丰度较低（LFC-0.48，=0.039）。DMD 状态的差异包括 DMD 初治者的磷酸盐丁酰转移酶低于 DMD 暴露者（LFC-1.0，=0.033）。
与对照组相比，儿童发病 MS 患者的肠道微生物组的功能潜能和分类学存在差异，包括甲烷生成途径的患病率更高和乳酸发酵途径的丰度降低。DMD 暴露与丁酸盐产生酶的富集有关。总之，这些发现表明 MS 患者的肠道微生物组可能具有功能失调的潜能。
