Bruijstens Arlette L, Molenaar Sandy, Wong Yu Yi M, Kraaij Robert, Neuteboom Rinze F
Department of Neurology, Erasmus University Medical Center, Rotterdam, the Netherlands.
Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands.
Eur J Neurol. 2023 Nov;30(11):3507-3515. doi: 10.1111/ene.15594. Epub 2022 Oct 27.
Gut microbiota dysbiosis may lead to proinflammatory conditions contributing to multiple sclerosis (MS) etiology. Pediatric-onset MS patients are close to biological disease onset and less exposed to confounders. Therefore, this study investigated gut microbiota composition and functional pathways in pediatric-onset MS, compared to monophasic acquired demyelinating syndromes (mADS) and healthy controls (HCs).
Pediatric participants were selected from the Dutch national prospective cohort study including ADS patients and HCs <18 years old. Amplicon sequence variants (ASVs) were generated from sequencing the V3/4 regions of the 16S rRNA gene. Functional MetaCyc microbial pathways were predicted based on Enzyme Commission numbers. Gut microbiota composition (alpha/beta diversity and individual microbe abundance at ASV to phylum level) and predicted functional pathways were tested using nonparametric tests, permutational multivariate analysis of variance, and linear regression.
Twenty-six pediatric-onset MS (24 with disease-modifying therapy [DMT]), 25 mADS, and 24 HC subjects were included. Alpha/beta diversity, abundance of individual resident microbes, and microbial functional features were not different between these participant groups. Body mass index (BMI) showed significant differences, with obese children having a lower alpha diversity (Chao1 Index p = 0.015, Shannon/Simpson Diversity Index p = 0.014/p = 0.023), divergent beta diversity (R = 3.7%, p = 0.013), and higher abundance of numerous individual resident microbes and functional microbial pathways.
Previous results of gut microbiota composition and predicted functional features could not be validated in this Dutch pediatric-onset MS cohort using a more sensitive 16S pipeline, although it was limited by sample size and DMT use. Notably, several other host-related factors were found to associate with gut microbiota variation, especially BMI.
肠道微生物群失调可能导致促炎状态，这在多发性硬化症（MS）的病因中起作用。儿童期发病的MS患者接近疾病生物学发病期，且较少受到混杂因素影响。因此，本研究调查了儿童期发病的MS患者的肠道微生物群组成和功能途径，并与单相获得性脱髓鞘综合征（mADS）和健康对照（HC）进行比较。
从荷兰全国前瞻性队列研究中选取18岁以下的ADS患者和HC作为儿科参与者。通过对16S rRNA基因的V3/4区域进行测序生成扩增子序列变体（ASV）。基于酶委员会编号预测功能性MetaCyc微生物途径。使用非参数检验、置换多元方差分析和线性回归对肠道微生物群组成（α/β多样性以及从ASV到门水平的个体微生物丰度）和预测的功能途径进行测试。
纳入了26例儿童期发病的MS患者（24例接受疾病修饰治疗[DMT]）、25例mADS患者和24例HC受试者。这些参与者组之间的α/β多样性、个体常驻微生物丰度和微生物功能特征没有差异。体重指数（BMI）显示出显著差异，肥胖儿童的α多样性较低（Chao1指数p = 0.015，香农/辛普森多样性指数p = 0.014/p = 0.023），β多样性存在差异（R = 3.7%，p = 0.013），并且许多个体常驻微生物和功能性微生物途径的丰度更高。
尽管本研究受样本量和DMT使用的限制，但使用更灵敏的16S流程，在这个荷兰儿童期发病的MS队列中未能验证先前关于肠道微生物群组成和预测功能特征的结果。值得注意的是，发现其他几个与宿主相关的因素与肠道微生物群变异有关，尤其是BMI。
