儿童多发性硬化症和脱髓鞘综合征中的肠道微生物群。
The gut microbiota in pediatric multiple sclerosis and demyelinating syndromes.
机构信息
Medicine (Neurology), University of British Columbia and The Djavad Mowafaghian Centre for Brain Health, Vancouver, BC, V6T 1Z3, Canada.
The Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
出版信息
Ann Clin Transl Neurol. 2021 Dec;8(12):2252-2269. doi: 10.1002/acn3.51476. Epub 2021 Dec 9.
OBJECTIVE
To examine the gut microbiota in individuals with and without pediatric-onset multiple sclerosis (MS).
METHODS
We compared stool-derived microbiota of Canadian Pediatric Demyelinating Disease Network study participants ≤21 years old, with MS (disease-modifying drug [DMD] exposed and naïve) or monophasic acquired demyelinating syndrome [monoADS] (symptom onset <18 years), and unaffected controls. All were ≥30 days without antibiotics or corticosteroids. V4 region 16S RNA gene-derived amplicon sequence variants (Illumina MiSeq) were assessed using negative binomial regression and network analyses; rate ratios were age- and sex-adjusted (aRR).
RESULTS
Thirty-two MS, 41 monoADS (symptom onset [mean] = 14.0 and 6.9 years) and 36 control participants were included; 75%/56%/58% were female, with mean ages at stool sample = 16.5/13.8/15.1 years, respectively. Nine MS cases (28%) were DMD-naïve. Although microbiota diversity (alpha, beta) did not differ between participants (p > 0.1), taxa-level and gut community networks did. MS (vs. monoADS) exhibited > fourfold higher relative abundance of the superphylum Patescibacteria (aRR = 4.2;95%CI:1.6-11.2, p = 0.004, Q = 0.01), and lower abundances of short-chain fatty acid (SCFA)-producing Lachnospiraceae (Anaerosporobacter) and Ruminococcaceae (p, Q < 0.05). DMD-naïve MS cases were depleted for Clostridiales vadin-BB60 (unnamed species) versus either DMD-exposed, controls (p, Q < 0.01), or monoADS (p = 0.001, Q = 0.06) and exhibited altered community connectedness (p < 10 Kruskal-Wallis), with SCFA-producing taxa underrepresented. Consistent taxa-level findings from an independent US Network of Pediatric MS Centers case/control (n = 51/42) cohort included >eightfold higher abundance for Candidatus Stoquefichus and Tyzzerella (aRR = 8.8-12.8, p < 0.05) in MS cases and 72%-80% lower abundance of SCFA-producing Ruminococcaceae-NK4A214 (aRR = 0.38-0.2, p ≤ 0.01).
INTERPRETATION
Gut microbiota community structure, function and connectivity, and not just individual taxa, are of likely importance in MS.
目的
研究儿科发病多发性硬化症（MS）患者与非 MS 患者的肠道微生物群。
方法
我们比较了加拿大儿科脱髓鞘疾病网络研究参与者的粪便衍生微生物群，这些参与者年龄均≤21 岁，患有 MS（接受疾病修正治疗 [DMD] 和未接受 DMD）或单相获得性脱髓鞘综合征 [monoADS]（症状发作<18 岁），以及无影响的对照组。所有参与者均在≥30 天内未使用抗生素或皮质类固醇。使用负二项式回归和网络分析评估 V4 区 16S RNA 基因衍生扩增子序列变异（Illumina MiSeq）；年龄和性别调整后的率比（aRR）。
结果
32 例 MS、41 例 monoADS（症状发作[平均值]=14.0 和 6.9 岁）和 36 例对照组参与者被纳入研究；75%/56%/58%为女性，粪便样本的平均年龄分别为 16.5/13.8/15.1 岁。9 例 MS 患者（28%）未接受 DMD 治疗。尽管参与者之间的微生物多样性（alpha，beta）没有差异（p>0.1），但分类群水平和肠道群落网络存在差异。MS（与 monoADS 相比）表现出超门 Patescibacteria 的相对丰度高出四倍以上（aRR=4.2；95%CI：1.6-11.2，p=0.004，Q=0.01），短链脂肪酸（SCFA）产生的 Lachnospiraceae（Anaerosporobacter）和 Ruminococcaceae 的丰度较低（p，Q<0.05）。未接受 DMD 治疗的 MS 病例中，Clostridiales vadin-BB60（未命名物种）的丰度低于接受 DMD 治疗的病例、对照组（p，Q<0.01）或 monoADS（p=0.001，Q=0.06），且表现出改变的群落连通性（p<10 克朗瓦尔-沃利斯），代表性的 SCFA 产生分类群不足。来自美国儿科多发性硬化症中心病例对照网络（n=51/42）的独立队列的一致分类群水平发现包括 Candidatus Stoquefichus 和 Tyzzerella 的丰度高出八倍以上（aRR=8.8-12.8，p<0.05），以及 SCFA 产生的 Ruminococcaceae-NK4A214 的丰度低 72%-80%（aRR=0.38-0.2，p≤0.01）。
解释
肠道微生物群落结构、功能和连通性，而不仅仅是单个分类群，在 MS 中可能很重要。
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