Division of Epidemiology, University of California, Berkeley, Berkeley, California, USA.
Department of Medicine- Gastroenterology, University of California, San Francisco, San Francisco, California, USA.
Ann Clin Transl Neurol. 2021 Sep;8(9):1867-1883. doi: 10.1002/acn3.51441. Epub 2021 Aug 19.
To identify features of the gut microbiome associated with multiple sclerosis activity over time.
We used 16S ribosomal RNA sequencing from stool of 55 recently diagnosed pediatric-onset multiple sclerosis patients. Microbiome features included the abundance of individual microbes and networks identified from weighted genetic correlation network analyses. Prentice-Williams-Peterson Cox proportional hazards models estimated the associations between features and three disease activity outcomes: clinical relapses and both new/enlarging T2 lesions and new gadolinium-enhancing lesions on brain MRI. Analyses were adjusted for age, sex, and disease-modifying therapies.
Participants were followed, on average, 2.1 years. Five microbes were nominally associated with all three disease activity outcomes after multiple testing correction. These included butyrate producers Odoribacter (relapse hazard ratio = 0.46, 95% confidence interval: 0.24, 0.88) and Butyricicoccus (relapse hazard ratio = 0.49, 95% confidence interval: 0.28, 0.88). Two networks of co-occurring gut microbes were significantly associated with a higher hazard of both MRI outcomes (gadolinium-enhancing lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.29 (1.08, 1.54) and 1.42 (1.18, 1.71), respectively; T2 lesion hazard ratios (95% confidence intervals) for Modules 32 and 33 were 1.34 (1.15, 1.56) and 1.41 (1.21, 1.64), respectively). Metagenomic predictions of these networks demonstrated enrichment for amino acid biosynthesis pathways.
Both individual and networks of gut microbes were associated with longitudinal multiple sclerosis activity. Known functions and metagenomic predictions of these microbes suggest the important role of butyrate and amino acid biosynthesis pathways. This provides strong support for future development of personalized microbiome interventions to modify multiple sclerosis disease activity.
确定与多发性硬化症随时间变化的活动相关的肠道微生物组特征。
我们使用了 55 名近期诊断为小儿多发性硬化症患者的粪便 16S 核糖体 RNA 测序。微生物组特征包括个体微生物的丰度和来自加权遗传相关网络分析的网络。普伦蒂斯-威廉姆斯-彼得森 Cox 比例风险模型估计了特征与三种疾病活动结果之间的关联：临床复发以及脑 MRI 上新/扩大的 T2 病变和新的钆增强病变。分析调整了年龄、性别和疾病修饰治疗。
参与者平均随访 2.1 年。经过多次测试校正后，有 5 种微生物与所有三种疾病活动结果均具有名义相关性。其中包括丁酸产生菌 Odoribacter（复发风险比 = 0.46，95%置信区间：0.24，0.88）和 Butyricicoccus（复发风险比 = 0.49，95%置信区间：0.28，0.88）。两个肠道微生物共生网络与更高的 MRI 结果风险显著相关（模块 32 和 33 的钆增强病变危险比（95%置信区间）分别为 1.29（1.08，1.54）和 1.42（1.18，1.71）；模块 32 和 33 的 T2 病变危险比（95%置信区间）分别为 1.34（1.15，1.56）和 1.41（1.21，1.64））。这些网络的宏基因组预测显示了氨基酸生物合成途径的富集。
个体和肠道微生物共生网络都与多发性硬化症的纵向活动有关。这些微生物的已知功能和宏基因组预测表明，丁酸和氨基酸生物合成途径起着重要作用。这为未来开发个性化微生物组干预措施以改变多发性硬化症疾病活动提供了有力支持。
