Multi-omics of host-microbiome interactions in short- and long-term Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Microbiome

Here, we performed deep multi-omics (shotgun metagenomics of gut microbiota and plasma metabolomics) and clinical phenotyping of healthy controls (n=79) vs. two cohorts of ME/CFS patients - those with short-term disease (10y, n=79). Overall, ME/CFS was characterized by reduced gut microbiome diversity and richness with high heterogeneity, and depletion of sphingomyelins and short-chain fatty acids in the plasma. We found significant differences when stratifying by cohort; short-term ME/CFS was associated with more microbial dysbiosis, but long-term ME/CFS was associated with markedly more severe phenotypic and metabolic abnormalities. We identified a reduction in the gene-coding capacity (and relative abundance of butyrate producers) of microbial butyrate biosynthesis together with a reduction in the plasma concentration of butyrate, especially in the short-term group.

本研究针对健康对照者（n=79）与两队列肌痛性脑脊髓炎/慢性疲劳综合征（Myalgic Encephalomyelitis/Chronic Fatigue Syndrome，简称ME/CFS）患者开展了深度多组学（deep multi-omics）分析，涵盖肠道菌群鸟枪宏基因组学（shotgun metagenomics）与血浆代谢组学（plasma metabolomics），同时完成临床表型分型；其中ME/CFS短期患病组为病程10年患者（n=79）。整体而言，ME/CFS患者以肠道微生物组多样性与丰富度降低、异质性较高为特征，且血浆中鞘磷脂（sphingomyelins）与短链脂肪酸（short-chain fatty acids）含量显著耗竭。按队列分层分析时，我们发现两组存在显著差异：短期患病ME/CFS患者的微生物群失调（microbial dysbiosis）程度更为显著，而长期患病ME/CFS患者则表现出更为严重的表型与代谢异常。我们还检测到微生物丁酸生物合成（butyrate biosynthesis）的基因编码能力（以及丁酸产生菌（butyrate producers）的相对丰度）显著降低，同时血浆丁酸浓度亦随之下降，该现象在短期患病组中尤为突出。