期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：36
页码：22402-22412
DOI：10.1073/pnas.2011703117
出版社：The National Academy of Sciences of the United States of America
摘要：Multiple sclerosis (MS), an autoimmune disease of the central nervous system, generally starts as the relapsing remitting form (RRMS), but often shifts into secondary progressive MS (SPMS). SPMS represents a more advanced stage of MS, characterized by accumulating disabilities and refractoriness to medications. The aim of this study was to clarify the microbial and functional differences in gut microbiomes of the different stages of MS. Here, we compared gut microbiomes of patients with RRMS, SPMS, and two closely related disorders with healthy controls (HCs) by 16S rRNA gene and whole metagenomic sequencing data from fecal samples and by fecal metabolites. Each patient group had a number of species having significant changes in abundance in comparison with HCs, including short-chain fatty acid (SCFA)-producing bacteria reduced in MS. Changes in some species had close association with clinical severity of the patients. A marked reduction in butyrate and propionate biosynthesis and corresponding metabolic changes were confirmed in RRMS compared with HCs. Although bacterial composition analysis showed limited differences between the patient groups, metagenomic functional data disclosed an increase in microbial genes involved in DNA mismatch repair in SPMS as compared to RRMS. Together with an increased ratio of cysteine persulfide to cysteine in SPMS revealed by sulfur metabolomics, we postulate that excessive DNA oxidation could take place in the gut of SPMS. Thus, gut ecological and functional microenvironments were significantly altered in the different stages of MS. In particular, reduced SCFA biosynthesis in RRMS and elevated oxidative level in SPMS were characteristic.
