Abstract
The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. Here we use 16S rRNA sequencing to investigate the gut microbiome in subjects with multiple sclerosis (MS, n=60) and healthy controls (n=43). Microbiome alterations in MS include increases in Methanobrevibacter and Akkermansia and decreases in Butyricimonas, and correlate with variations in the expression of genes involved in dendritic cell maturation, interferon signalling and NF-kB signalling pathways in circulating T cells and monocytes. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina, compared with untreated patients. MS patients of a second cohort show elevated breath methane compared with controls, consistent with our observation of increased gut Methanobrevibacter in MS in the first cohort. Further study is required to assess whether the observed alterations in the gut microbiome play a role in, or are a consequence of, MS pathogenesis.
Highlights
The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders
A central nervous system (CNS) autoimmune disease directed against aquaporin-4, there are increased antibodies against gastrointestinal antigens and cross-reactivity to a protein belonging to Clostridium perfringens, suggesting that autoimmunity in neuromyelitis optica may be driven by molecular mimicry against microbial antigens[13]
Faecal samples were collected from 60 multiple sclerosis (MS) patients and 43 healthy controls (Fig. 1); details of the study population are provided in Table 1 and in Methods
Summary
The gut microbiome plays an important role in immune function and has been implicated in several autoimmune disorders. In a relapsing–remitting mouse model of spontaneous EAE, transgenic SJL/J mice raised in germ-free conditions were protected against developing the disease, while the introduction of commensal microbiota into the gut restored susceptibility[6]. While gnotobiotic mice are relatively immunocompromised due to lack of microbial stimulation promoting immune maturation, specific association of germ-free mice with defined commensal species has been shown to modulate the development and severity of EAE. In a study of 20 MS patients versus 40 healthy controls, Faecalibacterium, Prevotella and Anaerostipes were decreased in MS, but the connection between microbiota, treatment and changes in immunity was not examined[11]. If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, there is the potential to develop new diagnostics and therapies to combat the disease
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