Significance: We have compared gut microbiomes in the different stages of multiple sclerosis (MS) based on both microbial and functional analyses using fecal samples. Together with microbial composition data, metagenomic functional and metabolite data revealed a reduced level of microbial butyrate and propionate biosynthesis in the gut of relapsing remitting MS (RRMS). On the other hand, in the gut of secondary progressive MS (SPMS), we revealed an enhancement in microbial DNA mismatch repair, which was consistent with excessive fecal oxidation shown in sulfur metabolomic analysis. As elevated oxidative stress is closely associated with chronic neuroinflammation and neurodegeneration, the present result opens a way to microbiome data-assisted management of MS, useful for prevention of disease progression.

Significance: Multiple sclerosis (MS) can transition from a relapsing-remitting form (RRMS) into a chronic progressive form (secondary progressive MS, SPMS). SPMS pathogenesis remains poorly understood with diagnosis based entirely on retrospective clinical monitoring. We show that T helper cells expressing the transcription factor Eomes (Eomes ⁺ Th cells) were significantly increased in peripheral blood from SPMS patients versus healthy subjects or RRMS and other progressive MS patients. Moreover, Eomes ⁺ Th cells expressing granzyme B were found infiltrating brain tissues in SPMS autopsy samples, providing support for a pathogenic role. Analysis of clinical status on follow-up indicated the value of measuring Eomes ⁺ Th cells for SPMS diagnosis and prognostic monitoring. This study may contribute to future development of biomarker-assisted “precision medicine” for MS.

The aim of this research was to reveal the characteristics of gut microbiome altered by acarbose intervention in Japanese patients with type 2 diabetes (T2D) and its possible association with habitual dietary intake. Eighteen patients with T2D were administered acarbose for four weeks. The abundances of two major phyla, namely Actinobacteria and Bacteroidetes, were reciprocally changed accompanied by the acarbose intervention. There were also significant changes in the abundances of ten genera, including the greater abundance of Bifidobacterium, Eubacterium, and Lactobacillus and the lower abundance of Bacteroides in the group after the intervention than that before the intervention. Hierarchical clustering of habitual dietary intake was performed based on the pattern of changes in the gut microbiota and were classified into distinct three clusters. Cluster I consisted of sucrose, cluster II mainly included fat intake, and cluster III mainly included carbohydrate intake. Moreover, the amount of change in Faecalibacterium was positively correlated with the intake of rice, but negatively correlated with the intake of bread. The intake of potato was negatively correlated with the amount of change in Akkermansia and Subdoligranulum. Acarbose altered the composition of gut microbiome in Japanese patients with T2D, which might be linked to the habitual dietary intake.