Decoding the Gut Microbiota in Multiple Sclerosis Using Nanopore Long-Read Sequencing: Insights into Disease Severity and Subtypes.

Abstract

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS), characterized by neuroinflammation and neurodegeneration. Emerging evidence links gut microbiota dysbiosis to immune dysregulation and MS progression. While extensive research has been conducted in Western populations, region-specific studies are needed to assess the influence of local genetic and environmental factors. This study investigates gut microbiota alterations in Egyptian MS patients using Oxford Nanopore sequencing to identify microbial signatures associated with disease progression. Fecal samples from 33 newly diagnosed MS patients (20 with relapsing-remitting MS [RRM] and 13 with Progressive MS [PMS]) and 10 healthy controls were analyzed using long-read Oxford Nanopore sequencing of the full 16S rRNA gene. MS patients exhibited increased microbial richness but reduced evenness, with distinct gut microbiome profiles. Progressive MS was characterized by an abundance of pro-inflammatory bacteria (e.g., Enterococcus faecium and Romboutsia timonensis) and a depletion of short-chain fatty acid (SCFA)-producing species (Ruminococcus bromii and Faecalibacterium duncaniae), potentially contributing to heightened neuroinflammation and disease progression. Relapsing MS exhibited microbial shifts indicative of immune dysregulation, including increased Clostridium saudiense and decreased levels of the gut-protective Faecalibacterium butyricigenerans. Functional analysis linked these microbial alterations to oxidative stress, neurotransmitter imbalance, and suppressed lipid and carbohydrate metabolism. These findings underscore the role of gut microbiota dysbiosis in MS pathogenesis and, by focusing on an underexplored Egyptian cohort, highlight region-specific microbial shifts that may inform targeted therapeutic strategies for both Progressive and Relapsing forms of MS.