Enterotype 3-Driven Gut Dysbiosis: A Primary Pathway to Systemic Inflammation and CNS Autoimmunity in Multiple Sclerosis
| Author | Abolfazl Abdollahi | en |
| Author | Mohammad Ali Jafari | en |
| Author | Nika Shojaei Fard | en |
| Author | Narjes Khatoun Shabani Sadr | en |
| Author | Mehrdad Behmanesh | en |
| Orcid | Abolfazl Abdollahi [0009-0003-8598-5100] | en |
| Orcid | Mohammad Ali Jafari [0009-0007-6941-856X] | en |
| Orcid | Nika Shojaei Fard [0009-0008-3795-4664] | en |
| Orcid | Narjes Khatoun Shabani Sadr [0000-0003-0682-8856] | en |
| Orcid | Mehrdad Behmanesh [0000-0002-3901-304X] | en |
| Issued Date | 2026-03-31 | en |
| Abstract | Context: Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system (CNS) arising from a complex interplay between genetic susceptibility and environmental factors. Evidence Acquisition: Recent evidence has highlighted the gut microbiome as a pivotal environmental modulator. Results: This article proposes a central hypothesis wherein enterotype 3, characterized by a high abundance of destructive mucinolytic bacteria such as Ruminococcus torques, acts as a primary driver of MS pathogenesis. We posit that these bacteria degrade the intestinal mucus layer, leading to increased gut permeability. This breach allows translocation of microbial components like lipopolysaccharide (LPS) into systemic circulation, triggering chronic, low-grade inflammation and skewing the T-cell balance towards a pro-inflammatory Th17 phenotype. In genetically susceptible individuals, this systemic inflammation selectively targets the CNS, initiating autoimmune demyelination. This model reframes MS as a systemic disease with origins in gut dysbiosis, shifting the therapeutic focus from mere CNS-targeted immunosuppression to strategies aimed at restoring gut barrier integrity. Conclusions: Such approaches, including targeted dietary interventions, next-generation probiotics, and enzyme inhibitors, could serve as personalized therapies. By viewing the gut-brain axis as the epicenter of the disease, this framework offers novel avenues for early diagnosis, prevention, and treatment of MS. | en |
| DOI | https://doi.org/10.5812/jjcmb-167241 | en |
| URI | https://brieflands.com/journals/jjcmb/articles/167241 | en |
| Keyword | Multiple Sclerosis | en |
| Keyword | Gut-Brain Axis | en |
| Keyword | Intestinal Permeability | en |
| Keyword | Mucinolytic Bacteria | en |
| Keyword | Gut Microbiome | en |
| Publisher | Brieflands | en |
| Title | Enterotype 3-Driven Gut Dysbiosis: A Primary Pathway to Systemic Inflammation and CNS Autoimmunity in Multiple Sclerosis | en |
| Type | Review Article | en |
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