Publicação
Microbiome Intervention to Reduce Experimental Autoimmune Encephalomyelitis Pathogenesis in Middle-Aged Mice
| Resumo: | Multiple Sclerosis (MS) is a chronic autoimmune disease in the central nervous system (CNS), typically manifesting between 20 to 40 years of age, and currently affecting around 2.8 million people worldwide. Its main pathological hallmark is the formation of demyelinated plaques within the CNS, leading to a wide range of symptoms depending on the lesion location. Early episodes often involve optic neuritis and visual loss, while disease progression is frequently associated with cognitive decline, fatigue, depression, ataxia and motor dysfunction (spasticity, weakness, tremors). Other, more systemic symptoms include bladder, bowel and sexual dysfunction, as well as pain. Despite therapeutic advances, MS remains incurable, underscoring the need for novel approaches that target disease progression. Age is a critical risk factor for worsening outcomes, and therapeutic options for older patients remain limited. In addition, growing evidence implicates the gut microbiota as a key modulator of MS pathogenesis through immune and neuroinflammatory mechanisms. In this study, we aimed to investigate whether fecal microbiota transplantation (FMT) from young (3-month-old) naïve mice could attenuate Experimental Autoimmune Encephalomyelitis (EAE), the animal model of MS, in 12-month-old female C57BL/6 mice. Microbiota depletion was achieved with broad-spectrum antibiotics (ABx), followed by FMT and then EAE induction.Our results showed that FMT treatment was capable of reducing the EAE clinical phenotype severity and frailty index, while also improved the motor and cognitive function. Furthermore, spinal cord analysis revealed that microbiota modulation influenced gene expression of neuroimmune pathways, by partially normalizing pro-inflammatory cytokine and chemokine expression, enhanced complement component C1qC, and induce subtle shifts in microglial and innate immune-related genes. Although most changes did not reach statistical significance, these trends suggest that microbial interventions can reshape neuroimmune signaling and contribute to the restoration of immune homeostasis.Overall, these findings highlight the role of the gut microbiota in shapping neuroinflammation and disease severity in aged EAE mice, and support microbiome-based interventions as a promising therapeutic strategy for progressive MS. |
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| Autores principais: | Cabral, Sara Jordão |
| Assunto: | Age EAE FMT Microbiota Multiple Sclerosis Idade EAE FMT Microbiota Esclerose Múltipla |
| Ano: | 2025 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso embargado |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | Multiple Sclerosis (MS) is a chronic autoimmune disease in the central nervous system (CNS), typically manifesting between 20 to 40 years of age, and currently affecting around 2.8 million people worldwide. Its main pathological hallmark is the formation of demyelinated plaques within the CNS, leading to a wide range of symptoms depending on the lesion location. Early episodes often involve optic neuritis and visual loss, while disease progression is frequently associated with cognitive decline, fatigue, depression, ataxia and motor dysfunction (spasticity, weakness, tremors). Other, more systemic symptoms include bladder, bowel and sexual dysfunction, as well as pain. Despite therapeutic advances, MS remains incurable, underscoring the need for novel approaches that target disease progression. Age is a critical risk factor for worsening outcomes, and therapeutic options for older patients remain limited. In addition, growing evidence implicates the gut microbiota as a key modulator of MS pathogenesis through immune and neuroinflammatory mechanisms. In this study, we aimed to investigate whether fecal microbiota transplantation (FMT) from young (3-month-old) naïve mice could attenuate Experimental Autoimmune Encephalomyelitis (EAE), the animal model of MS, in 12-month-old female C57BL/6 mice. Microbiota depletion was achieved with broad-spectrum antibiotics (ABx), followed by FMT and then EAE induction.Our results showed that FMT treatment was capable of reducing the EAE clinical phenotype severity and frailty index, while also improved the motor and cognitive function. Furthermore, spinal cord analysis revealed that microbiota modulation influenced gene expression of neuroimmune pathways, by partially normalizing pro-inflammatory cytokine and chemokine expression, enhanced complement component C1qC, and induce subtle shifts in microglial and innate immune-related genes. Although most changes did not reach statistical significance, these trends suggest that microbial interventions can reshape neuroimmune signaling and contribute to the restoration of immune homeostasis.Overall, these findings highlight the role of the gut microbiota in shapping neuroinflammation and disease severity in aged EAE mice, and support microbiome-based interventions as a promising therapeutic strategy for progressive MS. |
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