Modulation of experimental autoimmune encephalomyelitis through colonisation of the gut with Escherichia coli
J E Libbey1, J M S Sanchez1, B A Fleming2
1Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA.
Abstract:
Multiple sclerosis (MS) is a neuro-inflammatory autoimmune disease of the central nervous system (CNS) that affects young adults. It is characterised by the development of demyelinating lesions and inflammation within the CNS. Although the causes of MS are still elusive, recent work using patient samples and experimental animal models has demonstrated a strong relationship between the gut microbiota and its contribution to CNS inflammation and MS. While there is no cure for MS, alteration of the gut microbiota composition through the use of probiotics is a very promising treatment. However, while most recent works have focused on the use of probiotics to modify pre-existing disease, little is known about its role in protecting from the establishment of MS. In this study, we determined whether colonisation with the probiotic bacterium Escherichia coli strain Nissle 1917 (EcN) could be used as a prophylactic strategy to prevent or alter the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We found that double gavage (two doses) of EcN before induction of EAE delayed disease onset and decreased disease severity. We also found that EcN-treated mice had decreased amounts of perivascular cuffing, CD4+ T cell infiltration into the CNS, together with significantly decreased absolute numbers of Th1 cells, and reduced activation of microglia. Although further studies are necessary to comprehend the exact protective mechanisms induced, our study supports a promising use of EcN as a probiotic for the prevention of MS.
Insights
Probiotic Escherichia coli Nissle 1917 (EcN) may prevent multiple sclerosis (MS). Administering EcN before disease induction delayed onset and reduced severity in an MS preclinical model, suggesting a prophylactic role.
Area of Science:
- Neuroimmunology
- Microbiome research
- Autoimmune diseases
Background:
- Multiple sclerosis (MS) is a CNS autoimmune disease linked to gut microbiota.
- Current MS treatments focus on existing disease, with limited research on prevention.
- Probiotics show potential for modulating gut microbiota and CNS inflammation.
Purpose of the Study:
- To investigate the prophylactic potential of the probiotic Escherichia coli strain Nissle 1917 (EcN) against experimental autoimmune encephalomyelitis (EAE), a preclinical model for MS.
- To determine if EcN administration prior to disease induction can prevent or mitigate EAE development.
- To explore the impact of EcN on key pathological markers associated with MS in the EAE model.
Main Methods:
- Administration of two doses of probiotic Escherichia coli strain Nissle 1917 (EcN) prior to the induction of EAE in a preclinical model.
- Assessment of disease onset, severity, and clinical scores in EAE mice.
- Histopathological analysis of CNS tissue, including evaluation of perivascular cuffing, T cell infiltration (CD4+), Th1 cell populations, and microglial activation.
Main Results:
- Mice receiving prophylactic EcN exhibited delayed onset of EAE and reduced disease severity.
- EcN treatment led to decreased perivascular cuffing and CD4+ T cell infiltration in the CNS.
- Significant reductions in absolute numbers of Th1 cells and microglial activation were observed in EcN-treated mice.
Conclusions:
- Prophylactic administration of Escherichia coli strain Nissle 1917 (EcN) demonstrates a protective effect against the development of experimental autoimmune encephalomyelitis (EAE).
- EcN may serve as a promising probiotic strategy for preventing the onset or progression of multiple sclerosis (MS).
- Further research is warranted to elucidate the precise mechanisms underlying EcN's protective effects in the context of MS.
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