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Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing
Leyre Mestre1,2, Francisco J Carrillo-Salinas1,3, Ana Feliú1,2
1Neuroimmunology Group, Functional and Systems Neurobiology Department, Instituto Cajal, CSIC , Madrid, Spain.
Abstract:
A growing number of studies support that the bidirectional interactions between the gut microbiota, the immune system and the CNS are relevant for the pathophysiology of MS. Several studies have reported alterations in the gut microbiome of MS patients. In addition, a variety of studies in animal models of MS have suggested that specific members of the gut commensal microbiota can exacerbate or ameliorate neuroinflammation. Probiotics represent oral nontoxic immunomodulatory agents that would exert benefits when using in combination with current MS therapy. Here we investigate the effect of Vivomixx on the gut microbiome and central and peripheral immune responses in a murine model of primary progressive MS. Vivomixx administration was associated with increased abundance of many taxa such as Bacteroidetes, Actinobacteria, Tenericutes and TM7. This was accompanied by a clear improvement of the motor disability of Theiler's virus infected mice; in the CNS Vivomixx reduced microgliosis, astrogliosis and leukocyte infiltration. Notably, the presence of Breg cells (CD19+CD5+CD1dhigh) in the CNS was enhanced by Vivomixx, and while spinal cord gene expression of IL-1β and IL-6 was diminished, the probiotic promoted IL-10 gene expression. One of the most significant findings was the increased plasma levels of butyrate and acetate levels in TMEV-mice that received Vivomixx. Peripheral immunological changes were subtle but interestingly, the probiotic restricted IL-17 production by Th17-polarized CD4+ T-cells purified from the mesenteric lymph nodes of Theiler's virus infected mice. Our data reinforce the beneficial effects of oral probiotics that would be coadjuvant treatments to current MS therapies.
Insights
Vivomixx, a probiotic, improved motor function and reduced neuroinflammation in a mouse model of multiple sclerosis (MS). This study highlights probiotics as potential complementary treatments for MS by modulating the gut microbiome and immune responses.
Area of Science:
- Neuroimmunology
- Microbiome research
- Gastroenterology
Background:
- Bidirectional gut-brain axis interactions are implicated in multiple sclerosis (MS) pathophysiology.
- Alterations in gut microbiota composition are observed in MS patients.
- Gut commensal bacteria can influence neuroinflammation in MS animal models.
Purpose of the Study:
- To investigate the effects of the probiotic Vivomixx on the gut microbiome and immune responses in a murine model of primary progressive MS.
- To assess Vivomixx's impact on neuroinflammation and motor disability.
Main Methods:
- Administration of Vivomixx to Theiler's virus infected mice (a model for MS).
- Analysis of gut microbiome composition, central nervous system (CNS) pathology, and peripheral immune cell populations.
- Measurement of gene expression (IL-1β, IL-6, IL-10) and plasma metabolite levels (butyrate, acetate).
Main Results:
- Vivomixx increased the abundance of specific gut bacterial taxa (Bacteroidetes, Actinobacteria, Tenericutes, TM7).
- Improved motor function, reduced CNS microgliosis, astrogliosis, and leukocyte infiltration were observed.
- Increased regulatory B cells (Breg) in the CNS, diminished IL-1β and IL-6, and enhanced IL-10 gene expression in the spinal cord.
- Elevated plasma butyrate and acetate levels and restricted IL-17 production by Th17 cells.
Conclusions:
- Vivomixx positively modulates the gut microbiome and immune responses in a murine MS model.
- The probiotic demonstrates neuroprotective effects by reducing neuroinflammation and improving motor function.
- Vivomixx shows potential as an adjuvant therapy for MS, complementing current treatments.
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