Abstract
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. We and others have shown that there is enrichment or depletion of some gut bacteria in MS patients compared to healthy controls (HC), suggesting an important role of the gut bacteria in disease pathogenesis. Thus, specific gut bacteria that are lower in abundance in MS patients could be used as a potential treatment option for this disease. In particular, we and others have shown that MS patients have a lower abundance of Prevotella compared to HC, whereas the abundance of Prevotella is increased in patients that receive disease-modifying therapies such as Copaxone® (Glatiramer acetate-GA). This inverse correlation between the severity of MS disease and the abundance of Prevotella suggests its potential for use as a therapeutic option to treat MS. Notably we have previously identified a specific strain, Prevotella histicola (P. histicola), that suppresses disease in the animal model of MS, experimental autoimmune encephalomyelitis (EAE) compared with sham treatment. In the present study we analyzed whether the disease suppressing effects of P. histicola synergize with those of the disease-modifying drug Copaxone® to more effectively suppress disease compared to either treatment alone. Treatment with P. histicola was as effective in suppressing disease as treatment with Copaxone®, whereas the combination of P. histicola plus Copaxone® was not more effective than either individual treatment. P. histicola-treated mice had an increased frequency and number of CD4+FoxP3+ regulatory T cells in periphery as well as gut and a decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4 T cells in the CNS, suggesting P. histicola suppresses disease by boosting anti-inflammatory immune responses and inhibiting pro-inflammatory immune responses. In conclusion, our study indicates that the human gut commensal P. histicola can suppress disease as efficiently as Copaxone® and may provide an alternative treatment option for MS patients.
Highlights
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) and is characterized by the CNS infiltration of inflammatory cells that results in demyelination, axonal damage, and progressive neurologic disability
We have shown that human leukocyte antigen (HLA)-DR3.DQ8 transgenic mice develop severe EAE with significant brain and spinal cord pathology [13] and that EAE could be suppressed by P. histicola in these mice [14]
We examined whether P. histicola and Copaxone R can work in an additive manner to ameliorate disease in a preclinical model of MS to garner evidence for the use of this combined therapy in MS patients
Summary
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) and is characterized by the CNS infiltration of inflammatory cells that results in demyelination, axonal damage, and progressive neurologic disability. Collective evidence suggests that MS is caused by the destruction of the myelin sheath by aberrant T cell-mediated immune responses [1], the etiology and pathogenesis of MS are unknown. The interaction of both genetic and environmental factors likely plays an important role in MS pathogenesis. Genetic factors account for ∼30% of disease risk as determined from studies of identical twins [2], and among these, human leukocyte antigen (HLA) class II genes show the strongest association with disease [3]. Gut bacteria can play an important role in MS pathogenesis and certain gut bacteria showing lower abundance in MS patients can be used as potential treatment option
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