Abstract
Albino Oxford (AO) rats are extremely resistant to induction of experimental autoimmune encephalomyelitis (EAE). EAE is an animal model of multiple sclerosis, a chronic inflammatory disease of the central nervous system (CNS), with established autoimmune pathogenesis. The autoimmune response against the antigens of the CNS is initiated in the peripheral lymphoid tissues after immunization of AO rats with CNS antigens. Subsequently, limited infiltration of the CNS occurs, yet without clinical sequels. It has recently become increasingly appreciated that gut-associated lymphoid tissues (GALT) and gut microbiota play an important role in regulation and propagation of encephalitogenic immune response. Therefore, modulation of AO gut microbiota by antibiotics was performed in this study. The treatment altered composition of gut microbiota in AO rats and led to a reduction in the proportion of regulatory T cells in Peyer’s patches, mesenteric lymph nodes, and in lymph nodes draining the site of immunization. Upregulation of interferon-γ and interleukin (IL)-17 production was observed in the draining lymph nodes. The treatment led to clinically manifested EAE in AO rats with more numerous infiltrates and higher production of IL-17 observed in the CNS. Importantly, transfer of AO gut microbiota into EAE-prone Dark Agouti rats ameliorated the disease. These results clearly imply that gut microbiota is an important factor in AO rat resistance to EAE and that gut microbiota transfer is an efficacious way to treat CNS autoimmunity. These findings also support the idea that gut microbiota modulation has a potential as a future treatment of multiple sclerosis.
Highlights
The origin of adaptive immune system has been associated with establishment of a commensal relation of vertebrates and gut microorganisms [1]
The treatment led to the change in Denaturing Gradient Gel Electrophoresis (DGGE) profile of gut microbiota at week 4, where specific DGGE bands representing core microbiota in Ctrl samples (e.g., Lactobacillus murinus and Lactobacillus intestinalis, Table 1) were absent in samples from Antb-treated rats (Figure 1)
The results of this study show that prolonged oral application of Antb to Albino Oxford (AO) rats modifies their gut microbiota and gut-associated lymphoid tissues (GALT)
Summary
The origin of adaptive immune system has been associated with establishment of a commensal relation of vertebrates and gut microorganisms [1]. It is becoming increasingly appreciated that the immune system is deeply influenced by the gut microorganisms [2] It does not come as a surprise that autoimmunity, as one of the major disorders arising from inappropriate activity of the adaptive immune system, has been tightly connected to gut microbiota perturbations [3]. Based on data obtained from studies on animal models of multiple sclerosis the role of gut microbiota in the initiation of the CNS autoimmunity has been suggested [4]. Discovery of multiple sclerosis-related pathogenic and/or protective gut microbiota organisms or their products would open novel opportunities for diagnosis and therapy of the disease. The latter would rely on antibiotic (Antb) and/or probiotic treatments, as well as on gut microbiota transfer from healthy donors.
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